Facioscapulohumeral dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is a disorder characterized by muscle weakness and wasting (atrophy). The disorder gets its name from muscles that are affected in the face (facio), around the shoulder blades (scapulo), and in the upper arms (humeral). Hamstring and trunk muscles are affected -early on but are less well recognized. Other arm and leg muscles are frequently eventually affected in the course of the disease. Symptoms usually appear before age 20, but can begin in infancy or later in adulthood. Severity of the condition varies widely and some people with the disease allele remain asymptomatic. FSHD is most typically characterized by relatively slow disease progression. Specific symptoms and findings may also vary in range and severity, including among affected members of the same family. Life expectancy is not shortened. FSHD is usually inherited as an autosomal dominant genetic condition.

FSHD may initially involve weakness of muscles of the face, shoulder girdle and arms. Facial weakness may result in limited movements of the lips, causing difficulties whistling, using a straw, or puckering the lips. Affected individuals may also develop a distinctive mask-like facial appearance. Upper facial weakness may also lead to an inability to completely close the eyes during sleep.

FSHD1 is caused by abnormal expression of the DUX4 gene, which is located in the D4Z4 region of chromosome 4. Normally, the DNA in the D4Z4 region is hypermethylated (has many methyl groups: 1 carbon atom and 3 hydrogen atoms) and includes 11-100 repeated segments of DNA. In individuals with FSHD1, this region of chromosome 4 is shortened and contains 1-10 repeats and fewer methyl groups. The lack of methyl groups allows the DUX4 gene to be turned on and produce DUX4 protein in cells and tissues where it is usually not produced, resulting in progressive muscle weakness and atrophy. Generally, a smaller number of repeats is associated with more severe disease.

FSHD appears to affect males and females in relatively equal numbers. The estimated prevalence is between four and ten per 100,000 people.

There are a number of genetic neuromuscular diseases that may be characterized by muscle weakness of varying severity, muscle atrophy, and associated symptoms that may be similar to those that may occur with FSHD. These include some limb girdle muscular dystrophies such as due to calpainopathy and inclusion body myositis. These conditions typically have characteristic features that may differentiate them from FSHD. (For more information on such disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)

FSHD may be diagnosed based upon a thorough clinical examination, identification of characteristic physical findings, a complete individual and family history, and genetic testing. In some affected individuals, laboratory studies may reveal elevated levels of a particular enzyme in the fluid portion of the blood (serum creatine kinase). Tests may also be conducted to record electrical activity in voluntary (skeletal) muscles at rest and during muscle contraction (electromyography [EMG]). Surgical removal (biopsy) and microscopic examination of small samples of muscle tissue is generally not informative in FSHD.


Alexander disease

The symptoms and severity of factor VII deficiency are highly variable; no consistent correlation between the amount of factor VII in the blood and overall severity is seen. Some individuals may not develop any symptoms (asymptomatic), including individuals with relatively low levels of factor VII. Other individuals may have mild cases that are only apparent after trauma or surgery. Mild symptoms can include chronic nosebleeds, easy bruising, and bleeding from the gums. People who menstruate may develop heavy and prolonged periods (menorrhagia).

Factor VII deficiency is caused by mutations of the F7 gene. These mutations are inherited in an autosomal recessive manner. Genetic diseases are determined by the combination of genes for a particular trait that are received from the father and the mother.

Factor VII deficiency affects males and females in equal numbers. The disorder is estimated to affect 1 in 300,000 to 500,000 individuals in the general population. However, many cases of factor VII deficiency go undiagnosed or misdiagnosed, making it difficult to determine the true frequency in the general population. The incidence of factor VII deficiency tends to be higher in countries where marriage to close relatives (consanguineous marriage) is more common. According to the medical literature, more than 200 cases of true factor VII deficiency have been reported. Because of the variable severity of factor VII deficiency, the age of presentation can vary widely from birth until adulthood.

Symptoms of the following disorders can be similar to those of factor VII deficiency. Comparisons may be useful for a differential diagnosis.

A diagnosis of factor VII deficiency is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized blood tests.


Congenital factor X deficiency

Factor X deficiency is a rare genetic blood disorder that causes the normal clotting process (coagulation) to take longer than normal. This causes people to bleed for a longer amount of time spontaneously or after trauma/surgery. Factor X is a clotting protein (also called a clotting factor). Clotting factors are specialized proteins that are essential for proper clotting, the process by which blood clumps together to plug the site of a wound to stop bleeding. Clotting requires a series of reactions to ultimately form a clot to plug a wound. This is referred to as the clotting (coagulation) cascade. The clotting cascade involves different substances in addition to clotting factors. Factor X, which is produced (synthesized) in the liver, eventually interacts with other clotting factors and certain cells or substances, e.g., platelets or fibrinogen, to help to form a clot. Factor X deficiency is caused by a change (variant or mutation) in the F10 gene. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved a drug called Coagadex for adults and children over 12. This medication restores functional factor X levels.

The signs and symptoms of factor X deficiency are highly variable; this means that how the disorder affects one person can be very different from how it affects another person. Symptoms can develop at any age. Generally, the more severe the disorder, the earlier the symptoms begin.

The F10 gene creates (encodes) factor X. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent or overproduced. Variants in the F10 gene result in deficient levels of functional factor X, which in affected individuals, prevents the blood from clotting properly. Depending upon the functions of the protein, this can affect many organ systems of the body. Consequently, affected individuals have difficulty stopping the flow of blood from a wound; but they do not bleed faster or more profusely than healthy individuals.

Factor X deficiency affects males and females and can occur in individuals of any ethnic or racial group. The disorder is estimated to affect about 1 in every 500,000-1,000,000 people in the general population. Rare disorders like factor X deficiency often go unrecognized or misdiagnosed, making it difficult to determine the true frequency in the general population.

Symptoms of the following disorders can be similar to those of factor X deficiency. Comparisons may be useful for a differential diagnosis.

A diagnosis of factor X deficiency is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests.

Treatment of factor X deficiency may require the coordinated efforts of a team of specialists. Pediatricians, general internists, physicians who specialize in diagnosing and treating blood disorders (hematologists), dental specialists and other healthcare professionals may need to plan treatment systematically and comprehensively. Psychosocial support for the entire family is essential as well. Genetic counseling is recommended for affected individuals and their families.


Factor XI Deficiency

In most cases, the bleeding tendency in individuals with factor XI deficiency, even with very low factor levels, is mild. Affected individuals may experience bleeding episodes following trauma or surgery including dental procedures, tonsillectomies or surgery involving the urinary or genital tracts. Bleeding may also occur after circumcision. Bleeding may begin at the time of injury and persist if untreated, or bleeding may develop several hours after the injury. Untreated individuals may develop large, solid swellings of congealed blood (hematomas) following a surgical procedure.

Factor XI deficiency is caused by mutations in the F11 gene. The F11 gene encodes factor XI. Factor XI is one of the essential blood proteins and plays a role in aiding the blood to clot. Mutations of the F11 gene result in deficient levels of functional factor XI. The symptoms of factor XI deficiency occur, in part, due to this deficiency. Individuals with factor XI deficiency often have varying levels of residual factor XI. In many disorders, the amount of residual protein activity correlates with the severity of the disease (e.g. little to no residual protein activity results in severe disease). However, in factor XI deficiency the severity of the disorder does not always correlate with the residual activity of factor XI. For example, individuals with a severe deficiency of factor XI may have mild or no symptoms of the disorder and individuals with a partial deficiency of factor XI may have more significant symptoms. This suggests that additional genetic and environmental factors play a role in the severity of the disorder. This variability even exists among members of the same family.

Factor XI deficiency affects males and females in equal numbers. The disorder can affect individuals of any age and any ethnic group. It is the second most common bleeding disorder to affect women (after von Willebrand disease). The incidence of factor XI deficiency is higher in individuals of Ashkenazi Jewish descent where it is estimated to affect 8% of the population. The severe form of the disorder is estimated to affect approximately 1 in 1,000,000 people in the general population.

Symptoms of the following disorders can be similar to those of factor XI deficiency. Comparisons may be useful for a differential diagnosis.

A diagnosis of factor XI deficiency is based upon identification of characteristic symptoms, a detailed patient and family history, and a thorough clinical evaluation. Several different tests may be necessary to confirm a diagnosis.


Factor XII Deficiency

Factor XII deficiency is rarely associated with any symptoms (asymptomatic). However, when blood from a patient is subjected to a partial thromboplastin time test (PTT), a test measuring clotting time, it takes an abnormally long time for the blood to clot. Serum prothrombin (PT) time, another test of blood clotting, is also abnormally long. The blood level of factor XII tends to vary greatly.

Factor XII deficiency is inherited as an autosomal recessive disorder. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Factor XII deficiency affects persons of Asian descent more often than individuals of other ethnicities. Males and females are affected in equal numbers. Since no symptoms are usually associated with factor XII deficiency, many individuals remain undiagnosed. The exact incidence of the disorder in the general population is unknown, but estimated to be approximately 1 in 1 million individuals.

Symptoms of the following disorders can be similar to those of factor XII deficiency. Comparisons may be useful for a differential diagnosis:

Factor XII deficiency is often diagnosed accidentally during a routine blood clotting (coagulation) tests as in one done before surgery. In affected individuals, it will take longer for their blood to clot during these tests. Further tests can reveal low levels of factor XII in the blood.


Congenital factor XIII deficiency

The symptoms and severity of factor XIII deficiency can vary from one person to another. However, in most of the patients (80%) bleeding symptoms appear after birth with bleeding from the umbilical stump being most common. Some individuals may only have a mild expression of the disorder that will not become apparent until after a bleeding complication occurs following trauma or surgery. In more serious cases, bleeding can occur spontaneously or following activities that normally would not produce problems such as strenuous exercise. It is important to note the variability of factor XIII deficiency and to understand that affected individuals may not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.

Mutations causing factor XIII deficiency are inherited as autosomal recessive traits. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Factor XIII deficiency affects males and females in equal numbers. Symptoms can become apparent at any age. Individuals of any race or ethnicity can be affected. The incidence of factor XIII deficiency has been estimated to be between 1 in 2,000,000-5,000,000 people in the general population. However, factor XIII deficiency can go undiagnosed or misdiagnosed, making it difficult to determine the disorder’s true frequency. Most researchers believe that the disorder is under-diagnosed. The incidence of factor XIII deficiency tends to be higher in countries where marriage to close relatives (consanguineous marriage) is more common.

Symptoms of the following disorders can be similar to those of factor XIII deficiency. Comparisons may be useful for a differential diagnosis.

A diagnosis of factor XIII deficiency is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Standard tests used to diagnose bleeding disorders such as activated partial thromboplastin time (aPTT) and prothrombin time (PT) are normal and therefore ineffective. A diagnosis of factor XIII may be suspected in infants that experience heavy or abnormal bleeding at birth.


Familial adenomatous polyposis

adenomatous polyposis of the colon (APC)

Familial adenomatous polyposis (FAP) is a rare inherited cancer predisposition syndrome characterized by hundreds to thousands of precancerous colorectal polyps (adenomatous polyps). If left untreated, affected individuals inevitably develop cancer of the colon and/or rectum at a relatively young age. FAP is inherited in an autosomal dominant manner and caused by abnormalities (mutations) in the APC gene. Mutations in the APC gene cause a group of polyposis conditions that have overlapping features: familial adenomatous polyposis, Gardner syndrome, Turcot syndrome and attenuated FAP.

Classic FAP is characterized by hundreds to thousands of colorectal adenomatous polyps, with polyps appearing on average at age 16 years. Without colectomy, affected individuals usually develop colorectal cancer by the third or fourth decade of life. FAP is also associated with an increased risk for cancer of the small intestine including the duodenum, and cancer of the thyroid, pancreas, liver (hepatoblatoma), central nervous system (CNS), and bile ducts, although these typically occur in less than 10% of affected individuals.

Familial adenomatous polyposis is caused by germline (present in the first cell of the embryo) mutations in the APC gene and is inherited in an autosomal dominant manner, meaning that on average 50% of children of an affected parent will have the disease passed on to them.

Familial adenomatous polyposis affects males and females in equal numbers. It occurs in approximately one in 5,000 to 10,000 individuals in the United States and accounts for about 0.5% of all cases of colorectal cancer. One estimate suggests that familial adenomatous polyposis affects 50,000 American families. According to national registries, familial adenomatous polyposis occurs in 2.29-3.2 per 100,000 individuals.

Features of the following disorders can be similar to those of the APC gene-associated polyposis conditions. Comparisons may be useful for a differential diagnosis:

Classical FAP is diagnosed clinically when an individual has 100 or more adenomatous colorectal polyps (typically occurring by the third decade of life) or fewer than 100 polyps and a relative with FAP. Genetic testing for mutations in the APC gene is available to confirm the diagnosis of FAP and the associated conditions. Younger individuals may have fewer polyps. A diagnosis is made in younger people by the presence of the typical polyps and in immediate relative with FAP or by genetic testing.


Familial Calcium Pyrophosphate Deposition Disease

The symptoms of CCAL1 and CCAL2 usually begin as acute, recurring attacks of pain, swelling, warmth and redness in one or more joints. Other affected people have swelling, stiffness, and pain with little or no inflammation in the joints.  A knee, wrist, hip, or shoulder is most frequently affected, although any joint of the body may be involved. Acute episodes can last for days to weeks, and symptoms may go away without treatment. CPP deposits may accumulate around the bones of the spine (vertebrae) and cause back or neck pain and/or loss of mobility. Many patients with CPPD develop chronic arthritis which can resemble osteoarthritis or rheumatoid arthritis.

CCAL2 is caused by changes (variants or mutations) in the ANKH gene that lead to an increased amount of the ANKH protein produced.

CCAL1 and CCAL2 are rare disorders. Eight families have been described in the medical literature with CCAL2. Four families with TNFSRF11B gene variants associated with CCAL1 have been identified. There is no known ethnic or sex predilection.

Symptoms of the following disorders can be similar to those of CCAL1 and CCAL2. Comparisons may be useful for a differential diagnosis:

Sporadic CPDD typically occurs in people over age 60 but causes similar symptoms of acute and chronic arthritis. The non-genetic forms may also occur in association with certain metabolic conditions such as hyperparathyroidism, familial hypocalciuric hypercalcemia, Bartter’s syndrome, hypophosphatasia, hypomagnesemia and hereditary hemochromatosis.


Familial cold urticaria

Familial cold autoinflammatory syndrome (FCAS), also known as familial cold urticaria, is a rare, inherited inflammatory disorder characterized by intermittent episodes of rash, fever, joint pain and other signs/symptoms of systemic inflammation triggered by exposure to cold. Onset of FCAS occurs during infancy and early childhood and persists throughout the patient’s life.

Patients with FCAS experience mild to debilitating symptoms such as rash, fatigue, recurrent fever and chills, recurrent joint pain, and recurrent conjunctivitis (inflammation of the outer most layer of the eye causing redness, discomfort and discharge from the eye).

FCAS is usually inherited in an autosomal dominant condition and is caused by a heterozygous mutation in a gene identified as CIAS1/NLRP3 that codes for the protein cryopyrin (NALP3). Mutations in this gene are hypothesized to cause increased activity of a protein complex containing cryopyrin. This protein complex is known as the inflammasome and regulates inflammation in the body. Increased inflammasome activity results in increased release of a protein known as interleukin (IL) 1ß, which leads to symptoms of inflammation such as fever and joint pain.

Since FCAS is a newly discovered condition, the actual incidence and prevalence of the disease is difficult to determine at this time.

Symptoms of the following disorders can be similar to those of FCAS and there is significant phenotypic overlap. Comparisons may be useful for a differential diagnosis.

Diagnosis of FCAS is determined through an evaluation of a patient’s symptoms. Confirmation of the diagnosis is achieved through DNA gene analysis and the identification of a CIAS1/NLRP3 mutation(4), although not all FCAS patients possess a mutation in this gene.


家族性脑病伴神经丝氨酸蛋白包涵体

Familial Encephalopathy with Neuroserpin Inclusion Bodies

familial encephalopathy with Collins bodies

Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a rare genetic degenerative disorder affecting the brain and spinal cord, or central nervous system (neurodegenerative disorder). Affected individuals display poor attention and concentration, declining work or academic performance, and language difficulties. Eventually, they experience a decline in their intellectual abilities (dementia). Memory, however, is relatively well-preserved early in the course of the disease compared to the severe memory deficits that are typical of Alzheimer’s disease. Some affected individuals develop additional symptoms such as uncontrolled, irregular muscle contractions and seizures. Changes in mood, such as apathy, depression, or anger frequently occur. Eventually, affected individuals require comprehensive medical care.

The age of onset, rate of progression, and severity of FENIB varies depending on the specific mutation in the neuroserpin gene. All individuals with a given mutation tend to become symptomatic at approximately the same age and to have similar clinical manifestations. The symptoms of FENIB may become apparent as early as the first decade or as late as the fifth or sixth decade of life. Our knowledge of FENIB is limited by the fact that only a few families with FENIB have been described.

FENIB is caused by changes (mutations) of the serine protease inhibitor 1 (SERPINI1) gene. The SERPINI1 gene contains instructions for creating (encoding) a protein known as neuroserpin. Neuroserpin is normally found in nerve cells and, although its exact function is not fully understood, it is believed to play a vital role in the development, repair, and maintenance of the central nervous system. In FENIB, mutant neuroserpin proteins link together (a process called polymerization) to form long chains that entangle and aggregate. Microscopically, these aggregates are observed as distinct inclusions called Collins bodies within the nerve cells. Collins bodies are believed to disrupt the normal functioning of affected nerve cells, eventually causing the symptoms of FENIB. As the disorder progresses, more Collins bodies are formed and a greater portion of the central nervous system is affected. The relationship between the accumulation and deposition of neuroserpin in the form of Collins bodies in individuals with FENIB and the subsequent development of characteristic symptoms is not fully understood. More research is necessary to determine exactly how Collins bodies may damage or injure nerve cells.

FENIB affects males and females in equal numbers. Only a few families with this disorder have been reported in the medical literature. FENIB was originally described in the medical literature in 1999. The incidence of FENIB in the general population is unknown. The age of onset of FENIB can be as early as the first decade or as late as the fifth or sixth.

Symptoms of the following disorders can be similar to those of FENIB. Comparisons may be useful for a differential diagnosis.

A diagnosis of FENIB may be suspected based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic symptoms and a variety of specialized tests that can rule out other conditions. Such tests may include brain imaging studies such as magnetic resonance imaging (MRI), computed tomography (CT) scans, a test that measures the electrical activity of the brain (electroencephalogram [EEG]), and neuropsychological assessment. The diagnosis of FENIB is usually confirmed by a physician who specializes in the treatment of neurological disorders. The principal confirmatory test is genetic analysis to identify the causative mutation in the SERPINI1 gene or more rarely the identification of Collins bodies in a brain tissue biopsy specimen.


Wells syndrome

Familial eosinophilic cellulitis is a rare skin disorder. It is characterized by raised, red, swollen, and warm areas of skin, in a flame-shaped pattern with associated pain. The exact cause of the disease is unknown. However, bites of spiders, bees, mites, fleas, or ticks (arthropods) are often associated with this skin condition.

Familial eosinophilic cellulitis is a rare skin disorder.  It sometimes occurs as an exaggerated response to bites of spiders, bees, fleas, ticks, or mites (arthropods), or it may have other causes such as surgery or drugs.  The skin of the person will develop flame shaped patterns of raised, swollen, red areas that are warm to the touch.  The episodes usually come on rapidly. Often, familial eosinophilic cellulitis will recur suddenly over a period of years with swelling and redness developing for no apparent reason. The attack may last up to six weeks and may continue to recur for years.

The exact cause of familial eosinophilic cellulitis is still not known.  Some scientists believe that there may be an autoimmune basis for the disorder.  Autoimmune disorders are caused when the body’s natural defenses (antibodies, lymphocytes, etc.), against invading organisms suddenly begin to attack perfectly healthy tissue.

Familial eosinophilic cellulitis affects males and females in equal numbers.  The disorder is more often found in adults, but it may strike children as well.

Symptoms of the following disorders can be similar to those of familial eosinophilic cellulitis.  Comparisons may be useful for a differential diagnosis:

Cellulitis is characterized by inflamed tissue of the skin.  Often the skin becomes red, swollen, and painful, over a large area.  There may be accompanying chills and fever. This disorder can be caused by either Group A beta-hemolytic streptococci, or in older persons it is sometimes caused by Group G streptococci.

Standard treatment of familial eosinophilic cellulitis may consist of administration of steroid drugs. However, the disorder often resolves itself after a number of weeks. Other treatment is symptomatic and supportive.


Familial Hypercholesterolemia

Recent studies have shown that FH is as common as 1 in 250, making it one of the most common genetic diseases. However, most individuals go undiagnosed and most are undertreated given their very high risk. Small subpopulations around the world have a higher incidence, such as Lebanese Christians (1/85), Afrikaners in South Africa (1/72 – 1/100), French Canadians (1/270), and Ashkenazi Jews originating from Lithuania (1/67) known as a founder effect.

A diagnosis of FH can be made using any of the accepted standardized diagnostic criteria described in the Diagnosis section. In instances when a diagnosis of FH is suspected but cannot be definitively confirmed with the available information, genetic testing can often aid in the assessment. In 2019, an international expert panel published a consensus paper supporting the utility of FH genetic testing and a statement that genetic testing should be offered as standard of care.

FH should be considered in an untreated child with LDL-C above 160 mg/dL, or with LDL-C above 130 mg/dL and a positive family history of FH or premature heart disease. In untreated adults, an LDL-C  above 190 mg/dL, a personal and/or family history of early CAD, physical signs such as those described under Symptoms,  or a relative known to have FH, should increase the suspicion of FH


Familial Isolated Hypoparathyroidism

家族性孤立性甲状旁腺功能减退

Familial isolated hypoparathyroidism is a group of rare genetic disorders characterized by parathyroid glands that do not produce or secrete enough parathyroid hormone to maintain normal mineral balance. The parathyroid glands are part of the endocrine system, the network of glands that regulate the chemical processes within the body controlling essential aspects of human development and metabolism throughout the lifespan. Parathyroid hormone plays a vital role in regulating the levels of calcium, magnesium, and phosphorus in the blood. Parathyroid hormone deficiency causes low levels of calcium and magnesium in the blood (hypocalcemia) and high levels of phosphorous.

The symptoms of hypoparathyroidism are predominantly due to low levels of calcium in the blood which lead to neuromuscular irritability and manifested by various symptoms which may include numbness, tingling, spasms (tetany) of the hands, feet, or face, and seizures. Other symptoms include fatigue and muscle weakness. The onset of symptoms of familial hypoparathyroidism is usually during early childhood but can occur at any time from birth to adulthood. Seizures during infancy or childhood may be the first sign of the disorder.

Familial isolated hypoparathyroidism is caused by variants in genes that directly or indirectly control PTH production or secretion. These genetic variants can be inherited in an autosomal dominant, autosomal recessive, or X-linked recessive pattern.1

Familial isolated hypoparathyroidism, with the exception of the X-linked form, affects males and females in equal numbers. The X-linked form affects males almost exclusively. The exact incidence and prevalence of these disorders in the general population is unknown. Some mild cases may go unrecognized, making it difficult to determine the true frequency of these disorders.

Symptoms of the following disorders can be similar to those of familial isolated hypoparathyroidism. Comparisons may be useful for a differential diagnosis.

The diagnosis of familial isolated hypoparathyroidism is made based upon the identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Blood tests should include measurement of intact parathyroid hormone, calcium, phosphorous, and magnesium. Additionally, the measurement of urine mineral levels is important to identify the unusual clinical presentation associated with a heterozygous activating CaSR mutation resulting in familial hypercalciuric hypocalcemia. Urine calcium and magnesium levels are elevated in this disorder. Molecular genetic testing may confirm the diagnosis of hypoparathyroidism. This is an important first step in identifying hypoparathyroidism in family members.

Treatment is aimed at raising calcium levels high enough to provide symptom relief without causing abnormally high levels of calcium excretion in the urine (hypercalciuria). Vitamin D analogs and calcium supplements are the conventional FDA approved therapy for all forms of hypoparathyroidism. The main form of active vitamin D used for individuals with hypoparathyroidism is 1,25 OH vitamin D3, calcitriol. Two other synthetic forms of vitamin D that are often used are cholecalciferol and dihydrotachysterol. These forms of vitamin D have a longer duration of action than calcitriol. Many individuals receive a combination of shorter and longer acting vitamin D analogs.


Familial lipoprotein lipase deficiency

Most cases of familial LPL deficiency are identified during childhood, usually before the age of 10. In approximately 25 percent of patients, the disorder is identified during the first year of life. Some affected individuals may not be identified until adulthood. For example, some women may not be diagnosed until after becoming pregnant or when they begin taking contraceptive medication.

Familial LPL deficiency is caused by changes (mutations) in the LPL gene. The LPL gene contains instructions for creating (encoding) an enzyme known as lipoprotein lipase. This enzyme is essential for the proper breakdown of certain fats in the body. Fat is obtained through the diet and is absorbed by the intestines. It is transported in the form of triglyceride by large lipoproteins known as chylomicrons. (Triglycerides are fatty molecules that are used by the cells of the body for fuel.) When chylomicrons are released into the bloodstream, a protein within chylomicrons called apolipoprotein C2 is activated. This protein is recognized by the enzyme lipoprotein lipase, ultimately resulting in the breakdown of triglyceride. When lipoprotein lipase is inadequate or impaired, chylomicrons accumulate in the plasma, which, in turn, causes abnormal amounts of triglyceride to accumulate in the plasma as well. The accumulation of excess.

Familial LPL deficiency affects males and females in equal numbers. It is estimated to occur in approximately 1 in 250,000 people in the general population and has been described in all races. The prevalence is much higher in Quebec, Canada due to a founder effect. A founder effect is when a small isolated population of settlers (founders) expands over several generations leading to a high prevalence of a particular genetic trait.

Symptoms of the following disorders can be similar to those of familial LPL deficiency. Comparisons may be useful for a differential diagnosis.

A diagnosis of familial LPL deficiency may be suspected based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and certain tests including blood tests.


Familial Mediterranean fever

The symptoms and severity of FMF can vary greatly from one person to another, even among members of the same family.

FMF is caused by changes (disease-causing variants) of the MEFV gene. More than 400 different variants of the MEFV gene have been identified, although only four are clearly disease-causing (pathogenic). They are recorded on a dedicated website https://infevers.umai-montpellier.fr/web/.

FMF can affect individuals of any ethnic group, but the rates are much higher for certain Mediterranean populations including individuals of Armenian, Turkish, Arabic and North African Jewish descent. In these populations, the prevalence is estimated to be 1 in 200.

Symptoms of the following disorders can be similar to those of FMF. Comparisons may be useful for a differential diagnosis.

A diagnosis of FMF is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. These tests can aid in obtaining a diagnosis of FMF or in assessing the extent of the disorder. Prompt diagnosis in FMF is important to avoid misdiagnosis and unnecessary surgery (as many children are misdiagnosed as having appendicitis).


Familial partial lipodystrophy

FPL encompasses several subtypes differentiated by the underlying genetic mutation. The specific symptoms present, severity, and prognosis can vary greatly depending upon the specific type of FPL and the presence and extent of associated symptoms. The specific symptoms and severity can also vary among individuals with the same subtype and even among members of the same family. In addition, some subtypes of FPL have only been reported in a handful of individuals, which prevents physicians from developing an accurate picture of associated symptoms, severity, and prognosis. Therefore, it is important to note that affected individuals will not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms, and overall prognosis.

FPL is caused by mutations of specific genes. So far, mutations in five genes that cause FPL have been identified including the LMNA gene, which causes FPL2, Dunnigan variety; the PPARG gene, which causes FPL3; the PLIN1 gene, which causes FPL4; the AKT2 gene, which cases FPL5; and the CIDEC gene, which causes autosomal recessive FPL. The gene that causes FPL1, Kobberling variety has not been identified. Some individuals with FPL do not have mutations in any of these genes, suggesting that additional, as yet unidentified genes can cause the disorder.

FPL is a rare disorder that has been reported in women more often than in men. This may be due to ascertainment bias because women are more severely affected and more easily recognized. The prevalence of FPL is estimated to be 1 in 1,000,000 people in the general population. However, many cases may go misdiagnosed or undiagnosed, making it difficult to determine the true frequency of the disorder in the general population. The majority of individuals reported in the medical literature have been of European descent. The disorder has also been reported individuals of African and Asian Indian descent.

Symptoms of the following disorders can be similar to those of FPL. Comparisons may be useful for a differential diagnosis.

A diagnosis of FPL is based upon identification of characteristic symptoms, a detailed patient history, and a thorough clinical evaluation. A diagnosis of FPL should be suspected in individuals who lose subcutaneous fat around puberty and gain a muscular appearance. Lipodystrophy, in general, should be suspected in individuals who are lean or non-obese and who present with early diabetes, severe hypertriglyceridemia, hepatic steatosis, hepatosplenomegaly, acanthosis nigricans and/or polycystic ovarian syndrome.


家族性血小板疾病伴相关髓系恶性肿瘤

Familial platelet disorder with associated myeloid malignancy

Familial Platelet Disorder with Associated Myeloid Malignancy

familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML)

Common signs and symptoms of FPD/AML relate to the impact of inherited RUNX1 mutations on platelets and the increased likelihood of developing MDS and/or AML. Platelets are a type of blood cell that are made by specialized cells in the bone marrow (megakaryocytes). Platelets are an important component of our blood and their main function is to help to stop bleeding and form clots. This process is known as hemostasis.

FPD/AML is caused by inherited alterations (mutations) is the RUNX1 gene, located on chromosome 21. The RUNX1 gene is responsible for production of the RUNX1 protein.

FPD/AML is a very rare disorder with an unknown incidence and prevalence. To date, more than 70 FPD/AML families (pedigrees) with inherited RUNX1 mutations have been identified. Patients with FPD/AML have a lifetime risk of approximately 35-40% of developing MDS and/or AML. The average age of onset of MDS or AML is 33 years but has also occurred in patients as young as 6 years and as old as 77 years. Males and females seem to be equally affected and there is no known racial predilection.

Patients with FPD/AML with inherited RUNX1 mutations often have mild to moderately low levels of platelets resulting in symptoms like those seen in immune thrombocytopenia (ITP). ITP is an autoimmune disorder characterized by a low platelet count and symptoms of easy bruising and bleeding. A normal platelet count ranges between approximately 100,000 to 400,000 per microliter of blood. ITP is suspected when a person’s platelet count is persistently below 100,000 per microliter of blood and no other cause has been found. The lower the platelet count, the higher the risk of bleeding. Patients with ITP often present to their doctor with symptoms and signs of bleeding into the skin causing bruising (ecchymosis), small red spots (petechiae), or larger red or purple patches (purpura), or bleeding from the nose (epistaxis), gums, or heavy vaginal bleeding. There are no definitive tests to diagnose ITP so it remains a diagnosis of exclusion, meaning that no other cause for the low platelet count has been found. Treatment of ITP depends on a number of factors including how severe the symptoms are, the platelet count, the patient’s age, the patient’s lifestyle, and personal preferences. (For more information on this disorder, choose Immune Thrombocytopenia as your search term in the Rare Disease Database.)

The diagnosis of FPD/AML is based on clinical suspicion following a thorough clinical history, physical examination, specialized blood tests, and confirmed through genetic testing detecting mutations in the RUNX1 gene. Persons newly diagnosed with AML or MDS, especially at a relatively young age, who have a history of low or abnormally functioning platelets or those with a family history of AML, MDS or other hematologic malignancies such as T-ALL or CMML may be referred for specialist evaluation and genetic testing.


Fanconi anemia

The symptoms of FA vary from person to person. Identified symptoms include a variety of physical abnormalities, bone marrow failure, and an increased risk of malignancy. Physical abnormalities normally reveal themselves in early childhood, but in rare cases diagnoses are made in adulthood. Blood production problems often develop between 6 to 8 years of age. Bone marrow failure eventually occurs in the majority of affected individuals, although the progression and age of onset vary. Patients who live into adulthood are likely to develop head and neck, gynecologic, and/or gastrointestinal cancer at a much earlier age than the general population, whether or not they had earlier blood problems.

The chromosomes within the cells of individuals with FA are unable to repair deoxyribonucleic acid (DNA) damage, and thus break and rearrange easily (chromosome instability). DNA is the carrier of the genetic code and damage to DNA is a normal daily occurrence. In most people, damage to DNA is repaired. However, in individuals with FA, breaks and rearrangements occur more often and their bodies are slow or fail to repair the damage.

The incidence rate of FA is estimated to be about 1 in 136,000 births. This condition is more common among people of Ashkenazi Jewish descent, the Roma population of Spain, and black South Africans.

Symptoms of the following disorders may be similar to those of FA. Comparisons may be useful for a differential diagnosis.

A diagnosis of FA is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings, and a variety of specialized tests.


Fatal Familial Insomnia

The characteristic symptom in FFI is progressive insomnia. Insomnia often begins during middle age, but it can occur earlier or later in life. Insomnia may first be mild, but it then becomes progressively worse until an affected individual gets very little sleep. Insomnia usually begins suddenly and can rapidly worsen over the next few months. When sleep is achieved, vivid dreams may occur. The lack of sleep leads to physical and mental deterioration and the disease ultimately progresses to coma and death.

FFI is caused by an abnormal variant (gene mutation) of the PRNP gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent or overproduced. Depending upon the functions of the protein, this can affect many organ systems of the body, including the brain.

FFI is an extremely rare disorder. The exact incidence and prevalence of the disorder is unknown. The sporadic form of FFI, known as sporadic fatal insomnia (SFI), is extremely rare and has only been described in the medical literature in a few dozen people. Collectively, prion disorders affect 1 to 2 persons per million people in the general population per year. Genetic prion diseases are thought to make up about 15% of all individuals with prion diseases. Because rare diseases often go undiagnosed or misdiagnosed, it is difficult to determine their true frequency in the general population. FFI affects males and females in equal numbers. The average age of onset is 45-50 years old, although the disorder has been described in individuals in their teens and as late as their 70s. FFI has been described in populations around the world.

Symptoms of the following disorders can be similar to those of FFI. Comparisons may be useful for a differential diagnosis.

A diagnosis of FFI is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests.


Felty syndrome

Felty syndrome is usually described as associated with or a complication of rheumatoid arthritis. This disorder is generally defined by the presence of three conditions: rheumatoid arthritis (RA), an enlarged spleen (spenomelgaly) and a low white blood cell count (neutropenia). The presence of RA gives rise to painful, stiff and swollen joints. A low white blood cell count, especially when accompanied by an abnormally large spleen, leads to a greater chance for infections. Other symptoms associated with Felty syndrome may include fatigue, fever, weight loss, and/or discoloration of patches of skin (brown pigmentation). The exact cause of Felty syndrome is unknown. It is believed to be an autoimmune disorder that may be genetically transmitted as an autosomal dominant trait.

The symptoms of Felty syndrome are similar to those of rheumatoid arthritis.  Patients suffer from painful, stiff, and swollen joints, most commonly in the joints of the hands, feet, and arms.  In some affected individuals, Felty syndrome may develop during a period when the symptoms and physical findings associated with rheumatoid arthritis have subsided or are not present.  In this case, Felty syndrome may remain undiagnosed.  In more rare instances, the development of Felty syndrome may precede the development of the symptoms and physical findings associated with rheumatoid arthritis.

The exact causes of Felty syndrome are not clear at this time.  Scientists believe that the blood cell abnormalities, an allergy, or some unknown immunity disturbance may lead to the frequent infections that are commonly associated with this disorder.  These clinicians think that Felty syndrome may be an autoimmune disorder.  Autoimmune disorders occur when the body’s natural defenses (antibodies) against invading or foreign organisms begin to attack the body’s own tissue, often for unknown reasons.

It is estimated that 1 to 3 percent of all patients with rheumatoid arthritis are affected by Felty syndrome.  This is a large number, but most of these go undiagnosed.  The disorder is about three times more common in women than in men.  Felty syndrome is not found as frequently among those of African descent as among Caucasian populations. The disorder generally affects persons 50 to 70 years of age.

The differential diagnosis of Felty syndrome may include sarcoidosis, amyloidosis, reactions to certain drugs, and/or myeloproliferative disorders.  (For more information on these disorders, choose Sarcoidosis or Amyloidosis as your search term in the Rare Disease Database.)

Felty syndrome is usually diagnosed as a result of a thorough clinical evaluation, a detailed patient history, and the identification of the classic triad of physical findings (i.e. the presence of rheumatoid arthritis, low white blood count, and splenomegaly).


Femoral Facial Syndrome

Femoral facial syndrome is a rare disorder characterized by underdeveloped thigh bones (femurs) and unusual facial characteristics. It presents with a very broad range and variety of symptoms. One source lists 31 clinical signs, classified as very frequent, relatively frequent and less frequent.

The exact cause of femoral facial syndrome is not known. Most cases of this disorder occur for no apparent reason (sporadically). However, there have been at least two reported cases of affected relatives that are thought to have been inherited as an autosomal dominant pattern.

Femoral facial syndrome is a very rare disorder that seems to affect more males than females. As of 1993, about 55 patients had been reported and one-third of are associated with maternal diabetes.

Symptoms of the following disorders can be similar to those of femoral facial syndrome. Comparisons may be useful for a differential diagnosis:


HJV or HAMP-related hemochromatosis

Ferroportin disease, also known as hemochromatosis type 4, is a rare genetic disorder characterized by the abnormal accumulation of iron in the body. Ferroportin disease is caused by changes (variants or mutations) of the SLC40A1 gene. The specific symptoms associated with ferroportin disease can vary greatly from one person to another. Some individuals may only have elevated levels of ferritin, a protein that binds to iron and is used as an indicator of the body’s iron stores in the blood plasma. Other individuals may develop symptoms similar to classic HFE-related hemochromatosis.

The symptoms of ferroportin disease vary greatly from one person to another. Researchers believe that different variants in the SLC40A1 gene are associated with different symptoms. Generally, ferroportin disease is separated into two main forms.

Ferroportin disease is caused by variants in the SLC40A1 gene. The SLC40A1 gene contains instructions for creating ferroportin, a specialized protein that is crucial to the proper export of iron from cells. Ferroportin also plays a role in the proper breakdown (metabolism) of iron. Iron is a critical mineral that is found in all cells of the body and is essential for the body to function and grow properly. Iron is found in many types of food including red meat, poultry, eggs and vegetables. Iron levels must remain in a specific range within the body, otherwise they can cause anemia (due to low iron levels) or damage affected organs (due to high iron levels).

Ferroportin disease affects males and females in equal numbers. The exact incidence of ferroportin disease is unknown. Researchers believe that the disorder occurs more frequently than has been reported in the medical literature. Ferroportin affects individuals of all races and ethnicities. Some researchers believe that ferroportin disease is the most common form of hereditary iron overload after classic (type 1 or HFE-related) hemochromatosis.

Symptoms of the following disorders can be similar to those of ferroportin disease. Comparisons may be useful for a differential diagnosis.

A diagnosis of ferroportin disease is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A family history with affected individuals in successive generations is highly suggestive (autosomal dominant inheritance). Blood tests can reveal certain findings associated with ferroportin disease including high levels of ferritin in the blood and, in the milder form of the disease, low or normal saturation of transferrin, another protein that plays a role in the proper transport of iron within the body. Molecular genetic testing for variants in the SLC40A1 gene is available and necessary to confirm the diagnosis.


胎儿和新生儿同种免疫性血小板减少症

Fetal and neonatal alloimmune thrombocytopenia

Fetal and Neonatal Alloimmune Thrombocytopenia

Signs and symptoms of FNAIT vary depending on how low the platelet levels drop in the baby due to increased platelet destruction and reduced platelet production. Signs and symptoms may occur before birth or up to four weeks after birth.

FNAIT occurs when a mother makes antibodies that destroy her baby’s platelets. A mother’s immune system may target her child’s platelets when they contain an antigen inherited from the child’s father that the mother does not have. An antigen is an identifying tag on a cell that all individuals have. The presence of the tag signals the immune system to make antibodies specific to the tag. Those antibodies then turn on the immune system to destroy the foreign cell. When this is the case, the mother’s immune system recognizes her child’s platelets as foreign and mounts an immune response against them. Common platelet antigens in Caucasians with FNAIT are human platelet antigen (HPA)-1a and HPA-5b. Other platelet antigens exist and may include HPA-2, HPA-3, HPA-4 and HPA-15. The mother’s antibodies that attack these antigens are known as anti-HPA antibodies. The HPA-1 antigen is involved in 80-90% of FNAIT cases, and FNAIT associated with anti-HPA-1a antibodies is usually more severe.

FNAIT is the most frequent cause of thrombocytopenia in newborns with an estimated incidence of 1 in 1,500 pregnancies. Fetal intracranial hemorrhage (ICH) associated with FNAIT is estimated to occur in 1 in 10,000 pregnancies.

Other disorders can cause thrombocytopenia in a fetus or newborn. This can occur in autoimmune thrombocytopenia where the mother makes antibodies to her own platelets that may also attack her baby’s platelets if they carry the same antigen as her own. Autoimmune thrombocytopenia can occur when a mother has a disease such as idiopathic thrombocytopenic purpura, systemic lupus erythematosus or hyperthyroidism. Symptoms associated with autoimmune thrombocytopenia are typically milder than those of FNAIT and may include petechiae and purpura that appear several days after delivery.

FNAIT is not routinely screened for during pregnancy and is thought to be underdiagnosed. Babies are screened for FNAIT when they have older siblings who have had it, but for firstborn children with FNAIT, diagnosis is not made until further testing after birth, usually after the baby has developed widespread skin petechiae and thrombocytopenia.

Treatment differs depending on the timing of diagnosis (fetus or newborn). Because of the risk of severe complications like ICH, treatment in a newborn found to have severe thrombocytopenia should begin before diagnostic test results confirm FNAIT.


Fetal hydantoin syndrome

The specific symptoms and physical features associated with fetal hydantoin syndrome can vary greatly from one infant to another. Symptoms may not be noticeable at birth (congenital), but will become apparent as an affected child grows older.

Maternal use of anti-seizure medications such as phenytoin, which is often used to treat epileptic seizures, can result in multiple effects on the developing embryo and fetus, including fetal hydantoin syndrome. The specific amount of phenytoin ingestion required to cause the disorder has not been determined. Phenytoin is often given with other anti-seizure drugs and other (adjunct) medications that may influence development of the disorder. Fetal hydantoin syndrome may be caused by a combination of specific genetic and environmental factors.

Fetal hydantoin syndrome affects males and females in equal numbers. The exact incidence and prevalence of the disorder is unknown. Studies have suggested that approximately 5%-10% of infants exposed to phenytoin during pregnancy will develop fetal hydantoin syndrome.

Symptoms of the following disorders can be similar to those of fetal hydantoin syndrome. Comparisons may be useful for a differential diagnosis.

There is no diagnostic testing that can identify fetal hydantoin syndrome. A diagnosis is made clinically based upon identification of characteristic symptoms in an affected infant in conjunction with a history of phenytoin exposure during gestation. It is important to note that the majority of infants born to women who take phenytoin during pregnancy will not develop fetal hydantoin syndrome.


Fetal Retinoid Syndrome

Fetal retinoid syndrome is a pattern of mental and physical birth defects (congenital malformations) that can result from a mother taking retinoids during pregnancy. The absolute risk of congenital malformations following oral isotretinoin therapy is currently unclear. Overall malformation rates in liveborn infants from prospectively reported pregnancies range from 5% to 20%.

Characteristic features of infants with fetal retinoid syndrome include abnormalities of the craniofacial region, CNS and cardiovascular system. The specific symptoms and physical findings can vary from one infant to another. Affected infants may not have all the symptoms listed below.

Maternal use of synthetic vitamin A (retinoids) such as isotretinoin (Accutane) during pregnancy can result in multiple effects on the developing embryo and fetus including miscarriage, premature delivery and a variety of birth defects. Commercially available isotretinoin brand products include, Absorica, Amnesteem, Claravis, Myorisan and Zenatane; as well as various types of generics available globally.

Fetal retinoid syndrome affects males and females in equal numbers. The exact incidence of fetal retinoid syndrome is unknown and because many children with fetal retinoid syndrome often go unrecognized. The disorder is under-diagnosed, making it difficult to determine the true frequency of the disorder in the general population.

Confirmed diagnosis of fetal retinoid syndrome is made following clinical examination of an affected infant in conjunction with a history of retinoid exposure during pregnancy.


Fetal valproate spectrum disorder

The use of VPA as a single drug (monotherapy) in the first trimester of pregnancy was associated with significantly increased risks of major and minor malformations, including a 20-fold increase in neural tube defects (NTDs) such as spina bifida, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrine disorders, limb defects, and autism as compared with no-use of antiepileptic drugs (AEDs) or with use of other AEDs.

FVS is a rare condition that may occur when a baby is exposed to VPA (brand names include Depakene, depakine, convulex, depakote, encorate, valpakine, etc) during the first trimester. It is believed that VPA crosses the placenta and interferes with normal development causing developmental abnormalities in the fetus (teratogenesis).

FVS affects males and females in equal numbers. There is a 20-fold increase in neural tube defects, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrine disorders, limb defects, and autism, when VPA is used during the 1st trimester of pregnancy compared to no use of antiepileptic drugs.

Fetal abnormalities caused by other antiepileptic drugs may be similar to those of FVS. The determining factor is the identification of the drugs the mother was taking during the first three months of pregnancy.

Fetal hydantoin syndrome is a characteristic pattern of mental and physical birth defects that results from maternal use of the antiepileptic drug phenytoin (Dilantin) during pregnancy. (For more information on this disorder choose Fetal hydantoin syndrome as your search term in the Rare Disease Database.)


FG Syndrome Type 1

FG syndrome type 1 (FGS1) is an X-linked genetic disorder that is characterized by poor muscle tone (hypotonia), intellectual disability, constipation and or anal anomalies and complete or partial absence of the part of the brain that connects the two hemispheres of the brain (corpus callosum). Other features of the disorder are small and simple ears, tall and prominent forehead, wide and flat thumbs and great toes and down slanting eyes. FGS1 is an X-linked genetic disorder typically caused by a change (variant or mutation) in the MED12 gene. The spectrum of disorders caused by variants in this gene is still being defined. Some individuals previously diagnosed with FGS1 do not have a MED12 gene variant and, therefore, probably have a different reason for intellectual disability.

FG syndrome type 1 (FGS1) is an X-linked genetic disorder that is characterized by poor muscle tone (hypotonia), intellectual disability, constipation and or anal anomalies and complete or partial absence of the part of the brain that connects the two hemispheres of the brain (corpus callosum). Other features of the disorder are small and simple ears, tall and prominent forehead, wide and flat thumbs and great toes and down slanting eyes. Additional features may include a large head (macrocephaly), widely spaced eyes (ocular hypertelorism) and upswept frontal hair. Seizures and congenital heart defects have also been reported.

FGS1 is typically caused by a variant in the MED12 gene on the X chromosome located at Xq13.1. The MED12 gene is responsible for production of the MED12 (TRAP230) protein that is involved in the regulation of transcription.

The prevalence of FGS1 is unknown. The spectrum of disorders caused by variants in this gene is still being defined. Some individuals previously diagnosed with FGS1 do not have a MED12 gene variant and, therefore, probably have a different reason for intellectual disability.

Symptoms of the following disorders can be similar to those of FGS1 syndrome. Comparisons may be useful for a differential diagnosis:

Lujan syndrome is an X-linked genetic disorder in the spectrum of disorders caused by variants in the MED12 gene. This condition is characterized by intellectual disability, hypotonia, large head, tall and thin body, long and thin face and high and narrow palate. Additional features that may be present include small jaw, long hands with hyperextensible digits, abnormalities of the corpus callosum and nasal speech.


Fibrillary Glomerulonephritis

The most common symptoms of fibrillary glomerulonephritis include:

The causes of fibrillary glomerulonephritis are currently unknown and are being researched. Antibodies (immunoglobulins) build up in the glomerulus, often in patients with an underlying disease such as cancer (particularly leukemia, lymphoma and multiple myeloma), a monoclonal gammopathy or an autoimmune disease (Crohn’s disease, Graves’ disease, immune thrombocytopenia, etc.).

Patients with a history of cancer (particularly leukemia or multiple myeloma), a monoclonal gammopathy or an autoimmune disease (particularly Crohn’s disease, lupus, Graves’ disease, or immune thrombocytopenia [ITP]) are at risk for fibrillary glomerulonephritis.

Immunotactoid glomerulopathy – a similar disease in which antibodies (immunoglobulins) and microtubules affect the glomerulus rather than fibrils.

A diagnosis is made from a kidney biopsy to look at the fibrils under an electron microscope and immunofluorescence microscope. Routine lab tests may detect the blood and protein in the urine, but a biopsy is the only way to determine which proteins are affecting the glomerulus.


Fibrodysplasia ossificans progressiva

进行性骨化性纤维发育不全

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare genetic connective tissue disorder characterized by the abnormal development of bone in areas of the body where bone is not normally present (heterotopic ossification), such as the ligaments, tendons and skeletal muscles. Specifically, this disorder causes the body’s skeletal muscles and soft connective tissues to undergo a metamorphosis, essentially a transformation into bone, progressively locking joints in place and making movement difficult or impossible. Patients with FOP have malformed big toes that are present at birth (congenital). Other skeletal malformations may occur. The abnormal episodic development of bone at multiple soft tissue sites leads to stiffness in affected areas, limited movement and eventual fusion (ankylosis) of affected joints (neck, back, shoulders, elbows, hips knees, wrists, ankles, jaw – often in that order).

All individuals with classic FOP have malformations of the great toes and, in approximately 50% of patients, the thumbs. These changes in the skeleton are present at birth (congenital) and are the first clinical signs of this disorder. The most common skeletal malformation associated with FOP is a shortened great toe with a malformed distal first metatarsal and a missing or abnormal first phalanx and/or interphalangeal joint. Other malformations of the toes and fingers may include inward turning of the great toe toward the other toes (hallux valgus), abnormally short fingers and toes (microdactyly) and/or permanent fixation of the fifth finger in a bent position (clinodactyly). Other congenital signs of FOP include proximal medial tibial osteochondromas, malformation of the upper part of the spinal column (cervical vertebrae) and an abnormally short broad neck of the bone in the thigh that extends from the knee to the pelvis (femur).

Most cases of FOP occur sporadically, and there is a single affected individual within a family. When a familial pattern has been identified, FOP is inherited in an autosomal dominant pattern.

FOP is a very rare inherited connective tissue disorder that was first identified in the 18th century. The prevalence of FOP is estimated to be 1/1,000,000. FOP affects males and females equally, and people from all ethnicities.

Symptoms of the following disorders may be similar to those of fibrodysplasia ossificans progressiva. Comparisons may be useful for differential diagnosis:

Aggressive juvenile fibromatosis is a condition in which cells called fibroblasts increase in number in tendons, ligaments and other connective tissues. This overgrowth of cells may invade adjacent tissues, causing pain and disability. The resulting lesions may resemble the tissue swelling associated with FOP. However, individuals with aggressive juvenile fibromatosis do not have the toe malformation that is associated with FOP, nor do they develop heterotopic ossification.


Fibrolamellar Carcinoma

Fibrolamellar carcinoma is a rare form of cancer that affects the liver. Unlike most cancers of the liver, it occurs with greater frequency in adolescents and young adults who are otherwise healthy. There are often no symptoms or signs of the disorder for a long time. Symptoms that can develop include abdominal pain, unintended weight loss, and a general feeling of poor health (malaise). Treatment is usually through surgical removal (resection) of the tumor. When surgery is not possible or is unsuccessful, then other therapies may be considered. Recurrence following successful surgical removal of a tumor can occur, meaning that sometimes the tumor can come back after it was removed. The exact, underlying cause of this disorder is unknown.

The signs and symptoms usually arise with advanced disease. For many years, affected individuals may not have any noticeable signs or symptoms (asymptomatic) because they are otherwise healthy. Initial symptoms are nonspecific, which means they can be seen in a variety of different medical conditions. Every person is unique and how this disorder affects one person can be different from how it affects another person. Fibrolamellar carcinoma may not cause problems for many, many years or it can be aggressive, quickly spreading locally or spreading to other parts of the body (metastasizing).

As with many forms of cancer, the exact, underlying cause of fibrolamellar carcinoma is unknown. Researchers speculate that multiple factors including genetic and environmental ones play a role in the disorder’s development. Current research suggests that abnormalities of DNA (deoxyribonucleic acid), which is the carrier of the body’s genetic code, are the underlying basis that causes cells to become malignant.

Fibrolamellar carcinoma is an ultra rare form of cancer. It affects both men and women and affects approximately 1 in 5,000,000 people in the general population.  Fibrolamellar carcinoma occurs with greater frequency among young adults with a median age of diagnosis of 25. It is found all over the world and the rate of occurrence can vary geographically. The disorder accounts for about 1% of all people with primary liver cancer in the United States, but accounts for about 5.8 percent of all people with primary liver cancer in Mexico.

Symptoms of the following disorders can be similar to those of fibrolamellar carcinoma. Comparisons may be useful for a differential diagnosis.

A diagnosis of fibrolamellar carcinoma is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation, and a variety of specialized tests. A diagnosis of fibrolamellar carcinoma can be difficult because symptoms may be nonspecific and can be caused by many different types of disorders. Because the disorder occurs in young adults, a diagnosis of cancer is usually not suspected initially until many other more common conditions are ruled out.


Fibromuscular Dysplasia

欧洲非罕见：动脉肌纤维发育不良

Fibromuscular dysplasia, commonly called FMD, is a disease that causes one or more arteries in the body to have abnormal cell development in the artery wall. As a result, areas of narrowing (stenosis), aneurysms, or tears (dissection) may occur. If narrowing or a tear causes a decrease in blood flow through the artery, symptoms may result. FMD is most commonly found in the arteries that supply the kidneys with blood (renal arteries) and the arteries called the carotid and vertebral arteries which are found in the neck and supply the brain with blood. Less commonly, FMD affects the arteries in the abdomen (supplying the liver, spleen and intestines) and extremities (legs and arms). In more than one-half of people with this disease, there will be evidence of FMD in more than one artery.

Some people with this disease do not have symptoms or findings on a physical examination. The signs and/or symptoms that a person with FMD may experience depend on the arteries affected and whether there is narrowing, tears, or aneurysms within them. Any pain or clinical sign related to FMD typically comes from the organ that is supplied by that artery. For example, FMD in the kidney arteries may cause high blood pressure. FMD in the carotid arteries may cause headaches or a swooshing sound in the ears (called pulsatile tinnitus). Some patients with FMD may have no symptoms at all but are diagnosed with this disease when a physician hears a noise over one of the arteries due to disturbed or turbulent blood flow within the vessel. This noise is known as a bruit.

The cause of FMD is not yet known, but several theories have been suggested. A number of case reports in the literature have identified the disease in multiple members of the same family including twins. As a result, it is felt that there may be a genetic cause. However, a relative may have different artery involvement, different disease severity, or not develop FMD at all. In fact, most individuals with FMD do not have a family member who also has the disease. Among some individuals with FMD, there is a family history of other vascular problems, such as blood vessel aneurysms.

FMD affects women far more commonly than men, although men and children can be affected with this disease. In children with FMD, the disease seems to more commonly present with significant narrowing rather than tears of arteries and also seems to involve the arteries to the kidneys and intestines more commonly than the carotid vessels. In the pediatric population, FMD affects both boys and girls.

The vascular subtype of Ehlers-Danlos syndrome (type IV) has been associated with the most common type of fibromuscular dysplasia, known as multifocal FMD. This syndrome should be suspected in patients with multiple aneurysms and/or tears (dissections) in arteries in addition to the typical angiographic findings of fibromuscular dysplasia. There have been isolated reports of fibromuscular dysplasia associated with other disorders, including Alport syndrome, pheochromocytoma, Marfan syndrome, and moyamoya disease. (For more information on these disorders, search for the term in the Rare Disease Database.)

In order to diagnosis FMD, a test must be done to image the blood vessels. There are many options for imaging the arteries, including specialized blood vessel ultrasound known as duplex ultrasound; a CAT scan of the arteries which is obtained after a dye is given through the veins, or a special type of MRI. In many cases, the diagnosis of FMD requires that a procedure known as an arteriogram be performed. Arteriography is a procedure that is performed by a radiologist, vascular surgeon, cardiologist, or vascular medicine specialist with appropriate training. It involves inserting a wire into or near the affected artery and injecting contrast material, a dye that can be detected by an X-ray machine. An X-ray of the affected area is then taken and examined. The individual is usually awake during an arteriogram procedure although medications may be given to keep her or him comfortable. This outpatient procedure usually lasts from one to two hours with a recovery period of up to six hours (this varies widely).


IgG4-related mediastinitis

Fibrosing mediastinitis (FM) is a rare disease characterized by dense invasive fibrotic infiltration of the mediastinum (middle portion of the chest, situated between the lungs) and/or hilar regions (areas between the upper and lower lobes of each lung) of the chest causing narrowing or occlusion of important chest structures, including pulmonary arteries, pulmonary veins, the superior vena cava, airways/bronchi, or the esophagus. Because of the vital nature of these structures, this slowly progressive disease is associated with significant morbidity and can be fatal if it affects both lungs.

Typically, people with PHFM were originally exposed/infected with H. capsulatum as children but the symptoms begin in most patients in the third or fourth decade of life. No evidence suggests an association with specific ancestry or gender. Patients may present with shortness of breath (dyspnea), fatigue or loss of stamina, cough with blood (hemoptysis) or without, chronic chest (pleuritic) pain, recurrent pulmonary infections or pneumonias, difficulty swallowing (dysphagia), or swelling of the arms and face. These symptoms most commonly occur because there is an occlusion or critical narrowing of one of the main vessels in the chest, such as the superior vena cava (the vein which returns blood from the head, neck, and arms the heart), pulmonary arteries, and/or pulmonary veins. Superior vena cava (SVC) syndrome, characterized by face and arm swelling due to obstruction of the vena cava, is a common symptom. Some patients do not develop this syndrome despite having obstruction of the SVC because collateral alternative veins (sometimes visible on the anterior chest) enlarge sufficiently to bypass the SVC as it becomes slowly obstructed and successfully return blood to the heart. Cough and shortness of breath are the most common symptoms when obstruction of a central airway occurs. Pulmonary venous obstruction usually presents with shortness of breath, coughing blood, or sometimes collection of fluid in the space between the lung and the chest wall (pleural effusion). Symptoms can be present for years before diagnosis.

In the majority of patients, FM is triggered by the body’s abnormal excessive immune reaction to prior exposure to Histoplasma capsulatum, a fungus found in soil in endemic areas, most notably along the Mississippi and Ohio River valleys in the United States. The fungus resides in the soil, becomes airborne when the soil is disturbed, and is subsequently inhaled. Histoplasma is also associated with bird and bat droppings, the former of which do not appear to become infected by the fungus but may carry the fungus on their feathers, while the GI tracts of the latter may become colonized with the fungus.

Of the entire population who are exposed to Histoplasma, only a tiny fraction (far fewer than 1%) develop the excessive response to the fungal infection that is the basis of PHFM. Of the many millions of people with repeated exposures to Histoplasma while living in endemic areas, the vast majority never develop symptomatic histoplasmosis, and far fewer go on to develop PHFM. It is estimated that there are only a few hundred cases of PHFM in the United States. At Vanderbilt University Medical Center, a referral center for this condition in an endemic area, approximately 10 new cases have been evaluated annually over the last few decades. PHFM is seen only in individuals who lived in an endemic region sometime during their life. Idiopathic FM is believed to be even rarer, with an estimated several dozen cases known in the United States.

Symptoms of the following disorders can be similar to, or caused by, FM. Others may have a similar radiographic appearance as FM leading to misdiagnosis. Understanding of each condition may be critical for correct diagnosis.

Diagnosing either form of FM is best accomplished by chest CT, a scan that shows the abnormal tissue in the mediastinum. The characteristic appearance of a mediastinal abnormality on chest CT scan in a person who has lived in a region with endemic histoplasmosis can definitively diagnose PHFM in many cases, especially when assessed by a pulmonologist or radiologist with expertise in this disease.


Fabry disease

The severity and specific symptoms of FD can vary greatly from one person to another. Most affected individuals only have one bone involved and often there are no associated symptoms (asymptomatic). Many times, FD is discovered incidentally when x-rays are performed for another reason. Conversely, some affected individuals can have multiple bones affected and develop severe and potentially disabling or disfiguring symptoms. In most affected individuals, onset of symptoms is usually in childhood; it is unusual for the onset of the disorder to occur after 10.

The underlying cause of FD is not fully understood. Researchers believe that the disorder is caused by a change (mutation) in a gene called GNAS1. This gene mutation occurs after fertilization of the embryo (somatic mutation) and is therefore not inherited, nor will affected individuals pass the mutation on to their children. Affected individuals have some cells with a normal copy of this gene and some cells with the abnormal gene (mosaic pattern). The variability of symptoms of FD is due, in part, to the ratio of healthy cells to abnormal cells. Researchers do not know why these somatic mutations occur; they appear to develop randomly for unknown reasons (sporadically).

Fibrous dysplasia affects males and females in equal numbers. The disorder is diagnosed earlier in children and young children. The exact incidence and prevalence of the disorder is unknown. Mild cases may go undiagnosed, making it difficult to determine the true frequency of FD in the general population. The monostotic form is more common than the polyostotic form; according to some reports by a ratio of 4:1.

Symptoms of the following disorders can be similar to those of fibrous dysplasia. Comparisons may be useful for a differential diagnosis.

A diagnosis of fibrous dysplasia is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Individuals with mild forms of monostotic FD may be diagnosed incidentally when receiving an x-ray for another reason.


Filariasis

Filariasis is an infectious tropical disease caused by any one of several thread-like parasitic round worms. The two species of worms most often associated with this disease are Wuchereria bancrofti and Brugia malayi. The larval form of the parasite transmits the disease to humans by the bite of a mosquito. In the early stages of the infection, the patient characteristically complains of fever, chills, headaches and skin lesions. Any one of several antiparasitic agents may be effective in eliminating the worm. However, if the disease is left untreated, obstruction of the lymph flow will cause particular areas of the body especially the legs and external genitals, to swell profoundly. Symptoms are primarily a response to adult worms that cause inflammation. Chronic inflammation may progress to hardening of the lymphatic vessels (fibrosis) and obstruction of the lymph flow.

Some people with filariasis have no symptoms.  Other affected individuals may have episodes of acute inflammation of lymphatic vessels (lymphangitis) along with high temperatures, shaking chills, body aches, and swollen lymph nodes.  Excessive amounts of fluid may accumulate (edema) in the affected areas (i.e., arms and/or legs), but the accumulation typically resolves after the other symptoms are gone.  Attacks may also be accompanied by acute inflammation of the genitalia leading, in males, to inflammation, pain and swelling of the testes (orchitis), sperm track (funiculitis), and/or sperm ducts (epididymitis).  The scrotum may become abnormally swollen and painful.

Filariasis is a rare infectious tropical disorder caused by the round worm parasites (nematode) Wuchereria bancrofti or Brugia malayi.  Symptoms result primarily from inflammatory reactions to the adult worms.  Some people may also develop hypersensitivity reactions to the small larval parasites (microfilariae).

Filariasis is common disease in tropical regions of the world.  The organism W. bancrofti is present throughout Africa, Asia, China, and South America. B. malayi is found in southern and southeast Asia.  Filariasis is extremely rare in North America and occurs only when these organisms are imported from tropical regions.  The infection is transmitted by several different types of tropical mosquitos which transfer the larval stage of the organism (microfilariae) from one host to another. Lymphatic filariasis affects about 120 million people worldwide.  Short-term travelers to areas where it is endemic are at low risk for this infection.  People who visit endemic areas for extended periods of time, and especially those who are in areas or situations in which they are intensely exposed to infected mosquitoes, can become infected.  Most infections seen in the U.S. are in immigrants from endemic countries, according to the Centers for Disease Control and Prevention (CDC).

Symptoms of the following disorders can be similar to those of Filariasis. Comparisons may be useful for a differential diagnosis:

Acanthocheilonemiasis is a tropical infectious disease caused by a multicellular parasite (filarial worm [nematode]), called Acanthocheilonema perstans.  This parasite is found most commonly in Africa.  Initially people with Acanthocheilonemiasis may have no symptoms.  Symptoms may include itchy skin (pruritis), abdominal pain, chest pain, muscle pain (myalgias), and/or areas of swelling under the skin.  Other symptoms may include an abnormally enlarged liver and spleen (hepatosplenomegaly), and inflammation in the affected organs.  (For more information on this disorder, choose Acanthocheilo as your search term in the Rare Disease Database.)


Filippi syndrome

Syndactyly Type I with Microcephaly and Mental Retardation

Filippi syndrome is an extremely rare genetic disorder that may be apparent at birth (congenital). The disorder is characterized by an unusual facial appearance, abnormalities of the fingers and toes, and mild to severe mental retardation. Primary physical findings include growth delays, webbing or fusion (syndactyly) of certain fingers and toes, inward deviation or bending (clinodactyly) of the fifth fingers (pinkies) and microcephaly, condition that indicates that the head circumference is smaller than would be expected for an infant’s age and sex. Filippi syndrome is transmitted as an autosomal recessive trait.

Filippi syndrome is characterized by growth delays before and after birth (prenatal and postnatal growth retardation), a low birth weight, and short stature. Affected individuals also have characteristic abnormalities of the head and facial (craniofacial) area, resulting in a distinctive facial appearance. Affected infants may often exhibit microcephaly, condition that indicates that the head circumference is smaller than would be expected for an infant’s age and sex

Filippi syndrome is transmitted as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Filippi syndrome is a rare genetic disorder that appears to affect males and females equally. Since the disorder was originally described in 1985 (G. Filippi), approximately 18 cases have been reported in the medical literature, including affected siblings within certain families (kindreds) as well as isolated cases.

Symptoms of the following disorders may be similar to those of Filippi syndrome. Comparisons may be useful for a differential diagnosis:

KBG syndrome is a rare genetic disorder characterized by mild to moderate mental retardation and speech defects, abnormalities of the head and facial (craniofacial) area, short stature, and additional skeletal malformations.  Characteristic facial features include a relatively round face and short head (brachycephaly); broad eyebrows that grow together across the base of the nose (synophrys); a high nasal bridge; bow-shaped lips; and prominent ears.  In addition, certain teeth may be abnormally large (macrodontia) whereas others may be absent (oligodontia).  Skeletal abnormalities may include delayed bone age; abnormal shortness of certain bones of the fingers; webbing or fusion (syndactyly) of the second and third toes; or malformations of bones within the spinal column (vertebrae).   KBG syndrome is inherited as an autosomal dominant trait.  (For further information, choose KBG as your search term in the Rare Disease Database.)


Floating Harbor Syndrome

Although researchers have been able to establish a clear syndrome with characteristic or core symptoms, much about the disorder is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorder prevent physicians from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.

Floating-Harbor syndrome is caused by a mutation in the SRCAP gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.

Floating-Harbor syndrome affects males and females in equal numbers. The exact incidence and prevalence of the disorder is unknown. Because cases may go undiagnosed or misdiagnosed, determining the true frequency of FHS in the general population is difficult. As of 2014, approximately 100 cases have been reported in the medical literature. However, some of these individuals do not fit the classical description of FHS and were found not to carry mutations in the SRCAP gene.

Symptoms of the following disorders can be similar to those of Floating-Harbor syndrome. Comparisons may be useful for a differential diagnosis.

A diagnosis of Floating-Harbor syndrome is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. The distinctive facial features that characterize FHS can be subtle and difficult to recognize during infancy. Additionally, many of the other symptoms are nonspecific to FHS, making it difficult to diagnose the disorder on clinical grounds alone.


Focal dermal hypoplasia

Focal dermal hypoplasia (FDH), also known as Goltz syndrome, is a rare multisystem disorder that principally involves the development of the skin, hands and feet and eyes. It is a type of ectodermal dysplasia, a group of heritable disorders causing the hair, teeth, nails and glands to develop and function abnormally. Most of the cases of FDH (about 90 percent) are seen in females. This disorder is characterized by skin abnormalities that develop into streaks or lines of tumor-like lumps on various parts of the body. This syndrome displays a wide array of symptoms and may affect almost any organ. FDH is caused by changes (variants or mutations) or duplications/deletions in the PORCN gene.

An extremely wide range of symptoms characterizes FDH.

FDH is caused by changes (variants or mutations) in the PORCN gene that creates proteins important in the development of the skin, skeleton and eyes in a developing embryo and fetus. Recent studies of patients with symptoms consistent with FDH have found genetic changes in the PORCN gene in nearly all affected females.

Prevalence estimates are not available for FDH. Approximately 200 to 300 affected individuals have been reported worldwide, and only about 10 percent are live born males.

Symptoms of the following disorders can be similar to those of focal dermal hypoplasia. Comparisons may be useful for a differential diagnosis:

Ectodermal dysplasias are a group of hereditary, non-progressive skin diseases in which the affected tissue derives primarily from the ectodermal germ layer. The skin, its derivatives, and some other organs are involved. Symptoms may include eczema, poorly functioning sweat glands, sparse or absent hair, abnormal hair, disfigured nails and difficulty with the nasal passages and ear canals. (For more information on these disorders, choose ectodermal dysplasias as your search term in the Rare Disease Database.)


Focal Segmental Glomerulosclerosis

弃用：家族性激素敏感型原发性肾病综合征伴局灶性节段性透明样变性

Focal segmental glomerulosclerosis (FSGS) is a term for a specific pattern of damage to the kidneys. The kidneys are two bean-shaped organs in the body, one on each side of the body just below the rib cage in the back. The kidney has multiple functions including filtering the blood of waste products and other substances and producing urine to carrying waste from the body. FSGS occurs when the filters of the kidney, which are made of clusters of tiny blood vessels (capillaries) and known as renal glomeruli, become scarred or hardened (sclerosis). Each kidney has about a million glomeruli, which are part of a larger structure called the nephron; the nephron is the basic unit of the kidneys. The glomeruli help to filter out waste products and extra fluid from the blood. Scarring or damage to the glomeruli can lead to an inability of the kidneys to process waste products and eliminate those waste products from the body through the urine. Ultimately, these abnormalities lead to progressive kidney damage including decreased function and efficiency of the kidneys, and potentially kidney failure. There are different causes of FSGS and, in some instances, the cause is unknown. Depending on the cause, FSGS may be treated with certain medications, but sometimes despite treatment affected individuals will eventually require dialysis or a kidney transplant.

The signs and symptoms of focal segmental glomerulosclerosis are related to progressive damage to the kidneys. Some people may not have any noticeable symptoms (asymptomatic), while others may have progressive disease that can, often rapidly, result in kidney failure.

There are many different causes for FSGS. Many researchers believe that FSGS is caused by damage to a specialized kidney cell in the glomerulus (filter) called the podocyte. Abnormalities in the health, function, or number of podocytes ultimately leads to the scarring (sclerosis) of the glomeruli that characterizes FSGS.

Focal segmental glomerulosclerosis is estimated to affect about 7 people per million people in the general population, although specific incidence rates vary in different populations. FSGS accounts for about 40% of adults with nephrotic syndrome and about 20% of children with nephrotic syndrome. In the United States, FSGS accounts for 5%-20% of all people who experience end stage renal disease. Some recent studies have found that the number of people who have FSGS is increasing each year.

Symptoms of the following disorders can be similar to those of focal segmental glomerulosclerosis. Comparisons may be useful for a differential diagnosis.

A diagnosis of focal segmental glomerulosclerosis is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. To confirm the diagnosis, small pieces of kidney tissue are sampled in a procedure called a kidney biopsy. These tissue samples are evaluated under a microscope to look for the signs of FSGS.


Follicular Lymphoma

Follicular lymphoma is a form of cancer. It is a type of non-Hodgkin lymphoma (NHL), which is a group of related cancers that affect the lymphatic system (lymphomas). The lymphatic system functions as part of the immune system and helps to protect the body against infection and disease. It consists of a network of tubular channels (lymph vessels) that drain a thin watery fluid known as lymph from different areas of the body into the bloodstream. Lymph accumulates in the tiny spaces between tissue cells and contains proteins, fats, and certain white blood cells known as lymphocytes. As lymph moves through the lymphatic system, it is filtered by a network of small structures known as lymph nodes that help to remove microorganisms (e.g., viruses, bacteria, etc.) and other foreign bodies. Groups of lymph nodes are located throughout the body, including, but not limited to, the neck, under the arms (axillae), at the elbows, and in the chest, abdomen, and groin. Lymphocytes are stored within lymph nodes and may also be found in other lymphatic tissues. In addition to the lymph nodes, the lymphatic system includes the spleen, which filters worn-out red blood cells and produces lymphocytes, and bone marrow, which is the spongy tissue inside the cavities of bones that manufactures blood cells. Lymphatic tissue or circulating lymphocytes may also be located in other regions of the body. There are two main types of lymphocytes: B-lymphocytes (B-cells), which may produce specific antibodies to neutralize certain invading microorganisms, and T-lymphocytes (T-cells), which may directly destroy microorganisms or cancer cells, or assist in the activities of other lymphocytes.

The specific symptoms and physical findings of follicular lymphoma can vary from one person to another, depending upon the extent and region(s) of involvement and other factors. Follicular lymphoma is described as having a relapsing and remitting course; the cancer alternates between flaring up or worsening for a period of time often requiring treatment, and periods of time where the cancer is in remission or levels off. For many people, follicular lymphoma is a slow-growing cancer that develops over many years.

The exact, underlying cause of follicular lymphoma is not fully understood. The reason why cancer develops is a complex question and researchers speculate that multiple factors are involved in the development of follicular lymphoma. These factors include genetic, environmental and immunologic factors, which all may play a role in the development of this cancer. About 85% of affected adults have a genetic abnormality that is not inherited, but found only within the cancer cells called a translocation.

Follicular lymphoma affects both men and women, but is slightly more common in women. This form of cancer is found all over the world and can affect people of all races. It is less common in individuals of Asian or African heritage than it is in other ethnicities. The mean age at diagnosis is 65. In the United States and Western Europe, follicular lymphoma is the second most common subtype of non-Hodgkin lymphoma accounting for about 30%-35% of people with non-Hodgkin lymphoma and almost 75% of people with indolent forms of lymphoma. Each year, 15-20,000 people in the U.S. are diagnosed with follicular lymphoma. Pediatric follicular lymphoma is extremely rare variant that makes up only 1-2% of all malignant lymphomas in children. Non-Hodgkin lymphoma, as a group, accounts for about 4.3% of people with cancer in the United States.

Symptoms of the following disorders can be similar to those of follicular lymphoma. Comparisons may be useful for a differential diagnosis.

A diagnosis of follicular lymphoma is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Such testing is necessary to confirm the specific type (and subtype) of non-Hodgkin lymphoma, to determine the nature and extent of the cancer, and to determine the most appropriate treatments.


Fountain syndrome

intellectual disability-deafness-skeletal abnormalities-coarse face with full lips

Fountain syndrome is an extremely rare genetic multisystem disorder that is characterized by intellectual disability; abnormal swelling of the cheeks and lips due to the excessive accumulation of body fluids under the skin (subcutaneous) of the face (edema); skeletal abnormalities; and/or deafness due to malformation of a structure (cochlea) within the inner ear. The exact underlying cause of Fountain syndrome is unknown. The disorder is believed to be inherited as an autosomal recessive trait.

Although researchers have been able to establish a syndrome with characteristic or core symptoms, much about the disorder is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorder prevent physicians from developing a complete picture of associated symptoms and prognosis.

The exact underlying cause Fountain syndrome is unknown. The disorder is believed to be inherited in an autosomal recessive manner. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Fountain syndrome is an extremely rare inherited disorder that is believed to affect males and females in equal numbers. Only several cases have been reported in the medical literature. The exact incidence or prevalence of the disorder is unknown. Because cases may go undiagnosed or misdiagnosed, determining the true frequency of Fountain syndrome in the general population is difficult.

Symptoms of the following disorders can be similar to those of Fountain syndrome. Comparisons may be useful for a differential diagnosis:

Fountain syndrome is usually diagnosed during infancy or early childhood, based upon a thorough clinical evaluation, characteristic physical findings, and a variety of specialized tests.