May Hegglin Anomaly

Dohle Leukocyte Inclusions with Giant Platelets

May-Hegglin Anomaly is a rare, inherited, blood platelet disorder characterized by abnormally large and misshapen platelets (giant platelets) and defects of the white blood cells known as leukocytes. The defect of the white blood cells consists of the presence of very small (2-5 micrometers) rods, known as Dohle bodies, in the fluid portion of the cell (cytoplasm). Some people with this disorder may have no symptoms while others may have various bleeding abnormalities. In mild cases, treatment for May-Hegglin Anomaly is not usually necessary. In more severe cases, transfusions of blood platelets may be necessary.

Some people with May-Hegglin Anomaly may have symptoms at birth while others may have no symptoms throughout their lifetime.  Symptoms may include red or purple colored spots on the skin (purpura), nose bleeds (epitaxis), excessive bleeding from the mouth during dental work, headaches, and/or muscle weakness on one side of the body due to bleeding within the brain (intracranial bleeding).

May-Hegglin Anomaly is inherited as an autosomal dominant genetic trait. The gene involved has been mapped to Gene Map Locus 22q11.2, and the protein generated by the gene is known as MYH9.

May-Hegglin Anomaly is a rare blood platelet disorder that affects males and females in equal numbers.  It occurs more often in people of Greek or Italian descent than among others.  As of about 10 years ago, only about 170 cases were reported in the literature.

Symptoms of the following disorders can be similar to those of May-Hegglin Anomaly.  Comparisons may be useful for a differential diagnosis:

Hemophilia is a rare inherited blood clotting (coagulation) disorder caused by inactive or deficient blood proteins (usually factor VIII).  Factor VIII is one of several proteins that enables the blood to clot.  Hemophilia is found in males almost exclusively and can be classified as mild, moderate, or severe.  The most serious symptom of Hemophilia is uncontrolled internal bleeding that may begin spontaneously without any apparent cause.  Internal bleeding may cause permanent damage to the joints and muscles.  People with Hemophilia bleed for a longer period of time than people who have the normal percentage of active clotting factors in their blood.  Bruises and trauma can trigger episodes of serious internal bleeding in males with this disorder. (For more information on this disorder, choose Hemophilia as your search term in the Rare Disease Database.)

The diagnosis of May-Hegglin Anomaly is made by specialized blood tests that reveal giant, oddly shaped platelets and characteristic cellular inclusions in certain white blood cells (leukocytes). There also might be fewer platelets than normal (mild thrombocytopenia). In severe rare cases, people with May-Hegglin Anomaly may require transfusions of platelets. People with Chediak-Higashi Syndrome, a form of Albinism, have cellular inclusions that are very similar to those of May-Hegglin Anomaly.


Mayer-Rokitansky-Küster-Hauser syndrome

congenital absence of the uterus and vagina (CAUV)

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare disorder that affects women. It is characterized by the failure of the uterus and the vagina to develop properly in women who have normal ovarian function and normal external genitalia. Women with this disorder develop normal secondary sexual characteristics during puberty (e.g., breast development and pubic hair), but do not have a menstrual cycle (primary amenorrhea). Often, the failure to begin the menstrual cycle is the initial clinical sign of MRKH syndrome. The range and severity of MRKH syndrome can vary greatly and the disorder is generally broken down into type I, which occurs as an isolated finding, and type II, which occurs with abnormalities of additional organ systems including mainly the kidneys and the skeleton. Because of the nature of the disorder, MRKH syndrome can cause significant psychological challenges and counseling is recommended. The exact cause of MRKH syndrome remains largely unknown, but there is now no doubt of a genetic origin. In this respect, an update on the most recent research publications shows the involvement of several chromosomal segments, some of them including genes likely to account for the disorder.

The symptoms of MRKH syndrome vary greatly from one woman to another. It is important to note 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.

The exact cause of MRKH syndrome remains largely unknown but ongoing research has begun to provide some clues to its mechanism. Initially, MRKH syndrome was thought to occur randomly (sporadically) due to the involvement of non-genetic or environmental factors such as gestational diabetes or exposure to a teratogen, which is an agent that can disrupt the development of an embryo. No link between an environmental cause and MRKH syndrome has ever been established.

MRKH syndrome is estimated to affect 1 in 4,000-5,000 women in the general population. It is the second most common cause of primary amenorrhea. The disorder is thought to be underdiagnosed making it difficult to determine the true frequency of MRKH syndrome in the general population. The disorder is present at birth (congenital) but is often not identified until early adolescence.

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

In most cases, females with MRKH syndrome come to the attention of physicians due to the failure of menstrual cycles to begin during puberty (primary amenorrhea). Some may seek medical attention due to fertility problems. In rare cases, multiple congenital malformations and/or symptoms caused by renal abnormalities may lead to a possible diagnosis of MRKH syndrome type II.


McCune-Albright syndrome

The range of severity of McCune-Albright syndrome is broad: some children are diagnosed in early infancy with obvious anomalies of bone and increased hormone production by one or more of the endocrine glands; others show no evidence of bone, skin or endocrine malfunction in childhood and may enter puberty at an appropriate age. The degree of severity of individual symptoms may also vary greatly. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below and that every individual case is unique. Parents should talk to their child’s physician and medical team about their specific case, associated symptoms and overall prognosis.

McCune-Albright syndrome is caused by a 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 MAS 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).

McCune-Albright syndrome affects males and females in equal numbers. Precocious puberty is more common in females. The disorder is estimated to affect 1 in 100,000 to 1 in 1,000,000 individuals in the general population. Because the disorder is difficult to diagnose, affected individuals may go undiagnosed or misdiagnosed, making it difficult to determine the true frequency of MAS in the general population.

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

The diagnosis of McCune-Albright syndrome may be suspected at birth based upon identification of the characteristic skin pigmentations (cafe-au-lait spots). However, in many cases, the disorder may not be suspected until late infancy or childhood when precocious puberty develops or when bone deformities become obvious. A diagnosis may be confirmed based upon characteristic physical findings (i.e., association of characteristic skin, bone, and endocrine abnormalities), a detailed patient history, thorough clinical evaluation, and specialized tests including x-ray studies and blood tests.


Cartilage-hair hypoplasia

McKusick Type Metaphyseal Chondrodysplasia

Unevenly short arms and legs (short limbed dwarfism) are the most common features in McKusick type metaphyseal chondrodysplasia and are seen in almost all affected individuals. Increased inward curvature of the lower spine (lumbar lordosis) and increased side curvature of the rest of the spine (scoliosis) also cause a shorter height in affected individuals. Median height is estimated to be around 4 feet 3 inches in males and 4 feet 0 inches in females. In individuals with the more severe form, anauxetic dysplasia (AD), the median height is less than 2 feet 10 inches.

McKusick type metaphyseal chondrodysplasia is caused by changes (variants) in the RMRP gene. More than 90 different disease-causing variants (pathogenic variants) have been reported.

McKusick type metaphyseal chondrodysplasia affects both males and females in equal proportions. The disease has been reported in about 700 individuals. The most severe form, anauxetic dysplasia (AD) is rare, and has been reported in less than 10 individuals.

Symptoms of the following disorders may be similar to those of McKusick type metaphyseal chondrodysplasia. Comparisons may be useful for a differential diagnosis:

Shwachman-Diamond syndrome (SDS) is an extremely rare inherited condition that affects around 1: 77,000 newborns. Shwachman Diamond syndrome is characterized by decreased intestinal absorption of nutrients (intestinal malabsorption) and abnormal function of the pancreas (pancreatic insufficiency). The bones of individuals with SDS do not develop normally, especially in their ribs, arms and leg bones (metaphyseal dysostosis). This can lead to shortened height. Individuals with SDS also have thickening of their ribs and connective tissue (costochondral thickening), causing the ribs to be abnormally short. Additionally, decreased bone marrow production leads to decreased blood cell production (pancytopenia) in most affected individuals. Shwachman-Diamond syndrome is inherited in an autosomal recessive pattern and is caused by variants in the SBDS gene. (For more information on this disorder, choose Shwachman as your search term in the Rare Disease Database).


Allan-Herndon-Dudley syndrome

MCT8-Specific Thyroid Hormone Cell Transporter Deficiency

MCT8-specific thyroid hormone cell transporter deficiency (MCT8 deficiency) is a genetic disorder characterized by severe intellectual disability, an impaired ability to speak, low muscle tone (hypotonia), disorganized movements and specific thyroid test abnormalities.

MCT8 deficiency is primarily characterized by severe intellectual disability, hypotonia and movement abnormalities. As mentioned above, an affected infant typically appears to develop normally (except for hypotonia) until about 2 months of age, when they may seem to have generalized weakness and be unable to hold up their head. Family members have described this feature as limber neck. Due to low muscle tone, weakness, severely reduced motor development and/or other factors, affected children are unable to walk or walk with great difficulty.

MCT8 deficiency is caused by a change (pathogenic variant or mutation) in the MCT8 (SLC16A2) gene leading to an altered structure and function of the MCT8 protein. So far, 210 distinct MCT8 gene variants have been identified in patients with MCT8 deficiency. The severity of clinical symptoms can vary depending on the type of gene variant.

MCT8 deficiency is a rare inherited disorder that affects mostly males. More than 300 families have been identified with 210 different MCT8 gene variants. The frequency of MCT8 deficiency among people with intellectual disability is not known, though estimated to occur in 1 in 70,000 newborns.

Symptoms of the following disorders may be similar to those of MCT8 deficiency. Comparisons may be useful for a differential diagnosis:

Angelman syndrome (AS) is a rare genetic neurological disorder characterized by severe developmental delays and learning disabilities; the absence or near absence of speech; an inability to coordinate voluntary movements (ataxia) and tremulous, jerky movements of the arms and legs and a distinct behavioral pattern characterized by a happy disposition and unprovoked episodes of laughter and smiling, often at inappropriate times. Additional symptoms may occur in some patients including seizures, sleep disorders and feeding difficulties. Some affected children may have distinctive facial features. AS is caused by deletion of or abnormal expression of the UBE3A gene. Most cases of AS appear to occur spontaneously. (For more information on this disorder, choose Angelman as your search term in the Rare Disease Database.)


MDR3 Deficiency

进行性家族性肝内胆汁淤积3型

The age of onset, severity and specific symptoms of MDR3 deficiency can vary greatly from one person to another. In PFIC3, cholestasis may be present in newborns babies (neonatal period). Individuals with mild forms of this disorder may not develop symptoms until young adulthood or middle age where MDR3 deficiency may manifest as mild abnormalities in liver blood tests, gallstones, jaundice and/or itching during pregnancy, or as scarring of the liver and/or yellowing of the eyes and skin.

MDR3 deficiency occurs due to changes called disease-causing variants in the ABCB4 gene.

MDR3 deficiency affects males and females in equal numbers. The exact incidence and prevalence of MDR3 deficiency is unknown. Fewer than 500 cases of PFIC3 have been reported in the medical literature. Because milder forms of MDR3 deficiency often go unrecognized or misdiagnosed, it is difficult to determine the disorder’s true frequency in the general population.

Symptoms of the following disorders can be similar to those of MDR3 deficiency. Comparisons may be useful for a differential diagnosis.

A diagnosis of MDR3 deficiency should be suspected in infants and children with evidence of cholestasis and/or chronic liver disease when the gamma-GGT levels in the blood are elevated. A diagnosis may be made based upon a thorough clinical evaluation, a detailed patient history and a variety of tests.


Meckel syndrome

The specific symptoms associated with Meckel syndrome vary greatly from one individual to another. Affected children will not have all of the symptoms detailed below. Central nervous system, pulmonary or kidney abnormalities always result in perinatal death.

Meckel syndrome can be caused by changes (mutations) in thirteen genes: B9D1, B9D2, CC2D2A, CEP290, MKS1, RPGRIP1L, TCTN2, TCTN3, TMEM67, TMEM107, TMEM216, TMEM231 and TMEM237. Mutations in these 13 genes account for 75 percent of all cases; the remaining 25 percent have unknown genetic causes. Most of these genes are also responsible for a neurological disorder called Joubert syndrome, leading to the concept that Meckel syndrome is the extreme lethal form of Joubert syndrome.

Meckel syndrome affects males and females in equal numbers. More than 200 cases have been reported in the medical literature. The incidence of Meckel syndrome is estimated in various areas around the world to be 1 in 13,250 to 1 in 140,000 live births. The disorder is more common in the Finnish population due to a founder effect, with an incidence of 1 in 9000 and 1 in 3,000 people of Belgian ancestry. However, Gujarati Indians have a prevalence of 1 in 1,300. It occurs more frequently in the context of consanguineous unions.

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

Smith-Lemli-Opitz (SLO) syndrome is a rare hereditary developmental disorder characterized multiple abnormalities that are present at birth (congenital). Symptoms may include characteristic facial features, microcephaly, growth restriction, intellectual disability, extra fingers or toes (polydactyly), loss of vision, incomplete development of the male genitalia, short nose with displaced nostrils and a smaller than normal size opening of the stomach (pyloric stenosis). In some patients, brain or heart abnormalities may be present. The specific symptoms associated with each person vary greatly. Smith-Lemli-Optiz syndrome is inherited in an autosomal recessive pattern. (For more information on this disorder, choose Smith-Lemli-Opitz as your search term in the Rare Disease Database.)


Proximal Xq28 duplication syndrome

MECP2 duplication syndrome is characterized by a wide variety of symptoms. 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 patients, the lack of large clinical studies, and the possibility of other genes influencing the disorder hamper 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.

MECP2 duplication syndrome is caused by a genetic abnormality in which a portion of the X chromosome appears two times on one of the X chromosomes (duplication) instead of once. By definition, the affected region always contains the methyl-CpG-binding protein 2 (MECP2) gene. Most affected children have very small duplications called microduplications, but larger, more complex rearrangements (e.g. translocations) can also cause the disorder. Depending upon the exact size and location of the duplicated area, additional genes are also duplicated. The duplication size is unique to each affected family or individual.

The exact incidence and prevalence of MECP2 duplication syndrome in the general population is unknown. Because affected individuals may go undiagnosed or misdiagnosed, determining the disorder’s true frequency in the general population is difficult. Well over 200 individuals have been reported in the medical literature. It has been estimated that approximately 1-2% of unexplained cases of X-linked intellectual disability may be due to MECP2 duplication syndrome.

Symptoms of the following disorders can be similar to those of MECP2 duplication syndrome. Comparisons may be useful for a differential diagnosis.

A diagnosis of MECP2 duplication syndrome is based upon the identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. It should be included in the differential diagnosis of male infants with hypotonia.


Celiac artery compression syndrome

The median arcuate ligament syndrome (MALS) is a cause of chronic abdominal pain affecting both children and adults alike. Chronic abdominal pain is a very common condition that can have significant negative, long-term psychosocial consequences, including increased risk for anxiety, school and work absences, poor functional capacity, and a poor quality of life. While the exact cause of the pain is unknown, compression of the celiac artery and/or the celiac plexus nerves by the diaphragm can result in pain that is worsened with eating or sometimes with exercise. Other symptoms include nausea and weight loss. In some patients the symptoms can be devastating and can lead to erroneous diagnoses of an eating disorder, psychiatric conditions, or functional abdominal pain (e.g. irritable bowel syndrome, abdominal migraine). The diagnosis is made based on a combination of the clinical symptoms and radiology imaging. There is a surgical procedure that can be performed that is effective in approximately 60-80% of patients.

Compression of the celiac artery by the median arcuate ligament is a poorly understood vascular compression syndrome involving the celiac artery and celiac nerve plexus that results in upper abdominal pain (frequently made worse with eating), weight loss, nausea and vomiting. Sometimes a doctor may hear a soft whooshing sound with a stethoscope (bruit) over the upper abdomen that may mean there is a vascular blockage. Some patients who are athletes may experience recurrent upper abdominal pain that is brought on by moderate to intense cardiovascular work outs. Additional symptoms associated with the diagnosis, but frequently indicative of other medical problems include palpitations (hearing or feeling your own heartbeat), chest pain, diarrhea, constipation, and difficulty sleeping.

The median arcuate ligament is formed by the merging of the right and left attachments of the diaphragm as they cross over the aorta as it enters the abdominal cavity from the chest. The relationship of the ligament to the celiac artery origin determines compression: when the celiac artery comes off the aorta above the diaphragm, this can result in compression; when the celiac artery branches off the aorta below the diaphragm, there is no compression. In a study of 75 autopsies, the median arcuate ligament crossed the celiac artery origin entirely (33%) or partially (48%) in a majority of individuals, resulting in significant celiac artery compression.1

The characteristic MALS patient is more likely to be young adult female, which is consistent with demographic characteristics of other chronic abdominal pain (CAP) patients. However, given the wide distribution of celiac artery compression, the syndrome affects both young and old as well as women and men.

The signs and symptoms of MALS are vague and overlap with a number of common and uncommon medical diagnoses (table 1).

Because there are many patients with celiac artery compression and no symptoms, and because there are many causes for abdominal pain, it is important that patients are evaluated for all possible common causes of abdominal pain before being diagnosed with MALS. (Table 1)


中链酰基辅酶A脱氢酶缺乏

Medium chain acyl-CoA dehydrogenase deficiency

Medium Chain Acyl CoA Dehydrogenase Deficiency

Symptoms of MCADD are metabolic crisis brought about by low blood sugar (hypoglycemia). Because infants are typically weaned from nighttime feedings sometime between 3 and 24 months of age, this is when an infant’s first experience with longer fasting occurs. A previously healthy child with MCADD might suddenly experience severe symptoms at this point. A child could also have symptoms in response to a mild disease like a cold since this can decrease appetite. Alternatively, an individual with a milder form of MCADD might first develop symptoms in adulthood in response to an extreme metabolic stress such as surgery or severe illness. A person with MCADD who never experiences low blood sugar would never develop symptoms of the disease.

MCADD is a genetic disorder of mitochondrial fatty acid beta-oxidation. This means that fats in the body cannot efficiently be broken down and used for energy. The body relies on glucose (a sugar) for energy, and during times when the amount of glucose in the blood is too low, the body can break down fat stores and convert them to glucose. Enzymes called acyl-coenzyme A dehydrogenases are necessary for one of the steps in the biochemical pathway by which fat is broken down into glucose. Medium chain acyl-coenzyme A dehydrogenase (MCAD) is one of these enzymes.

In the general population, MCADD occurs in approximately 1 in 50,000 individuals. The prevalence of MCADD in people of northern European descent has been estimated to be in the range of 1 in 6,400 to 1 in 46,000 individuals. Gypsies of Portugal and Native Americans of California also have a higher-than-average prevalence.

There are no other known disorders caused by variants in the ACADM gene. However, MCADD is in a family of many enzymes that are important in the breakdown of fat for energy. For example, short-, long-, and very long- chain acyl-CoA dehydrogenases. It is possible for any one of these enzymes to be dysfunctional due to gene variants and this could lead to a disorder similar to MCADD. These conditions are known as fatty acid oxidation disorders. Many fatty acid oxidation disorders have symptoms that are similar to MCADD, but they usually also have specific symptoms that help to distinguish them. For example, the additional symptoms of heart problems or lung issues would be more indicative of a deficiency in another type of enzyme, rather than MCADD. (For more information on such alternate disorders, choose Acyl CoA Dehydrogenase as your search term in the Rare Disease Database.)

MCADD is usually diagnosed after newborn screening by a blood test. The test measures the amount of chemicals known as acylcarnitines. High levels of a type of acylcarnitine called octanoylcarnitine are characteristic of MCADD, but this is not specific to this disorder. Follow-up testing is needed to confirm the diagnosis. If an infant develops the classic symptoms of MCADD or dies after being otherwise healthy, a diagnosis of MCADD should be considered. This means that vomiting, lethargy and seizures after a period of fasting or a common illness in a previously healthy person would suggest MCADD. Additionally, low blood sugar (hypoketonic hypoglycemia) in response to fasting or illness would be a more measurable sign of the disorder. Genetic testing to identify two disease-causing variants in the ACADM gene can confirm the diagnosis. Genetic counseling is recommended for affected individuals.


Medullary sponge kidney

Medullary Sponge Kidney is a rare disorder characterized by the formation of cystic malformations in the collecting ducts and the tubular structures within the kidneys (tubules) that collect urine. One or both kidneys may be affected. The initial symptoms of this disorder may include blood in the urine (hematuria), calcium stone formation in the kidneys (nephrolithiasis) or infection. The exact cause of Medullary Sponge Kidney is not known.

The first symptoms of Medullary Sponge Kidney typically blood in the urine, stone formation or signs of a urinary infection such as excessive urination (polyuria) and/or burning and pain while urinating.  In some affected individuals, calcium stones may form in the kidneys (nephrolithiasis).  These stones can cause low back pain in the area of the kidneys (renal colic) and pain in the lower back and lower abdomen.  A prominent feature of Medullary Sponge Kidney is the excretion of small stones with the urinary flow.  The passage of these stones can be profoundly painful.  In a small number of cases, repeated urinary infections and damage to the kidneys may occur if stones become sufficiently large enough to block the flow of urine to the bladder (renal obstruction).

The exact cause of Medullary Sponge Kidney is not known and most cases occur sporadically for no apparent reason.  Some cases are thought to run in families (familial) and may be inherited as an autosomal dominant genetic trait.  However, this inheritance pattern has not been proven.  Some studies have suggested there may be a a possible relationship between overactivity of the parathyroid gland (Hyperparathyroidism) and Medullary Sponge Kidney.

Medullary Sponge Kidney is a rare disorder that affects slightly more women than men.  It is thought to occur in 1 in 1,000 to 5,000 people in the United States.  Although the symptoms of Medullary Sponge Kidney may begin at any age, they usually develop during adolescence or in adults between the ages of 30 and 50 years.  Approximately 13 percent of all people who develop kidney stones are eventually diagnosed with Medullary Sponge Kidney. Medullary Sponge Kidney may also develop in people with Beckwith-Wiedemann Syndrome.  (For more information on Beckwith-Wiedemann Syndrome, see the related disorders section of this report.)

Related Disorders Symptoms of the following disorders can be similar to those of Medullary Sponge Kidney.  Comparisons may be useful for a differential diagnosis:

Medullary Sponge Kidney is associated with several developmental and genetic disorders including the following conditions.  Comparisons may be useful for a differential diagnosis.

The diagnosis of Medullary Sponge Kidney Disease may be confirmed by a thorough clinical evaluation and specialized X-ray studies (i.e., intravenous urography) that reveal the presence of abnormal widening (dilatation) or stretching of collecting ducts, cyst formations or kidney stones. CT scan (computerized tomography) is another imaging study that is effective in revealing calcifications that may later form kidney stones. In some affected individuals, urinary filtration rates (glomerular) may be measured and found to be reduced.


Medulloblastoma

primitive neuroectodermal tumor of the posterior fossa

Medulloblastoma is the most common malignant brain tumor in children. Medulloblastomas by definition occur in the cerebellum, which is the part of brain located at the base of the skull, just above the brainstem. The cerebellum is involved in many functions including coordination of voluntary movements (e.g., walking, fine motor skills) and regulating balance and posture. Medulloblastomas arise from primitive, undeveloped cells in the brain. Most medulloblastomas occur in infants and children. Less commonly, these tumors can develop in adults as well. Symptoms associated with a medulloblastoma include headaches in the morning that improve as the day goes on, recurrent vomiting and difficulty walking and with balance. Medulloblastomas can spread to other areas of the central nervous system. The exact cause of a medulloblastoma is unknown.

The specific symptoms associated with a medulloblastoma will vary from one person to another based upon the exact location and size of a medulloblastoma and whether the tumor has spread to other areas. 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.

The exact underlying cause of medulloblastoma is unknown. Most cases occur randomly for no apparent reason (sporadically).

Medulloblastomas can affect individuals of any age, but occur most often in children under the age of 15 with a peak incidence between 3 and 9 years of age. Medulloblastomas are the most common malignant brain tumor in children. Approximately 80 percent of affected individuals are under the age of 15. Medulloblastomas are extremely rare in adults accounting for 1-2 percent of all cases of brain tumors in adults. In adults, most medulloblastomas occur in individuals between 20-44 years of age. Medulloblastomas are extremely rare in individuals over the age of 45.

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

Medulloblastoma is diagnosed based upon thorough clinical and neurological evaluation, detection of characteristic symptoms and physical findings, patient history, and specialized diagnostic tests. Such studies may include blood tests; evaluation of visual acuity, visual fields, and eye movements; the use of an instrument (ophthalmoscope) that visualizes the inside of the eyes (i.e., to detect papilledema); advanced imaging techniques; and/or other diagnostic tests.


5q14.3 microdeletion syndrome

5q14.3微缺失综合征

Typically, there are no distinctive signs during pregnancy or delivery of a child with MEF2C deficiency. The individual seems to develop normally in the neonatal period and it is not until infancy or early childhood when symptoms such as hypotonia, feeding difficulties and poor eye contact appear. Seizures may occur, especially when the baby has an illness or fever. Global developmental delay is found in nearly all MEF2C deficiency patients. There is variety in these developmental delays, specifically with speech, gait, cognitive abilities and social skills. These patients also present with some mild to severe distinctive facial features.

MEF2C deficiency is caused by mutations in the MEF2C gene or in the gene’s promoter and enhancer regions, resulting in a lack or total absence of functional MEF2C protein. In most cases, MEF2C deficiency is de novo, meaning it is caused by spontaneous changes in DNA sequence and not inherited from a patient’s parents. The MEF2C gene codes for a transcription factor that is involved in normal development of the heart, brain, craniofacial, vascular (blood flow), and immune systems of the body. The MEF2C enhancer region is widely expressed in glial cells, which are cells that support brain and nervous system cells.

MEF2C deficiency appears to equally affect males and females, and it does not seem to have an ethnic predisposition. The age of onset is most commonly in infancy or early childhood. MEF2C deficiency is often misdiagnosed as Rett syndrome due to its Rett-like phenotype. There have been around 50 patients identified with MEF2C deficiency, but this number should likely be larger due to misdiagnosis of subtle symptoms that present similarly to other more well-known disorders.

MEF2C deficiency has clinical overlap with Rett Syndrome, Angelman Syndrome, Pitt-Hopkins syndrome, and CDKL5 deficiency disorder. Often, these syndromes are grouped under the term Rett-like, but using this term has recently been discouraged because these syndromes are now recognized as clinically different from each other. Symptoms of the following disorders can be similar to those of MEF2C deficiency. Comparisons may be useful for a differential diagnosis.

Hypotonia and epilepsy are symptoms that may lead to a suspicion of MEF2C deficiency.


Megalencephaly-Capillary Malformation

巨脑-毛细血管畸形-多小脑回综合征

The symptoms and severity of MCAP vary greatly from one person to another. Some individuals may develop milder symptoms, while others have more serious complications and it is important to note that affected individuals may not have all of the symptoms discussed below. Families of affected children should talk to their physician and medical team about their specific features, associated symptoms and discuss their medical management and overall prognosis.

Most cases of MCAP are caused by variants in the PIK3CA gene. Most of the identified variants are not inherited, but occur in a fraction of cells as the baby develops (I.e., post-zygotic mutations). While there are reports of family members with large heads (or megalencephaly), recurrence in family members (e.g., siblings or parents) with MCAP have been reported in the medical literature. Advanced paternal age has been noted in some patients but this association is not proven.

The exact incidence of macrocephaly-capillary malformation is unknown. Since its first description as a distinct entity in 1997, more than 200 affected individuals have been reported. Some patients may go unrecognized or misdiagnosed making it difficult to determine the true frequency of MCAP in the general population. Males and females appear to be affected in equal numbers.

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

A diagnosis of macrocephaly-capillary malformation may be confirmed through a thorough clinical evaluation that includes a detailed history and physical examination looking for MCAP-associated features. Molecular diagnosis requires demonstration of a mosaic activating mutation in PIK3CA, which may require advanced genetic testing to be performed on affected tissues (e.g., skin fibroblasts) or samples other than blood. Different diagnostic criteria have been proposed in the medial literature.

Treatment and surveillance of a child affected with MCAP may require the coordinated efforts of a team of specialists including a pediatrician, neurologist, developmental specialists, orthopedic surgeon, ophthalmologist, and, in some cases, neurosurgeon, dermatologist and other healthcare professionals who may need to systematically and comprehensively plan an affected child’s treatment.


二氢叶酸还原酶缺乏所致巨幼细胞性贫血

Constitutional megaloblastic anemia with severe neurologic disease

constitutional megaloblastic anemia with severe neurological disease

Megaloblastic anemia is characterized by unusually large, structurally abnormal blood cells (megaloblasts) that do not function normally. Bone marrow, the soft spongy material found inside certain bones, produces the main blood cells of the body – red blood cells, white blood cells and platelets. All three cell lines may be affected in megaloblastic anemia. Anemia is a condition characterized by low levels of circulating red blood cells. Red blood cells are released from the marrow into the bloodstream where they travel throughout the body delivering oxygen to tissue. A deficiency in healthy, fully-matured red blood cells can result in fatigue, paleness of the skin (pallor), lightheadedness and additional findings. Megaloblastic anemia has several different causes – deficiencies of either cobalamin (vitamin B12) or folate (vitamin B9) are the two most common causes; dihydrofolate reductase deficiency is another more uncommon cause. Vitamin B12 and vitamin B9 play an essential role in the production of red blood cells. This disease can be diagnosed based on laboratory tests or characteristic findings when tissue is viewed under microscope.

In most patients, megaloblastic anemia develops slowly, and affected individuals may not have any apparent symptoms (asymptomatic) for many years. Symptoms common to anemia usually develop at some point and may include fatigue, paleness of the skin (pallor), shortness of breath, lightheadedness, dizziness and a fast or irregular heartbeat. The specific symptoms present in each individual can vary greatly.

The most common causes of megaloblastic anemia are deficiency of either cobalamin (vitamin B12) or folate (vitamin B9). These two vitamins serve as building blocks and are essential for the production of healthy cells such as the precursors to red blood cells. Without these essential vitamins, the creation (synthesis) of deoxyribonucleic acid (DNA), the genetic material found in all cells, is hampered.

Megaloblastic anemia affects males and females in equal numbers. It can occur in individuals of any racial or ethnic background. Because the causes of megaloblastic anemia vary and because some individuals may not exhibit any obvious symptoms, determining its true frequency in the general population is difficult. It is estimated that there are less than 1,000 people in the U.S. with the disease.

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

A diagnosis of megaloblastic anemia is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings and a variety of blood tests. Blood tests may reveal the abnormally large, misshapen red blood cells that characterize megaloblastic anemia. Blood tests can also confirm cobalamin or folate deficiency as the cause of megaloblastic anemia. Additional tests such as a Schilling test, which confirms poor absorption as the cause of cobalamin deficiency, may be necessary.


球形角膜-智力障碍综合征

Megalocornea Intellectual Disability Syndrome

Megalocornea-intellectual disability syndrome is an extremely rare disorder that is characterized by distinctive abnormalities of the cornea of the eye (megalocornea) and varying degrees of cognitive impairment (intellectual disability). Most patients also present with diminished muscle tone (hypotonia) and may experience a wide variety of additional symptoms that can vary in severity. Individuals are typically diagnosed during early infancy or early childhood. To date, there have been approximately 40 individuals reported with megalocornea-intellectual disability syndrome in the medical literature. While the exact cause of this condition is unknown, it is suspected to have a genetic basis.

A characteristic symptom of all individuals affected with megalocornea-intellectual disability syndrome is a distinctive eye abnormality known as megalocornea, which is the abnormal, nonprogressive enlargement of the cornea that occurs without the presence of increased pressure within the eye (glaucoma). The cornea is the clear (transparent) outer layer of the eye and has two functions – it protects the rest of the eye from dust, germs and other harmful or irritating material and it acts as the eye’s outermost lens, bending incoming light onto the inner lens, where the light is then directed to the retina (a membranous layer of light-sensing cells in the back of the eye). The retina converts light to images, which are then transmitted to the brain. The cornea must remain clear to be able to focus incoming light. Megalocornea is present at birth (congenital) and usually affects both eyes (bilateral). Although the cornea is abnormally enlarged, it is otherwise normal in structure, curvature and thickness.

The exact cause of megalocornea-intellectual disability syndrome is unknown. However, cases reported in the literature are consistent with an autosomal recessive inheritance pattern or new (de novo) genetic changes (variants) that were not inherited from parents.

Megalocornea-intellectual disability syndrome is typically diagnosed in early childhood or early infancy. Due to the rarity of the condition and the small number of documented cases, there are no accurate estimates for the incidence of this condition. To date, approximately 40 individuals with the condition have been reported in the medical literature. Most are sporadic, meaning that individuals are typically the only ones affected with the condition in their families. An approximately equal number of males and females have been reported. Additionally, individuals across varied races have been reported with this condition.

Symptoms of the following disorder can be similar to those of megalocornea-intellectual disability syndrome. Comparisons may be useful for a differential diagnosis.

Megalocornea-intellectual disability syndrome is diagnosed during early infancy or early childhood based on a clinical evaluation, identification of characteristic physical findings and/or a variety of specialized tests. Many researchers agree that the presence of megalocornea and intellectual disability should be considered the minimal criteria upon which to base a diagnosis.

Treatment is directed towards the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, physical therapists and specialists who assess and treat eye problems (ophthalmologists), neurological disorders (neurologists), skeletal disorders (orthopedists) and heart problems (cardiologists) may need to systematically and comprehensively plan an affected child’s treatment.


Ear-patella-short stature syndrome

耳-髌骨-身材矮小综合征

The main clinical features of MGS are small ears, kneecap abnormalities and short stature. These features can be seen at birth and are discussed in more detail below.

MGS can be caused by changes (mutations) in eight different genes (ORC1, ORC4, ORC6, CDT1, CDC6, CDC45L, MCM5 and GMNN). Most forms of MGS are inherited in an autosomal recessive inheritance pattern. MGS type 6 (GMNN gene) is inherited in an autosomal dominant pattern.

Since MGS was first described in 1959, only about 67 cases have been reported in the medical literature (Nov 2019). MGS is estimated to affect less than 1-9 individuals per 1,000,000 people. However, researchers believe this condition is under-diagnosed. MGS affects men and women equally.

Symptoms of the following disorders can be similar to those of MGS. Looking at comparisons may be useful to clarify the diagnosis:

MGS is diagnosed based on the clinical signs and symptoms. The presence of small ears, very small or absent kneecaps and short stature are essential for the clinical diagnosis of MGS.


Meige syndrome is a rare neurological movement disorder characterized by involuntary and often forceful contractions of the muscles of the jaw and tongue (oromandibular dystonia) and involuntary muscle spasms and contractions of the muscles around the eyes (blepharospasm). The specific symptoms and their severity vary from case to case.

Meige syndrome is characterized by the combination of blepharospasm and oromandibular dystonia. The severity of these conditions varies from case to case. Meige syndrome most often affects middle-aged individuals.

The cause of Meige syndrome is unknown. Researchers speculate that the cause of Meige syndrome may be multifactorial (e.g., caused by the interaction of certain genetic and environmental factors).

Meige syndrome affects women more often than men. Symptoms typically begin in middle-age between 40-70 years, although cases have been reported in individuals much younger. The disorder was first described in detail in the medical literature in 1910 by French neurologist Henry Meige.

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

No tests exist to diagnose Meige syndrome. A diagnosis is made based upon a thorough clinical evaluation, a detailed patient history and identification of characteristic symptoms.


Melanoma, Malignan

Malignant Melanoma is a common skin cancer that arises from the melanin cells within the upper layer of the skin (epidermis) or from similar cells that may be found in moles (nevi). This type of skin cancer may send down roots into deeper layers of the skin. Some of these microscopic roots may spread (metastasize) causing new tumor growths in vital organs of the body.

In the early stages, most melanomas do not produce any specific symptoms.  Later they may appear as lesions that do not heal or an existing mole that shows changes in size or color.  A physician should be consulted when any lesion, pigmented or not, becomes itchy, burns, softens or hardens, forms a scab, bleeds, becomes surrounded by a reddened or inflamed area, changes color, size, or shape.

The exact cause of Malignant Melanoma is unknown.  Excessive exposure to the sun, particularly before puberty, and living in areas that are closer to the sun (i.e., tropical climates), increases the risk of developing skin cancer.

Malignant Melanoma affects males and females in equal numbers. The incidence of these types of skin cancers is increasing at a relatively fast rate as compared with other forms of cancer.  The risk of melanoma is higher in people of European descent than in other populations.  A darker pigmentation to the skin may be associated with a lower risk of Malignant Melanoma.  It is also associated with a greater risk for those individuals with blue eyes and a fair complexion.

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

Basal Cell Carcinoma is a common skin cancer. It may appear as small, shiny, firm nodules; ulcerated, crusted lesions; or flat, scar-like hardened patches that may bleed.  Without a biopsy, this type of skin cancer is difficult to differentiate from psoriasis or localized dermatitis.

The treatment for malignant melanoma depends on the level, stage, and location of the skin cancer at the time of diagnosis. For stage 1 disease, surgery to remove the affected area involves a wide excision with 5 cm margins around the lesion. In some locations, such as the face, smaller margins must be accepted. In Stage 2 disease, the cancer has progressed to the lymph nodes; additional surgery then involves complete removal of the involved nodes (lymphadenectomy). Regular follow-ups are advisable and typically include an annual chest x-ray.


MELAS Syndrome

线粒体脑肌病伴乳酸血症和卒中样发作

Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, Stroke-Like Episod

MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes) syndrome is a rare disorder that begins in childhood, usually between two and fifteen years of age, and mostly affects the nervous system and muscles. The most common early symptoms are seizures, recurrent headaches, loss of appetite and recurrent vomiting. Stroke-like episodes with temporary muscle weakness on one side of the body (hemiparesis) may also occur and this can lead to altered consciousness, vision and hearing loss, loss of motor skills and intellectual disability. MELAS is caused by mutations in mitochondrial DNA and in one patient, this syndrome has been associated with mutations in a nuclear gene, POLG1.

Symptoms of MELAS syndrome usually begin between the ages of two and fifteen years, but delayed onset cases have also been reported between fifteen and forty years and late onset cases after forty years.  In approximately 75 percent of cases, onset of the disorder is before the age of 20 years.  Symptoms and physical findings associated with MELAS syndrome vary greatly between affected individuals in the same family and between different families.  The distinguishing feature in MELAS syndrome is the recurrence of stroke-like episodes. It is currently thought that the deficiency of a compound called nitric oxide in the small blood vessels of the brain may be responsible for the stroke-like episodes. Short stature and hearing loss may be present and fatigue and difficulty tolerating exercise may be early symptoms.

MELAS is caused by mutations in mitochondrial DNA (mtDNA). Mutations affecting the genes for mtDNA are inherited from the mother. MtDNA that is found in sperm cells is typically lost during fertilization and as a result, all human mtDNA comes from the mother. An affected mother will pass on the mutation to all her children, but only her daughters will pass on the mutation to their children. Mitochondria, which are found by the hundreds or thousands in the cells of the body, particularly in muscle and nerve tissue, carry the blueprints for regulating energy production.

MELAS syndrome is a rare disorder that affects males and females in equal numbers. Although rare, MELAS syndrome is probably the most common type of mitochondrial myopathy caused by mutations in mtDNA. Some researchers believe that mitochondrial myopathies may go unrecognized and underdiagnosed in the general population, making it difficult to determine the true frequency of disorders like MELAS syndrome.

Kearns-Sayre syndrome is a rare neuromuscular disorder characterized by three primary findings: progressive paralysis of certain eye muscles (chronic progressive external ophthalmoplegia); abnormal accumulation of colored (pigmented) material on the nerve-rich membrane lining the eyes (atypical retinitis pigmentosa), leading to chronic inflammation, progressive degeneration, and wearing away of certain eye structures (pigmentary degeneration of the retina); and heart disease  such as heart block. Other findings may include muscle weakness, short stature, hearing loss, and/or the loss of ability to coordinate voluntary movements (ataxia) due to problems affecting part of the brain (cerebellum). In some cases, Kearns-Sayre syndrome may be associated with other disorders and/or conditions. (For more information on this disorder, choose Kearns Sayre as your search term in the Rare Disease Database.)

MELAS is diagnosed based on clinical findings and molecular genetic testing.


Mal de Meleda

Keratosis Palmoplantaris Transgradiens of Siemens

Meleda disease is an extremely rare inherited skin disorder characterized by the slowly progressive development of dry, thick patches of skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis). Affected skin may be unusually red (erythema) and become abnormally thick and scaly (symmetrical cornification). Affected children may also exhibit various abnormalities of the nails; excessive sweating (hyperhidrosis) associated with an unpleasant odor; and/or, in some cases, development of small, firm raised lesions (lichenoid plaques). The range and severity of symptoms may vary from case to case. Meleda disease is inherited as an autosomal recessive trait.

Meleda disease is an extremely rare inherited skin disorder that is usually obvious shortly after birth.  Initially, affected infants may have unusually red skin on the palms of the hands and the soles of the feet (palmoplantar erythema).  The affected skin then becomes abnormally thick, yellowish-brown, and scale-like (hyperkeratosis).  These skin lesions are usually present on both sides of the body (bilateral) on the same respective areas (symmetrical palmoplantar keratosis).  As the child grows older, these patches may spread to involve the entire hand or foot.  Eventually, the wrists, forearms, and knees may also become involved.  In some cases, with advancing age, the skin on the chest and abdomen may also become dry, scaly, and cracked.  Excessively dry skin may cause pain and discomfort.

Meleda disease is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Meleda disease is an extremely rare disorder that affects males and females in equal numbers.  More than 100 cases have been reported in the medical literature.  The prevalence of Meleda disease in the general population is estimated at one case per 100,000 people.  Skin abnormalities associated with this disorder may be present at birth (congenital).  Other symptoms usually become apparent by the second or third year of life.

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

The diagnosis of Meleda disease may be confirmed by a thorough clinical evaluation that includes a detailed patient history and identification of characteristic physical findings. In most cases, skin abnormalities may be apparent at birth (congenital) or during infancy including characteristic skin abnormalities on the palms of the hands and the soles of the feet.


Melkersson-Rosenthal Syndrome

Melkersson-Rosenthal syndrome is defined by recurrent swelling (edema) of various facial features such as the upper lip, lower lip, one or both cheeks, eyelids, or rarely, one side of the scalp. It is also characterized by recurrent muscle weakness or paralysis (palsy) in the face and deep grooves or cracks (fissures) in the tongue. Affected individuals usually present with only one or two symptoms. It is estimated that about 8-18% of all patients present with all three symptoms.

The cause of MRS is still not known. Some cases of MRS have been attributed with various infections by bacterial or viral agents; it is possible that infection with herpesviruses may be a possible cause for MRS. Dietary and other allergens may also be involved in the development of MRS. Some studies have demonstrated the role of hormonal changes triggering the onset of inflammatory episodes. It is also suspected that MRS may be a secondary symptom of another condition such as Crohn’s disease or sarcoidosis. However, no strong associations exist to explain what causes MRS.

MRS affects individuals of all ages. Typically, onset of symptoms begins in young adulthood but can occur well into adulthood. While it is not common, a few patients have been diagnosed during childhood. Most literature suggests that MRS tends to affect more females than males. Due to the rarity of MRS, accurate data regarding the incidence of this condition is difficult to obtain. It is likely an under-diagnosed condition as many people with MRS are misdiagnosed because the clinical symptoms overlap with many other common conditions.

Bell’s palsy is a nonprogressive neurological disorder of one of the facial nerves (7th cranial nerve). This disorder is characterized by the sudden onset of facial paralysis that may be preceded by a slight fever, pain behind the ear on the affected side, a stiff neck, and weakness and/or stiffness on one side of the face. Paralysis results from decreased blood supply (ischemia) and/or compression of the 7th cranial nerve. The exact cause of Bell’s palsy is not known. Viral (e.g., herpes zoster virus) and immune disorders are frequently implicated as a cause for this disorder. There may also be an inherited tendency toward developing Bell’s palsy. (For more information on this disorder, choose Bell as your search term in the Rare Disease Database).

MRS is diagnosed clinically, based on physical findings and medical history. The presence of persistent or recurrent facial swelling and either facial palsy or tongue findings may be sufficient for a clinical diagnosis. A biopsy of the lips may be necessary to confirm the diagnosis and rule out possible infectious causes, recurrent angioedema, Crohn’s disease, sarcoidosis or cancers. The presence of only one of the clinical features is enough for diagnosis when a biopsy of affected tissues is consistent with MRS. Because of the overlapping features of MRS with other common conditions, time to diagnosis may take years.


Melnick-Needles syndrome

MNS is a congenital condition, meaning it is present from birth. However, different members of the same family can have differences in the severity of their symptoms. Due to this variability, individuals may vary in their age at the time of diagnosis.

MNS is an X-linked dominant genetic disorder caused by an abnormality (mutation) in the FLNA gene which contains instructions for creating a protein called filamin A. The FLNA gene has been mapped to chromosome Xq28.

MNS occurs in females much more often than in males. This is because males with MNS often do not survive to term in pregnancy. Approximately 70 total cases have been reported in the medical literature, but it is likely that there are many more individuals with MNS who haven’t been reported in the medical literature or haven’t been diagnosed.

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

Multiple epiphyseal dysplasia (MED) is a hereditary bone disorder that affects females and males in equal numbers. It can either have an autosomal recessive or autosomal dominant pattern of inheritance. Symptoms begin between two and five years of age with the appearance of a waddling gait. Individuals with MED may experience pain because of joint disease (osteoarthritis). Body size tends to be almost normal, except for the hands and feet which are disproportionately small. (For more information on this condition, choose rMED or dMED as your search terms in the Rare Disease Database.)


Melorheostosis

Melorheostosis is a rare and progressive disease characterized by thickening or widening (hyperostosis) of the outer layers of the bone (cortical bone).

Melorheostosis usually affects a single arm or leg (segment of the appendicular skeleton) and rarely affects both sides of the body. This condition is usually restricted to the inside (medial) or outside (lateral) of the bones. The disease can also affect the axial skeleton: pelvis, sternum, ribs and, more rarely, the spine and skull. Symptoms may progressively worsen over time. Signs and symptoms of melorheostosis may include:

Melorheostosis is usually an isolated disorder. However, it has also been observed in some families with osteopoikilosis or Buschke-Ollendorff syndrome due to a change (mutation or pathogenic variant) in the LEMD3 gene.

The estimated incidence of melorheostosis is 1 in 1,000,000. Approximately 400 cases have been reported. Males and Females are affected in equal numbers.

Melorheostosis can be part of the following conditions:

Treatments are currently limited and mostly aimed at reducing symptoms.


Menetrier Disease

Menetrier disease is a rare disorder characterized by massive overgrowth of mucous cells (foveola) in the mucous membrane lining the stomach, resulting in large gastric folds. The most common symptom associated with Menetrier disease is pain in the upper middle region of the stomach (epigastric pain). The cause of Menetrier disease is unknown.

The symptoms of Menetrier disease may vary from case to case. Some individuals may not exhibit any symptoms (asymptomatic). The most common symptom is pain in the upper middle region of the stomach (epigastric pain). Less frequent reported symptoms include nausea, vomiting, and diarrhea. In some cases, weight loss and profound loss of appetite (anorexia) may also occur.

The exact cause of Menetrier disease is unknown. There may be multiple causes. In children, some cases of Menetrier disease may be associated with infection with cytomegalovirus (CMV). The bacterium Helicobacter pylori has been implicated in some adults with Menetrier disease. The exact role, if any that these infections play in the development of Menetrier disease is unknown.

Menetrier disease affects males slightly more often than females. It most often affects adults in their 50s or older. However, a childhood form of the disorder exists. Because of the confusion in the literature regarding the term Menetrier disease, it is difficult to determine its true frequency in the general population.

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

Zollinger-Ellison syndrome (ZES) is a rare, digestive disorder characterized by the development of a tumor (gastrinoma) or tumors that secrete excessive levels of gastrin, a hormone that stimulates production of acid by the stomach. Many affected individuals develop multiple gastrinomas, approximately half to two-thirds of which may be cancerous (malignant). In most cases, the tumors arise within the pancreas and/or the upper region of the small intestine (duodenum). Due to excessive acid production (gastric acid hypersecretion), individuals with ZES may develop peptic ulcers of the stomach, the duodenum, and/or other regions of the digestive tract. Peptic ulcers are sores or raw areas within the digestive tract where the lining has been eroded by stomach acid and digestive juices. Symptoms and findings associated with ZES may include mild to severe abdominal pain; diarrhea; gastroinestinal bleeding; increased amounts of fat in the stools (steatorrhea); and/or other abnormalities. Individuals with Zollinger-Ellison syndrome may have giant gastric folds. (For more information on this disorder, choose Zollinger-Ellison as your search term in the Rare Disease Database.)


Meningioma

Meningioma can occur at any age but tend to occur in older individuals; the median age at diagnosis is 65 years (meaning that half of diagnosed people will be over that age and the other half below). The potential symptoms of meningioma are variable and depend on the location of the tumor and the locations of the brain and spine that are compromised.

As their name indicates, meningioma is derived from the meninges, which are membranes that cover the brain and spinal cords. More specifically, most meningioma originate from a type of cells within the meninges known as arachnoid cap cells, which are involved in the resorption of cerebrospinal fluid.

In the United States, about 40% of primary brain tumors are meningiomas. In 2023, it is estimated that about 42,000 people will be diagnosed with meningioma. However, this is likely an underestimation, as autopsy data shows that up to 2.8% of individuals have a meningioma. Most of these tumors are too small to cause symptoms and will never grow enough to be clinically significant.

Disorders related to meningioma can be divided in two categories: syndromes with several symptoms and features, one of which is an increased risk of meningioma, and diseases that are not meningioma, but where affected individuals can have similar symptoms to individuals with meningioma.

The diagnosis of meningioma is mostly based on a patient history and physical examination, medical imaging, and analysis of the cells composing the tumor. A patient that has signs and symptoms suggestive of a central nervous system lesion such as recent onset of seizures or neurological deficits (for more details, see the Signs & Symptoms section) will usually undergo brain and/or spine medical imaging with a computed tomography (CT) scan or magnetic resonance imaging (MRI). MRI is the imaging modality of choice for initial evaluation of brain tumors. Although the presence of a meningioma can be suspected with medical imaging due to their characteristic location, analysis of the cells of the tumor provides the most definitive diagnosis. Meningioma cells can be obtained by removing a piece of the tumor with a biopsy. However, meningiomas are usually removed surgically without a prior biopsy as this provides therapeutic in addition to diagnostic benefit. Once tumor cells are obtained, they can be analyzed under the microscope by a pathologist, who will confirm the diagnosis. A laboratory technique called immunohistochemistry can be used to stain meningioma cells to facilitate their identification.


Meningitis, Tuberculous

Tuberculous Meningitis (TBM) is a form of meningitis characterized by inflammation of the membranes (meninges) around the brain or spinal cord and caused by a specific bacterium known as Mycobacterium tuberculosis. In TBM, the disorder develops gradually. Treatment with antibiotics and other drugs is usually effective against the infection.

Tuberculous Meningitis involves the central nervous system.  Headaches and behavioral changes may be noticed initially.  Fever, headache, a stiff neck, and vomiting may also occur.  Symptoms among older children and adults may progress from irritability to confusion, drowsiness, and stupor, possibly leading to coma.

Tuberculous Meningitis is a rare complication that occurs in some patients who have or have had tuberculosis (TB), especially miliary tuberculosis.  It can also occur in people who have been exposed to the bacteria that causes TB.  This form of meningitis is caused by a specific bacteria known as Mycobacterium Tuberculosis.  (For more information on tuberculosis, choose tuberculosis as your search term in the Rare Disease Database).

TBM is usually found in children aged one to five years although it may occur at any age.

Symptoms of the following disorders may resemble those of Tuberculous Meningitis.  Comparisons may be useful for a differential diagnosis:

In general, Meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord.  This inflammation may be caused by different types of bacteria, viruses, fungi, malignant tumors, or reactions to certain injections into the spinal canal.  (For more information on other forms of meningitis, choose meningitis as your search term in the Rare Disease Database.)

Meningitis is usually treated with antibiotic drugs used against the bacteria causing the infection. These may include isoniazid, rifampin, streptomycin, and ethambutol. Treatment should last for at least 9 months to one year. Corticosteroid drugs such as prednisone may also be of benefit.


Meningitis

Meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. The disorder can occur in three different forms: adult, infantile, and neonatal. This inflammation may be caused by different types of bacteria, viruses, fungi, or malignant tumors. Chemical reactions to certain injections into the spinal canal can also cause Meningitis. This inflammation can begin suddenly (acute) or develop gradually (subacute). Adult forms of Meningitis are characterized by fever, headache, and a stiff neck, sometimes with aching muscles. Nausea, vomiting and other symptoms may occur. Treatment with antibiotics is usually effective against the infection.

Meningitis in adults and children is often preceded by respiratory illness or a sore throat.  In its acute form, the disorder is characterized by fever, headache, a stiff neck, and vomiting.  Adults may become seriously ill within 24 hours.  In children, the course of the infection may be even shorter. Symptoms among older children and adults may progress from irritability through confusion, drowsiness, and stupor, possibly leading to coma. Dehydration often occurs, and collapse of the blood vessels may lead to shock (Waterhouse-Friderichsen Syndrome), especially when the Meningitis is caused by meningococcus bacteria which spreads to the blood (septicemia).  Paralysis of one side of the body (hemiparesis) is uncommon early in the course of Meningitis, but may occur later as a result of tissue death in the brain (cerebral infarction).  Meningitis may recur even after treatment with antibiotics.

Meningitis can be caused by different bacteria, viruses and organisms such as Neisseria meningitis, Hemophilus influenzae b, Streptococcus (Diplococcus) pneumoniae, Group A Streptococcus, Escherichia coli or other gram-negative organisms (chiefly Pseudomonas), and Staphylococcus aureus.

Aproximately 3,000 cases of Meningitis have been reported in 1997.  Meningitis caused by Hemophilus influenzae occurs most often in children before the age of five to six years.

Symptoms of the following disorders may resemble those of Meningitis. Comparisons may be useful for a differential diagnosis:

Encephalitis is a brain infection.  There are different types of this disorder which are caused by different types of viruses.  Encephalitis may also be caused by hypersensitivity initiated by a virus or other protein that is foreign to the body.  Symptoms may include headache, drowsiness, hyperactivity, and/or general weakness.  This disorder may have some symptoms similar to those of Meningitis such as a stiff neck, altered reflexes, confusion, speech disorders, possible convulsions, paralysis and coma.  (For more information choose Encephalitis as your search term in the Rare Disease Database.)

Meningitis is usually treated with different types of antibiotics used against the specific bacteria causing the infection. These may include ampicillin, chloramphenicol, gentamicin, penicillin, moxalactam, nafcillin, or in tuberculosis cases isoniazid.


Meningococcal Meningitis

Meningococcal meningitis is a form of meningitis caused by a specific bacterium known as Neisseria meningitidis. Meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. This inflammation can begin suddenly (acute) or develop gradually (subacute). Symptoms may include fever, headache, and a stiff neck, sometimes with aching muscles. Nausea, vomiting and other symptoms may also occur. Skin rashes occur in about half of all individuals with meningococcal meningitis.

Meningococcal meningitis is one of the three most common types of bacterial meningitis. The incubation period averages 3-4 days (range 1-10 days), which is the period of communicability. It progresses more rapidly than any other acute form of bacterial meningitis. Meningococcal meningitis involves the central nervous system. In adults and children it is often preceded by respiratory illness or a sore throat. In its acute form, the disorder is characterized by fever, headache, a stiff neck, nausea, vomiting and altered mental state such as confusion or coma. Adults may become seriously ill within hours. In children the course of the infection may be even shorter.

Meningococcal meningitis is caused by a bacterium known as Neisseria meningitidis. There are several types, or serogroups, of Neisseria meningitidis. The most common of these serogroups are A, B, C, D, X, Y, 29E, and W135. Serogroups A, B, C, and Y are responsible for most meningococcal diseases.

Meningococcal meningitis primarily affects infants, children, and young adults. Males are affected slightly more than females, and account for 55% of all cases, with an incidence of 1.2 cases per 100,000 population, compared to 1 case per 100,000 population among females. Meningococcal meningitis can occur as an epidemic in subgroups such as people in the military services or students in dormitories. Vaccines can help control meningitis epidemics caused by serogroups A, B, C, Y, or W135.

Symptoms of the following disorders may resemble those of meningococcal meningitis. Comparisons may be useful for a differential diagnosis:

In general, meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. This inflammation may be caused by different types of bacteria, viruses, fungi, malignant tumors, or reactions to certain injections into the spinal canal. (For more information on other types of Meningitis, choose meningitis as your search term in the Rare Disease Database.)


Menkes disease

Menkes disease is characterized by dry skin and abnormal hair that is often brittle, tangled, sparse, steely or kinky and is often white, ivory, or grey in color. The affected infant may also appear to have a yellow appearance (jaundice) which is caused by excessive bilirubin in the blood (hyperbilirubinemia). Lower than normal body temperature (hypothermia) also may occur in the neonatal period. The normal, asymptomatic phase of the illness typically lasts for two to three months.

Menkes disease is an X-linked genetic disorder caused by mutations in the ATP7A gene. This gene is responsible for production of the ATPase enzyme that regulates copper levels in the body. Individuals with Menkes disease have an abnormally low level of copper in the brain and liver and excess copper in the intestines and kidneys. Without the copper as a key element in their structure and functioning, the activity of the body’s copper-dependent enzymes is diminished. For example, reduced activity of the cuproenzyme tyrosinase causes reduced pigmentation of the hair and skin. Reduced activity of the cuproenzyme lysine oxidase causes failure of connective tissue to form strong, inner blood vessels walls.

Recent studies suggest that the incidence of Menkes disease is about 1 in 35,000 live male births. The majority of diagnosed infants are male; however, MD may still occur in females, related to unusual genetic circumstances.

Wilson disease is a genetic disorder of copper metabolism characterized by excess copper stored in various body tissues, particularly the liver, brain, and corneas of the eyes. The disease is progressive and if left untreated, may cause liver (hepatic) failure, hemolytic crisis, central nervous system dysfunction, and death. Early diagnosis and treatment may prevent serious long-term disability and life-threatening complications. Treatment is aimed at reducing the amount of copper accumulated in the body by chelation therapy and maintaining normal copper levels thereafter. (For more information on this disorder, please choose Wilson as your search term in the Rare Disease Database.)

The diagnosis of MD is suggested by the appearance of brittle, tangled, sparse, steely or kinky hair at several months of age. Blood tests showing low levels of serum copper and ceruloplasmin support the diagnosis. It is important to note that these levels are typically low in otherwise healthy newborns. A new method of diagnosis that can potential identify affected infants before copper deficiency affects the brain involves measurement of plasma catecholamine levels. This may be the basis for Menkes disease newborn screening in the future. Molecular genetic testing for mutations in the ATP7A gene may also prove to be an efficient method of population-based newborn screening.


Cutaneous neuroendocrine carcinoma

Merkel cell carcinoma most commonly affects regions of the skin that are exposed to the sun including the head/neck and arms, but it can also develop on other areas of the body that are not typically sun-exposed.

Several risk factors have been established for MCC. These include being over the age of 50, having fair-skin, experiencing extensive sun exposure (ultraviolet light), or having an immune system that is either weakened or compromised. Individuals with conditions that suppress the immune system are at elevated risk of developing MCC. However, over 90% of people with MCC do not have any known problem with their immune system.

Approximately 60% of MCC tumors arise in men. In the past 15 years, the incidence has tripled in the United States, and it can be lethal for about one-third of the people affected. As of 2020, approximately 3,000 persons per year are diagnosed with this cancer in the United States. The projected incidence is 3,200 cases by the year 2025.The incidence (number of people who develop a disorder over a given period of time such as one year) is approximately 0.7 people per 100,000 people in the general population of the United States. It dramatically increases to approximately 9.8 people per 100,000 in individuals more than 85 years of age. There is a 100,000-fold difference between the risk of developing MCC for patients under the age of 30 compared to those who are greater than 85 years old.

There are many different conditions that have an appearance very similar to Merkel cell carcinoma. These include epidermoid cysts, squamous cell carcinoma, basal cell carcinoma, pyogenic granuloma, lipomas, adnexal tumors, sebaceous cysts, melanoma and lymphoma. Under a microscope, small cell carcinoma of the lung is often a difficult disease to differentiate from primary Merkel cell carcinoma. Both cancers have similar neuroendocrine features. As such, special stains must be carried out in order to distinguish one cancer form from the other. This procedure is called immunostaining. During immunostaining, antibodies are applied to a sample of the tumor from a biopsy or from surgical removal. The antibodies are used to test for certain proteins (markers). Typically, MCC tumors stain positive for low molecular weight cytokeratins (CAM 5.2 or AE1/AE3), CK20 and neuron-specific enolase (NSE). MCC is typically not positive for CK7 or thyroid transcription factor 1 (TTF-1).


MERRF Syndrome

肌阵挛性癫痫伴破碎红纤维综合征

myoclonic epilepsy associated with ragged red fibers

Symptoms of MERRF syndrome can begin in childhood, adolescence or early adulthood after a period of normal early development. Signs, symptoms and physical findings associated with MERRF syndrome may vary greatly between affected individuals in the same family and between different families. The age of onset and how quickly the condition progresses can differ between individuals.

MERRF syndrome is caused by genetic changes (mutations) in mitochondrial DNA (mtDNA). Mitochondria, which are found by the hundreds or thousands in the cells of the body, particularly in muscle and nerve tissue, carry the blueprints for regulating energy production. MtDNA encodes specific genes that are the instructions for making some of the essential parts of the mitochondria.

MERRF syndrome is a rare disorder that affects males and females in equal numbers. Onset of symptoms of MERRF syndrome can occur in childhood, adolescence or early adulthood. It typically presents after a period of normal early development.

MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) syndrome is a disorder that begins in childhood and affects mostly the nervous system and muscle. The most common early symptoms are seizures, recurrent headaches, loss of appetite and recurrent vomiting. Stroke-like episodes with temporary muscle weakness on one side of the body (hemiparesis) may also occur and this can lead to altered consciousness, vision and hearing loss, loss of motor skills and intellectual disability. Diabetes mellitus and paralysis of eye muscle (chronic progressive external ophthalmoplegia) are often present in isolation or in association with other symptoms. MELAS is caused by mutations in mitochondrial DNA (mtDNA). Some mutations that cause MELAS are found in mtDNA genes that are also associated with MERRF syndrome. In one patient, this syndrome has been associated with mutations in a nuclear gene, POLG1. (For more information on this disorder, choose MELAS as your search term in the Rare Disease Database.)

MERRF syndrome is diagnosed based on clinical findings and molecular genetic testing.


Mesenchymal Chondrosarcoma

Mesenchymal chondrosarcoma is an extremely rare, often aggressive form of cancer. It is an uncommon type of chondrosarcoma. Conventional chondrosarcoma is a form of bone cancer that arises from cartilage cells. Cartilage is the specialized tissue that serves as a buffer or cushion at joints. Most of the skeleton of an embryo consists of cartilage, which is slowly converted into bone. Approximately two-thirds of cases of mesenchymal chondrosarcoma affect the bones, especially the spine, ribs or jaws. The remaining cases occur in areas of the body other than bone (extraskeletal, that is, occurring in soft tissues like muscle and fat). Unlike conventional chondrosarcomas, mesenchymal chondrosarcomas occur with greater frequency in young adults. This form of cancer often spreads (metastasizes) to other areas of the body and can cause life-threatening complications.

The symptoms of mesenchymal chondrosarcoma may vary depending upon the exact location and progression of the tumor. Most mesenchymal chondrosarcomas arise in the bones of the jaw, spine or the ribs. However, the tumor can arise almost anywhere within the body. The arms and legs are also frequent sites of tumor development, especially the main bone of the thigh (femur). Approximately one-third of cases occur outside of bone, appearing as soft tissue masses and can affect the muscle or central nervous system

The exact cause of mesenchymal chondrosarcoma is unknown. Investigators are conducting ongoing basic research to learn more about the many factors that may result in cancer. No identifiable risk factors for the development of mesenchymal chondrosarcoma have been discovered.

Mesenchymal chondrosarcoma was first described in the medical literature in 1959. It is an extremely rare form of cancer; fewer than 800 cancers have been reported in the medical literature. This tumor is most common in children and young adults (aged 10-30), but can affect individuals of any age including young children and older adults. Females are affected slightly more often than males. Mesenchymal chondrosarcoma is more likely to occur outside the bone in young adults or children and to affect bone in older adults. Mesenchymal chondrosarcomas account for approximately 5-10 percent of all cases of chondrosarcoma.

Symptoms of the following disorders can be similar to those of mesenchymal chondrosarcoma. Comparisons to other sarcomas of bone or soft tissue may be useful to understand the place of this diagnosis better.

A diagnosis of mesenchymal chondrosarcoma may be difficult. Some individuals may seek attention because of pain and swelling. A diagnosis may be made based upon a thorough clinical examination, a detailed patient history and a variety of specialized tests including x-ray studies and a procedure in which a small sample of tissue is removed and studied under a microscope (biopsy). A biopsy of a tumor or mass determines what type of cancer is present by identifying the cell type that makes up the tumor. In individuals suspected of a mesenchymal chondrosarcoma an open biopsy or a needle-guided biopsy is recommended.


IgG4-related mesenteritis

In general, mesenteric panniculitis is a chronic, benign disorder with a favorable prognosis that occasionally resolves on its own (spontaneous regression). Nonetheless, symptoms of mesenteric panniculitis may be severe in some patients and can result in significant effects on quality of life. The clinical presentation of mesenteric panniculitis is highly variable. Some patients have few or no noticeable symptoms. The diagnosis of mesenteric panniculitis may be made incidentally following a CT scan of the abdomen, generally for the evaluation of abdominal pain. Symptoms of mesenteric panniculitis fall into two categories. Some symptoms, such as abdominal pain, are due to the mass-like effect of mesenteric inflammation, and potentially involvement of adjacent structures including the small intestine. The second group of symptoms occurs in the presence of chronic inflammation and may include weight loss, fever, and fatigue. Some affected individuals may develop complications such as small bowel obstruction or acute abdomen. Small bowel obstruction prevents the passage of food through the intestines and can cause a variety of nonspecific gastrointestinal symptoms as well as a nutrient malabsorption.

There is little information available on the cause of mesenteric panniculitis. Many autoimmune diseases are believed to occur when patients with genetic predisposition to the diseases are exposed to an environmental factor that triggers an inappropriate immunologic response. This response ultimately leads to chronic inflammation. To this end, many conditions have been associated with and possibly predispose to the development of mesenteric panniculitis. These include surgery, acute pancreatitis, other autoimmune conditions and trauma.

The epidemiology of mesenteric panniculitis has not been fully defined. One study reported that findings consistent with mesenteric panniculitis occurred in 359 patients (0.24%) from a total of 147,794 abdominal computed tomography (CT) examinations undertaken for over a 5-year period in a large community based medical system. Of these, 100 patients (28%) had known malignancy or were later diagnosed with cancer. The incidence of mesenteric panniculitis from recent studies has shown a range from 0.16% – 3.4%. This range is dependent on the method of diagnosis and whether it is histologic versus radiologically diagnosed.

Symptoms of mesenteric panniculitis mimic those of a number of other benign and malignant conditions. Because of this, it is important to rule out other diseases prior to confirming the diagnosis of mesenteric panniculitis. Infectious causes range from viral, bacterial (including V. cholerae) and parasitic infections. There are also a variety of diseases that are associated with mesenteric abnormalities on abdominal imaging. Such conditions include primary or metastatic mesentery cancer, gastrointestinal lymphoma, desmoid tumors, inflammation of the pancreas (pancreatitis), Crohn’s disease, idiopathic nodular panniculitis, locally advanced pancreatic adenocarcinoma, retroperitoneal fibrosis and other sclerotic diseases as mentioned above.

The diagnosis of mesenteric panniculitis is made based upon identification of suggestive symptoms, a detailed patient history, and a thorough clinical evaluation.


Metachromatic leukodystrophy

Each MLD subtype has specific symptoms and rate of progression. Each subtype is based on age of onset.

MLD is an autosomal recessive genetic disorder. Recessive genetic disorders occur when both copies of the gene are affected. If a child is affected, most of the time, their parents are carriers, meaning each parent will have one changed (mutated) copy and one normal copy of the ARSA gene, but will not have symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25%. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females. The ARSA gene encodes the protein arylsulfatase A. There is some association with specific mutations and the subtype of MLD (genotype-phenotype correlation). Rarely, children with MLD have working copies of the ARSA gene, but abnormalities in PSAP gene, which encodes several saposin proteins, including saposin B, an activator of arylsulfatase A.

The true prevalence rate of MLD is unknown, but is estimated to be between 1 in 40,000 and 1 in 160,000. The Navajo also have a higher prevalence rate of 1 in every 2,500 people. In certain populations in the Middle East, these numbers may be even higher.

There are multiple related disorders that have been identified with similar causes or symptoms, including other leukodystrophies, which can have a similar initial presentation in early childhood.

MLD is first suspected by recognizing the characteristic pattern of progressive impairment. In the late-infantile form, the first signs are often difficult walking, which can present as new inability to fully lift the feet while walking (foot drop) or by toe walking. For adult MLD, the first signs are slurred speech and behavioral issues that include difficulty in school, behavior changes, and decreased ability in school. Individuals with juvenile MLD can present with motor or cognitive symptoms.


干骺软骨发育异常Schmid型

Metaphyseal Chondrodysplasia, Schmid Type

Japanese type spondylometaphyseal dysplasia

Metaphyseal chondrodysplasia, Schmid type (MCDS), is a very rare inherited disorder characterized by short stature with abnormally short arms and legs (short-limbed dwarfism) and bowed legs (genu varum). Other physical characteristics may include outward flaring of the bones of the lower rib cage, lumbar lordosis, pain in the legs, and/or hip deformities in which the thigh bone is angled toward the center of the body (coxa vara). Such abnormalities of the legs and hips typically result in an unusual waddling walk (gait). MCDS is transmitted as an autosomal dominant trait.

In MCDS, portions of the bones of the arms and legs develop abnormally with unusual cartilage formations and subsequent abnormal bone formation at the large end portions (metaphyses) of the long bones. Bone growth normally takes place at the metaphyses, but in individuals with MCDS, the growth plate does not function as well as normal and the bones of the leg bow. Consequently, affected individuals exhibit unusually short arms and legs and short stature (short-limbed dwarfism) that usually become apparent by the second year of life.

MCDS is caused by a mutation of the gene for type X collagen called COL10A1. This gene has been mapped to chromosome 6q21-22.3. MCDS is transmitted as an autosomal dominant trait.

Metaphyseal chondrodysplasia Schmid type is a very rare bone disorder that affects males and females in equal numbers. Individuals of several large families (kindred) have been documented in the medical literature.

Symptoms of the following disorders can be similar to those of Schmid type metaphyseal chondrodysplasia. Comparisons may be useful for differential diagnosis:

McKusick type metaphyseal chondrodysplasia, also known as cartilage-hair hypoplasia, is an extremely rare inherited disorder characterized by unusually fine, sparse hair and abnormal development of the cartilage and subsequent bone formation in the long bones of the arms and legs (metaphyseal chondrodysplasia), resulting in unusually short arms and legs and short stature (short-limbed dwarfism). Most affected individuals exhibit impairment of certain white blood cells (T-cells) that play an important role in helping the body’s immune system fight certain infections (cellular immunodeficiency). In addition, affected individuals may also exhibit impaired absorption of certain necessary nutrients (malabsorption); abnormally low levels of certain white blood cells in the body (neutropenia and lymphocytopenia); low levels of circulating red blood cells (anemia); increased susceptibility to repeated infections, such as chickenpox; abnormalities of the teeth; and/or other physical findings. The range and severity of symptoms vary widely from person to person. McKusick type metaphyseal chondrodysplasia is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose McKusick type metaphyseal chondrodysplasia as your search term in the Rare Disease Database.)


Metatropic Dysplasia I

Metatropic Dysplasia I is a rare genetic disorder characterized by extremely small stature, with short arms and legs. Other characteristics of this disorder are a narrow thorax, short ribs, and kyphoscoliosis (backward and sideways curvature of the spinal column) which develops into short trunk dwarfism.

Metatropic Dysplasia I is characterized by abnormal skeletal development. Patients with this disorder typically have short ribs, short deformed arms and legs, kyphoscoliosis (abnormal curvature of the spine) and extremely short stature.  A long narrow thorax, bulging joints with limited mobility of the knees and hips, and unusual increased extension of the finger joints are typical features.

Metatropic Dysplasia I can be inherited as an autosomal dominant or autosomal recessive trait.

Metatropic Dysplasia I is a very rare disorder that affects males and females in equal numbers.

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

Kniest Syndrome is a rare type of dwarfism that is characterized by unusually short arms and legs, a round face with hollow or depressed areas, swelling and stiffness of the joints, and a stiff drawing up (contractures) of the fingers.  A cleft palate, curvature of the spine (scoliosis), vision and hearing problems may also occur.  (For more information on this disorder, choose Kniest as your search term in the Rare Disease Database.)

Treatment of Metatropic Dysplasia I is symptomatic and supportive. When partial dislocation of the segments of the spinal column at the top of the spine (cervical vertebrae) is present, the joint between the two vertebrae can be fused together. This procedure should be done in order to prevent damage to the cervical part of the spinal cord.


Methylmalonic Acidemia

维生素B12反应性甲基丙二酸血症

Methylmalonic acidemia (MMA) is a group of genetic disorders in which the body can’t breakdown (metabolize) proteins and fats properly. This results in an abnormally high level of acid in the blood (acidemia) and body tissues. This condition varies in severity from mild to life-threatening. Infants with this condition typically have drowsiness, vomiting, dehydration, weak muscle tone (hypotonia) and excessive tiredness (lethargy). Without treatment, MMA can lead to coma and death in some patients. MMA is inherited in an autosomal recessive pattern.

The onset of MMA is usually during the first few months of life, but onset throughout childhood has been described. Babies may appear normal at birth, but develop symptoms once they start eating more protein, which can cause the condition to get worse.

Methylmalonic academia is caused by changes (variants) in several different genes including MMUT, MMAA, MMAB, MMADHC and MCEE.

Methylmalonic acidemia occurs in 1 in 50,000 to 1 in 100,000 livebirths. Based on a large study, the detection of MMA was below 2 cases per 100,000 newborns in North America, Europe and Asia-Pacific regions.

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

Methylmalonic acidemia can be identified at birth on a blood spot through expanded newborn screening with tandem mass spectrometry. A baby with high levels of acylcarnitines, methylmalomic acid and methylcitiric acid may have MMA. Additional testing on blood, urine and sometimes skin is needed to confirm a diagnosis of MMA. Magnetic resonance imaging (MRI) and computed tomography (CT) imaging studies show several alterations in the brain. Genetic testing for variants in the MMUT, MMAA, MMAB, MMADHC and MCEE genes can also confirm the diagnosis.


Mevalonate kinase deficiency

Mevalonate kinase deficiency (MKD) is a rare genetic autoinflammatory disorder. Autoinflammatory syndromes are a group of disorders characterized by seemingly random or unprovoked episodes of inflammation generally due to an abnormality of the innate immune system. They are not the same as autoimmune disorders, in which the adaptive immune system malfunctions and mistakenly attacks healthy tissue.

Mevalonate kinase deficiency is a spectrum of disease that can range from milder symptoms to severe, even life-threatening complications. Affected individuals can fall anywhere along this spectrum and it is important to remember every person is unique and the disorder may affect them differently from how it affects another person.

Mevalonate kinase deficiency is caused by changes (mutations) in the MKV 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 specific protein, this can affect many organ systems of the body.

Mevalonate kinase deficiency affects males and females in equal numbers. More than 300 individuals worldwide are known to have the disorder, but the true number is likely greater. Most people with the disorder are individuals of western European heritage with approximately 60% occurring in Dutch or French individuals. The exact incidence and prevalence is unknown and it is likely that the disorder goes misdiagnosed or undiagnosed. This makes it difficult to determine the exact incidence or prevalence of mevalonate kinase deficiency in the general population.

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

A diagnosis of a mevalonate kinase deficiency is made based upon a thorough clinical evaluation, identification of characteristic symptoms (e.g., lifelong recurrent fevers not due to infection), and a variety of tests including blood tests to determine the levels of immunoglobulin D (IgD) in the blood, urine tests to detect the presence of mevalonate kinase, and DNA analysis to detect the genetic mutation associated with the disorder.

Treatment is directed toward the specific symptoms that are apparent in each individual.