Isovaleric acidemia

isovaleric acid CoA dehydrogenase deficiency

Isovaleric acidemia is a rare metabolic disorder that ranges in severity from asymptomatic to mild or life-threatening symptoms depending on the mutation and factors predisposing acute attacks. Two major clinical scenarios are often described, an acute form and a chronic intermittent form, but in reality the disease is best thought of as a continuous spectrum from asymptomatic to life threatening. A characteristic ‘sweaty feet’ odor is often present in patient sweat or cerumen due to a buildup of isovaleric acid. Patients may develop aversion early to protein-rich foods.

Isovaleric acidemia is a genetic disorder inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. 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 working genes from both parents is 25%. The risk is the same for males and females.

Isovaleric acidemia is a rare disorder that presents either soon after birth or during infancy. It may present up to adolescence. It affects an equal number of males and females. The prevalence of this condition is 1 per 526,000 in Western populations and the incidence is 1 per 250,000 in the US.

Organic acidemias are a group of disorders in which there is a genetic mutation in genes for enzyme(s) responsible for breaking down amino acids. There is an accumulation of organic acid metabolites that cause symptoms in a patient. Many organic acidemias present similarly, including during acute attacks, often in the neonatal period. Below are examples of some organic acidemias.

In the United States and some developed countries, isovaleric acidemia is routinely identified by newborn screening through a blood test called tandem mass spectrometry, often designated as MS/MS. In other countries, the diagnosis must be suspected clinically before it can be diagnosed. Laboratory studies that can be useful in symptomatic patients include checking for high levels of acid and ketones (ketoacidosis) in blood, high levels of glycine in the blood or urine (hyperglycinemia and hyperglycinuria), high levels of ammonia (hyperammonemia), or low levels of certain white blood cells (neutropenia), platelets (thrombocytopenia) or all blood cell types (pancytopenia). The diagnosis is then confirmed by DNA testing. Less commonly, certain types of cells from the body (white blood cells, skin cells) may be sampled from the patient and tested to confirm decreased or deficient activity of the enzyme isovaleryl-CoA dehydrogenase.


Right sided atrial isomerism

Ivemark syndrome is a rare disorder that affects multiple organ systems of the body. It is characterized by the absence (asplenia) or underdevelopment (hypoplasia) of the spleen, malformations of the heart and the abnormal arrangement of the internal organs of the chest and abdomen. The symptoms of Ivemark syndrome can vary greatly depending upon the specific abnormalities present. Many infants have symptoms associated with abnormalities affecting the heart including bluish discoloration to the skin due to a lack of oxygen in the blood (cyanosis), heart murmurs, and signs of congestive heart failure. Ivemark syndrome often causes life-threatening complications during infancy. The exact cause of Ivemark syndrome is not known.

The symptoms of Ivemark syndrome are due to the abnormal arrangement and malformation of certain internal organs. The organs of the chest and abdomen normally develop with specific left-right asymmetry, which means that the internal organs on the left side of the body are different than those on the right. In Ivemark syndrome, there are several characteristic findings involving the internal organs of the chest and abdomen including misplacement of the liver near the center of the body, abnormal positioning of the intestines (intestinal malrotation), and severe underdevelopment (hypoplasia) or absence (asplenia) of the spleen. Ivemark syndrome may also be known as right isomerism sequence because the left side of the body is identical to the right. For example, the right and left sides of the heart and lungs, which normally are distinct, may not be clearly defined.

The exact cause of Ivemark syndrome is unknown. Most cases seem to occur randomly for no apparent reason (sporadic cases). Researchers believe that multiple factors (e.g., genetic and environmental) play a role in the development of the disorder. Ivemark syndrome has occurred in multiple members of the same family suggesting that an inherited genetic predisposition may have been a factor in the development the disorder in these cases.

According to the medical literature, Ivemark syndrome affects boys more often than girls. The exact incidence of Ivemark syndrome is unknown. The incidence of laterality disorders taken together is estimated to be 1 in 15,000 people in the general population.

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

A diagnosis of Ivemark syndrome is made based upon a detailed patient history, a thorough clinical evaluation, identification of characteristic symptoms and a variety of specialized tests. Blood samples may be taken to detect the presence of Howell-Jolly bodies, which are small fragments of DNA found in red blood cells that indicate problems with the function of the spleen (or the lack of a spleen). In addition, a test that uses sound waves to make a picture of the heart (echocardiogram) can confirm the presence and severity of heart defects.


Jackson-Weiss syndrome

craniosynostosis, midfacial hypoplasia and foot abnormalities

JWS is typically characterized by craniofacial malformations occurring in association with skeletal abnormalities of the feet, but some affected individuals have no craniofacial abnormalities. The range and severity of associated findings may vary greatly among members of the same or other affected families.

JWS is caused by variants in the FGFR2 gene. The FGFR2 gene regulates the production of a protein known as a fibroblast growth factor receptor (FGFR). One of the many functions of this protein is to signal immature cells to become bone cells during embryonic development. Gene variants that disrupt the functioning of these proteins may result in certain abnormalities such as premature fusion of the craniofacial area and the limbs.

JWS appears to affect males and females in equal numbers. The incidence rate is unknown.

Symptoms of the following disorders can be like those of Jackson-Weiss syndrome. Comparisons may be useful for a differential diagnosis:

Apert syndrome is a rare disorder inherited in an autosomal dominant pattern. This disorder is characterized by fused or webbed fingers and toes (syndactyly), a pointed head (acrocephaly or oxycephaly), other skeletal and facial abnormalities and intellectual disability. (For more information on this disorder, choose Apert syndrome as your search term in the Rare Disease Database.)


干骺端软骨发育不良，Jansen型

Jansen Type Metaphyseal Chondrodysplasia

Jansen type metaphyseal chondrodysplasia is an extremely rare progressive disorder in which portions of the bones of the arms and legs develop abnormally with unusual cartilage formations and subsequent abnormal bone formation at the large (bulbous) end portions (metaphyses) of these long bones (metaphyseal chondrodysplasia). As a result, affected individuals exhibit unusually short arms and legs and short stature (short-limbed dwarfism), findings that typically become apparent during early childhood. Abnormal cartilage and bone development may also affect other bones of the body, particularly those of the hands and feet (i.e., metacarpals and metatarsals). Infants with Jansen type metaphyseal chondrodysplasia may also have characteristic facial abnormalities and additional skeletal malformations. During childhood, affected individuals may begin to exhibit progressive stiffening and swelling of many joints and/or an unusual waddling gait and squatting stance. In addition, affected adults may eventually develop abnormally hardened (sclerotic) bones especially in the back of the head (cranial bones), which, in some cases, may lead to blindness and/or deafness. In addition, affected individuals have abnormally high levels of calcium in the blood (hypercalcemia). The range and severity of symptoms may vary from person to person. Most cases of Jansen type metaphyseal chondrodysplasia occur randomly as the result of a spontaneous genetic change (i.e., new genetic mutation).

In Jansen type metaphyseal chondrodysplasia, an extremely rare progressive disorder, portions of the bones of the arms and legs develop abnormally with unusual cartilage formations and subsequent abnormal bone formation at the large (bulbous) end portions (metaphyses) of these long bones (metaphyseal chondrodysplasia). As a result, affected individuals exhibit unusually short arms and legs and short stature (short-limbed dwarfism), findings that typically become apparent during childhood. Abnormal cartilage development and bone formation may also affect other bones of the body, including those of the hands and feet (i.e., metacarpals and metatarsals). As affected individuals age, abnormal cartilage formations in affected areas may harden into rounded (bulbous) masses of bone, which may become prominent.

The gene that is probably involved in most cases of Jansen type metaphyseal chondrodysplasia associated with hypercalcemia is located on the short arm (p) of chromosome 3 (3p21.1-p22). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males, and two X chromosomes for females. Each chromosome has a short arm designated as p and a long arm identified by the letter q. In order for researchers to clearly refer to the thousands of genes that may be present on one chromosome, both the long arm and short arm of each chromosome are divided into many bands that are numbered.

Jansen type metaphyseal chondrodysplasia is an extremely rare disorder that affects males and females in equal numbers. Approximately 20 cases have been reported in the medical literature.

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

Hypochondroplasia is a rare inherited skeletal disorder characterized by short stature with abnormally short arms and legs (short-limbed dwarfism) and an unusually long trunk (thorax and abdomen). Major symptoms may include bowing of the legs, abnormally short, broad fingers and toes (brachydactyly), mild limitation of elbow movements, and/or abnormal backward curvature of the spine (lordosis). In addition, affected infants may exhibit abnormalities of the head and face (craniofacial) area including drooping of the upper eyelids (ptosis), an abnormally prominent forehead (frontal bossing), and/or an unusually large head (macrocephaly). Hypochondroplasia is inherited in an autosomal dominant pattern. (For more information on this disorder, choose Hypochondroplasia as your search term in the Rare Disease Database.)


Small bowel atresia

Jejunal atresia is a rare type of obstruction of the small bowel affecting newborns. Patients with this disorder are born with a complete mechanical obstruction of the proximal small intestine. The obstruction may be caused by a membrane across the lumen of the bowel (type 1) or a complete gap in the bowel (types 2 and 3). In type 3b, in addition to a gap, the jejunum folds up against one of the arteries that supply blood to distal small bowel and proximal large bowel (the ileo-colic artery and marginal artery) so that the bowel coils up in a manner that looks like an apple peel or Christmas tree. This is sometimes also called maypole bowel or pagoda bowel.

Jejunal atresia affects the passage of material through the small intestine. Symptoms in individuals with this disorder include poor feeding, vomiting bile, a swollen abdomen, and constipation.

Jejunal atresia occurs sporadically for unknown reasons in fetuses that are generally normal in all other respects. The best theory to explain what happens is that the blood flow to a segment of the bowel is cut off with the result that the affected segment disappears leaving a gap in the bowel.

Jejunal atresia affects male and female newborns in equal numbers.

Symptoms of the following disorder can be similar to those of jejunal atresia. Comparisons may be useful for a differential diagnosis:

Duodenal atresia is a rare disorder in which there is a blockage of the normal opening in the first division of the small intestine, the duodenum. This malformation causes excessive accumulation of amniotic fluid before birth and vomiting of the neonate immediately after birth. Other symptoms of this disorder may be: a swollen upper abdomen; a yellowish coloring of the skin (jaundice). The obstruction can be repaired with surgery.

Surgery to repair the intestinal obstruction is performed as soon as possible after delivery. A section of the intestine including the atresia will be removed and the two ends will be sewn together. Food is given by a vein but not by mouth (parenteral nutrition) for a period of time before and after surgery until proper function of the intestine is established.


Jervell and Lange-Nielsen syndrome

autosomal recessive long QT syndrome (LQTS)

Symptoms of JLNS are usually apparent during early childhood. Hearing loss is detected at birth or during early childhood. Hearing loss associated with JLNS is caused by the inability of the auditory nerves to transmit sensory information to the brain (sensorineural hearing loss) and affects both ears (bilateral). In JLNS hearing loss is usually profound, but it tends to affect the hearing of high frequencies more than low frequencies. Low levels of iron and increased levels of gastrin are often present in patients with JLNS, possibly leading to iron deficient anemia.

Researchers have determined that most cases of JLNS are caused by disruptions or changes (mutations) of one of two different genes (KCNQ1 or KCNE1). Most of these mutations result in the truncation, or premature shortening of the protein length. This results in a dysfunctional protein. More than 90 percent of cases of JLNS are caused by mutations of the KCNQ1 gene. These two genes produce (encode) proteins essential to the function of the ion channels of the heart and the snail-like tube that forms part of the inner ear (cochlea). Ion channels regulate the movement of electrically charged particles (e.g., potassium and sodium ions) in certain structures of the ear and heart. These ions carry electrical impulses necessary for hearing and the normal function of the heart. Mutations of these genes result in abnormal function of the ion channels and, in turn, affect hearing and the proper function of the heart’s electrical system.

JLNS affects males and females in equal numbers, but females seem to have a lower number of life-threatening events. JLNS is generally present in early childhood with a 90% chance of symptomatic problems by the age of 18. The prevalence of the disorder is 1 to 6 people per 1,000,000 live births. The disorder has a higher prevalence in Norway as well as Sweden (both are 1 in 200,000).

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

Romano-Ward syndrome (RWS) is a rare genetic heart disorder characterized by abnormalities affecting the electrical system of the heart that result in long QT syndrome. The severity of RWS varies greatly from patient to patient. Some individuals may have no apparent symptoms (asymptomatic); others may develop abnormally increased heartbeats (tachyarrhythmias) resulting in episodes of unconsciousness (syncope), cardiac arrest, and potentially sudden death. RWS is inherited as an autosomal dominant trait. (For more information on this disorder, choose Romano-Ward as your search term in the Rare Disease Database.)


Johanson-Blizzard syndrome

Johanson-Blizzard syndrome (JBS) is an extremely rare genetic disorder that affects multiple organ systems of the body. Many symptoms are present at birth (congenital) or early childhood. The spectrum of potential features and physical findings associated with JBS is wide and varied and can differ dramatically from one person to another. However, characteristic features include insufficient intestinal absorption (malabsorption) of fats and other nutrients due to abnormal development of the pancreas (pancreatic insufficiency); failure to grow and gain weight at the expected rate (failure to thrive) during the first years of life, contributing to short stature; abnormalities of permanent teeth; distinctive abnormalities of the skull and facial (craniofacial) region including a small beak-shaped nose; and/or varying degrees of intellectual disability. JBS is caused by mutations to the UBR1 gene. This genetic mutation is inherited as an autosomal recessive trait.

The features and physical findings associated with JBS can vary greatly from one person to another. It is important to note that affected individuals may not have all of the symptoms discussed below. However, pancreatic insufficiency, tooth abnormalities, and a characteristic shape of the nose are found in almost all affected individuals. The severity of JBS can vary as well and some infants may develop life-threatening complications during infancy. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.

JBS is caused by mutations of the ubiquitin E3 ligase (UBR1) gene. This genetic mutation is inherited as an autosomal recessive trait.

JBS affects males and females in equal numbers. Although the exact incidence is unknown, the frequency has been estimated to be 1 in 250,000 births. More than 60 cases have been described in the medical literature. JBS was first described in the medical literature in 1971 by doctors Johanson and Blizzard. The defective gene was identified by Zenker, et al. in 2006.

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

A diagnosis of may be suspected based upon identification of characteristic symptoms (e.g., distinctive beak-shaped nose, exocrine pancreatic insufficiency, tooth abnormalities, scalp defects, deafness), a thorough clinical evaluation and a detailed patient history. A diagnosis of JBS can be confirmed through molecular genetic testing, which can identify characteristic mutations of the UBR1 gene that cause the disorder.


Joubert syndrome

Many of the clinical symptoms of Joubert syndrome are apparent in infancy and most affected children have delays in gross motor milestones. The most common features are lack of muscle control (ataxia), abnormal breathing patterns (hyperpnea), sleep apnea, abnormal eye and tongue movements and low muscle tone. Intellect ranges from normal to severe intellectual disability. Joubert syndrome is characterized by a specific finding on an MRI called a molar tooth sign in which the cerebellar vermis of the brain is absent or underdeveloped and the brain stem is abnormal.

More than thirty genes have been identified that cause Joubert syndrome. The proteins produced from these genes are known or suspected to play roles in cell structures called primary cilia. Primary cilia are microscopic, finger-like projections that stick out from the surface of cells and are involved in sensing the physical environment and in chemical signaling. Primary cilia are important for the structure and function of many types of cells, including brain cells (neurons) and certain cells in the kidneys and liver. Primary cilia are also necessary for the perception of sensory input, which is interpreted by the brain for sight, hearing, and smell.

The birth prevalence of JS is estimated to be between 1/80,000 and 1/100,000 live births, but JS may be underdiagnosed and the true prevalence may be higher.

Several conditions have been described in which the molar tooth sign and characteristics of Joubert syndrome are present in addition to other findings. The term Joubert syndrome and related disorders.was used in the past to describe these conditions. The following conditions were once thought to be distinct syndromes, but are now considered to be part of the spectrum of Joubert syndrome:

Dandy-Walker malformation is a rare malformation of the brain that is present at birth (congenital). It is characterized by an abnormally enlarged space at the back of the brain (cystic 4th ventricle) that interferes with the normal flow of cerebrospinal fluid through the openings between the ventricle and other parts of the brain. Excessive amounts of fluid accumulate around the brain and cause abnormally high pressure within the skull, swelling of the head (congenital hydrocephalus) and neurological impairment. Motor delays and learning problems may also occur. Dandy-Walker malformation is a form of obstructive or internal non-communicating hydrocephalus, meaning that the normal flow of cerebrospinal fluid is blocked resulting in the widening of the ventricles. (For more information, choose Dandy Walker as your search term in the Rare Disease Database.)


Juvenile CLN3 Disease

神经元蜡样脂褐质沉积症3型

The symptoms of juvenile CLN3 disease usually become apparent between 5 and 15 years of age, usually with visual abnormalities that progresses rapidly. Affected children also suffer from problems with their speech, cognitive decline, behavioral changes, and motor decline.

Juvenile CLN3 disease occurs because of disruptions or changes (mutations) of the CLN3 gene located on the short arm (p) of chromosome 16 (16p12.1). The function of the protein encoded by this gene is not yet understood.

Juvenile CLN3 disease affects males and females in equal numbers. In the United States, juvenile CLN3 disease along with the other forms of neuronal ceroid lipofuscinoses, occurs in approximately three in 100,000 births. It can occur with greater frequency in families of Northern European Scandinavian ancestry; in particular, those of Swedish heritage. It is thought to occur in one in 25,000 infants in northern Europe. Juvenile CLN3 disease is one of the most common neurodegenerative disorders affecting children.

Symptoms of the following disorders can be similar to those of juvenile CLN3 disease. Comparisons may be useful for a differential diagnosis.

A diagnosis of juvenile CLN3 disease may be made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic physical findings, and a variety of specialized tests including the microscopic examination (i.e., electron microscopy) and study of the chemical components (histochemical examination) of samples of tissue (biopsy), usually from the skin. The study of such tissue samples reveals abnormal accumulations of deposits (i.e., pigmented lipids [lipopigments] ceroid and lipofuscin) in membrane-bound cavities within the body (cytoplasm) of cells (inclusion bodies). In juvenile CLN3 disease these have a characteristic appearance rather like fingerprints. Similar deposits may also be present in other tissues and cells of the body (e.g., certain white blood cells [lymphocytes].


HJV or HAMP-related hemochromatosis

Juvenile hemochromatosis is a rare genetic disorder characterized by the accumulation of iron in various organs of the body. Symptoms usually become apparent before the age of 30, though they may appear at a later age in some individuals. The specific symptoms and severity of juvenile hemochromatosis vary from one person to another. Common symptoms include absent or decreased function of the testes in males or ovaries in females (hypogonadotropic hypogonadism), heart (cardiac) disease, scarring of the liver (cirrhosis), joint disease, diabetes and dark discoloration of patches of skin (hyperpigmentation). If untreated, juvenile hemochromatosis can potentially cause life-threatening complications. Juvenile hemochromatosis is caused by mutations in one of two genes (HJV and HAMP). Juvenile hemochromatosis is inherited in an autosomal recessive manner.

The symptoms and severity of juvenile hemochromatosis can vary from one person to another, even within the same family. Major symptoms include hypogonadotropic hypogonadism and heart, liver and joint disease. In some patients, nonspecific, vague symptoms may precede the development of more serious complications. These earlier symptoms may include fatigue, joint pain (arthralgia) and lack of appetite. If left untreated, juvenile hemochromatosis can cause serious, life-threatening complications.

Juvenile hemochromatosis is a genetic condition inherited in an autosomal recessive manner. Juvenile hemochromatosis is caused by mutations in HJV and HAMP. Individuals have two copies of the HJV gene and the HAMP gene, one copy from the sperm and one copy from the egg. Juvenile hemochromatosis type 2A occurs when a child inherits two altered (or mutated) copies of HJV, and therefore has no normal copy of the gene. Juvenile hemochromatosis type 2A is more common, accounting for 90 percent of known cases of juvenile hemochromatosis. Juvenile hemochromatosis type 2B occurs when a child has two altered copies of HAMP.

Juvenile hemochromatosis affects males and females in equal numbers. The disorder is rare, but the actual incidence in the general population is unknown. Juvenile hemochromatosis has been reported worldwide. The disorder typically becomes apparent between 10-30 years of age. Mutations of the HJV gene account for the majority (~90%) of cases of juvenile hemochromatosis.

There are several conditions with overlapping laboratory findings or symptoms of juvenile hemochromatosis. These conditions are primary disorders of iron overload, a group of disorders characterized by iron accumulation in the body. Symptoms common among primary disorders of iron overload include fatigue, abdominal pain, lack of sex drive, joint pain and heart abnormalities, though the specific symptoms related to these disorders can vary depending upon the location and extent of iron accumulation. Besides juvenile hemochromatosis, primary disorders of iron overload include atransferrinemia, African iron overload disease, HFE-related hemochromatosis (classic hereditary hemochromatosis), TFR2-related hereditary hemochromatosis and ferroportin disease. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)

Early diagnosis and prompt treatment of juvenile hemochromatosis are essential and may help to prevent permanent organ damage and potentially life-threatening complications resulting from excessive iron storage. The disorder may be diagnosed based upon a thorough clinical evaluation; detection of certain physical findings (including hepatomegaly, diabetes mellitus, abnormal skin pigmentation, heart disease, hypogonadism, and/or arthritis), a thorough patient history; a complete family history and specialized tests.


Juvenile myelomonocytic leukemia

青少年型骨髓单核细胞白血病

chronic myelomonocytic leukemia of infancy

Although the symptoms below are common to JMML, affected children can potentially exhibit these symptoms in any combination. Among individual cases, the specific symptoms and signs can vary. Symptoms can develop over a period of weeks or months.

The exact underlying cause of JMML is unknown. Investigators are conducting ongoing basic research to learn more about the many factors that may result in cancer.

JMML accounts for ~ 2-3% of all childhood leukemias. The mean age at diagnosis is 2. Males are affected more often than females by a ratio of approximately 2:1. Studies conducted in Denmark and British Columbia placed the incidence at 1.2 cases per million in children each year. In the UK, a study found a lower incidence rate of 0.6 per million. Childhood leukemia as a whole is estimated to affect approximately 4,000 children each year in the United States.

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

A diagnosis of JMML is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A diagnosis of JMML is usually considered after other conditions have been ruled out.


Classic pilocytic astrocytoma

Juvenile pilocytic astrocytoma (JPA) is a rare childhood brain tumor. In most cases, the tumor is a benign, slow growing tumor that usually does not spread to surrounding brain tissue. Symptoms of a JPA will vary depending upon the size and location of the tumor. Most symptoms result from increased pressure on the brain and include headaches, nausea, vomiting, balance problems and vision abnormalities.

The symptoms associated with juvenile pilocytic astrocytomas vary depending upon the size and location of the tumor. A JPA can develop anywhere with the central nervous system (i.e., brain and spinal cord). Most cases arise in the lower area of brain near the back of the neck that controls movement and balance (cerebellum), the brainstem, the hypothalamic region or the optic nerve pathways.

The exact cause of juvenile pilocytic astrocytomas is unknown. Researchers speculate that genetic and immunologic abnormalities, environmental factors (e.g., exposure to ultraviolet rays, certain chemicals, ionizing radiation), diet, stress, and/or other factors may play contributing roles in causing specific types of cancer. Investigators are conducting ongoing basic research to learn more about the many factors that may result in cancer.

Juvenile pilocytic astrocytomas affect males and females in equal numbers. Most JPAs develop within the first two decades of life. JPAs are the most common cerebellar tumor in children. Astrocytomas as a whole are the most common brain tumor of childhood accounting for more than half of all primary childhood tumors of the central nervous system. The incidence rate is estimated at 14 new cases per million in children younger than 15 years of age. Most astrocytomas (approximately 80 percent) in children are low grade.

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

A diagnosis of juvenile pilocytic astrocytoma is made based upon a thorough clinical evaluation and a variety of specialized test, including various imaging techniques. Such imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues such as the brain. CT scanning and MRIs may also be to help evaluate the size, placement, and extension of the tumor and to serve as an aid for future surgical procedures.


Kabuki syndrome

Some features of Kabuki syndrome are present at birth (congenital). Other features become apparent as an affected child ages. The specific findings and the severity of those findings can vary from one person to another. A wide variety of findings affecting multiple organ systems of the body can potentially occur. It is important to note that affected individuals may not have all the features discussed below. Parents of an affected child should talk to their physician and medical team about their child’s specific case, associated features and overall prognosis.

In August of 2010, a group of researchers at the University of Washington reported that pathogenic variants in the gene KMT2D (formerly MLL2) were responsible for Kabuki syndrome in most affected individuals who were tested. In 2012, a group of researchers from Belgium identified a second gene, termed KDM6A, that causes Kabuki syndrome. Most cases of Kabuki syndrome, particularly those caused by variants of KMT2D, occur for the first time in the affected individual with no family history of the disorder (de novo). However, familial occurrence of Kabuki syndrome has been reported.

Kabuki syndrome affects males and females in equal numbers. The incidence of Kabuki syndrome is unknown but has been estimated to be somewhere between 1 in 32,000-86,000 individuals in the general population. More than 400 affected individuals who have genetically proven Kabuki syndrome have been reported in the medical literature. Although the disorder was first reported in Japan, Kabuki syndrome has since been reported in a wide variety of different ethnic groups.

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

International consensus diagnostic criteria for Kabuki syndrome have been published, which allow for a diagnosis to be made when a person has either a positive genetic testing result or a combination of certain clinical features.


Kallmann syndrome

idiopathic hypogonadotropic hypogonadism with anosmia

Kallmann syndrome (KS) is a rare genetic disorder in humans that is defined by a delay/absence of signs of puberty along with an absent/impaired sense of smell. A closely related disorder, normosmic idiopathic hypogonadotropic hypogonadism (nIHH), refers to patients with pubertal failure but with a normal sense of smell. Both KS and nIHH are due to an isolated deficiency of a key reproductive hormone called gonadotropin-releasing hormone (GnRH). KS and nIHH occurs in both sexes but males are more commonly diagnosed with this condition.

The clinical hallmark of IGD is the failure of onset of puberty. This lack of pubertal maturation, i.e. hypogonadism, occurs in both sexes and is characterized by reduced blood levels of the sex hormone levels (testosterone and estrogen) as well as gonadotropins (LH and FSH) and infertility. In boys, the onset of normal pubertal development is heralded by testicular enlargement that is then followed by penile growth and the appearance of pubic hair. Affected men complain of absence of secondary sexual characteristics (facial hair growth, body hair growth, decreased pubic hair growth and genital enlargement) and a delayed growth spurt in comparison to their peers. In addition, an absence of sexual interest (libido) and poor sexual function (inability to attain or sustain an erection) may also be present. Unusual growth of breasts may also be rarely seen in these subjects although this more typically occurs during treatment of this condition and is often transient (see below).

IGD is caused by mutations in a number of different genes and to-date, ~50% of patients have a demonstrable genetic mutation that is identifiable. While some genes primarily cause the KS form of IGD, others cause nIHH only, and some can cause both forms of this disorder. Mutations in genes that are thought to disrupt the development and migration of GnRH neurons from the olfactory epithelium to hypothalamus result in the KS phenotype. These include: KAL1, NELF, FGFR1, FGF8, PROK2, PROKR2, HS6ST1, CHD7, WDR11 and SEMA3A. Genes that primarily interfere with the normal secretion of GnRH (GNRH1, KISS1, KISS1R (GPR54), TAC3, TACR3) or its action on the pituitary (GNRHR) cause nIHH. The overlap genes ie. the ones that cause both KS and nIHH include FGFR1, FGF8, PROK2, PROKR2, HS6ST1, CHD7, WDR11 and SEMA3A. Presumably, these genes may have multiple roles in GnRH biology including both migration and their normal secretory function.

Both KS and nIHH are relatively rare, can affect both males and females, with a clear male predominance (~4:1). According to a recent retrospective study, to identify all diagnosed KS cases throughout Finland born during a defined time period, the minimal incidence of KS in Finland was approximately 1 in 48,000 newborns. There was a clear difference in estimates between boys (1 in 30,000) and girls (1 in 125,000). The reason for this sex ratio relates in part to the genetics and in part due to a bias of ascertainment wherein males with delayed puberty tend to seek care more frequently than do their female counterparts. A precise estimate of prevalence remains a challenge as there may be differences in different populations.

Occasionally, GnRH deficiency may present as adult-onset GnRH deficiency, wherein there is a history of an age-appropriate normal puberty followed by decrease in libido and fertility in adult life. These patients have usually normal testicular size and historical or physical evidence of normal spontaneous maturation, with documented fertility in several cases.

The diagnosis of Kallmann syndrome is based on the clinical evidence of arrested sexual maturation or hypogonadism and the incomplete sexual maturation by Tanner staging on physical examination. Tanner staging is an established way used during the physical examination by endocrinologists and pediatric endocrinologists worldwide to evaluate the maturation of the primary and secondary sexual characteristics:


Kasabach-Merritt phenomenon

Kasabach-Merritt phenomenon (KMP) is a rare condition that is associated with two rare vascular tumors: kaposiform hemangioendothelioma (KHE) and tufted angioma (TA). It is characterized by a coagulopathy with features including profound low platelets (thrombocytopenia), low fibrinogen (hypofibrinogenemia) and low level of red blood cells (anemia). The rare vascular tumors associated with this phenomenon usually occur in infants and young children and can be life-threatening secondary to the risk of bleeding and organ dysfunction.

Initially a vascular lesion is usually noted on the skin which can be firm and  hard (indurated). Areas of tiny red dots (petechiae) can appear around the lesion or on other parts of the body. If the vascular lesion is internal, these petechiae and bruising can be seen on the skin. Bruising and spontaneous bleeding can also occur. The tumors are not hemangiomas. They usually present in young infants, less than three months of age, but have also been reported in the toddler age group. These tumors occur in the extremities, chest, neck, abdomen and pelvis. They infiltrate across tissue and can be aggravated by interventions, infection and trauma. When the tumors associated with KMP are internal such as in the chest or abdomen, they can cause significant illness and can be life-threatening due to bleeding. Internal lesions can take a longer time to diagnose.

The cause of KMP is unknown. It is believed to be secondary to sequestration or trapping of platelets and proteins into the tumor. These tumors are made up of abnormal endothelial cells (spindle cells) and abnormal lymphatic tissue. It is unclear why the KMP occurs and if it is caused by the spindle cells or the lymphatic component. A cause for the tumor (KHE and or TA) is also unknown but possibly secondary to a change in a gene in the tissue involved (somatic gene mutation).

KMP is a rare disorder that affects males and females equally. The diagnosis is most often made during infancy. The pnenomenon occurs much less often in older children. KHE and TA tumors can occur without KMP. The reason for this is still unknown and may be secondary to a smaller size of the tumor, an older age at presentation or other clinical features.

Symptoms of the following disorders can be similar to those of Kasabach-Merritt phenomenon. Comparisons may be useful for a differential diagnosis:


常染色体显性遗传性智力障碍-颅面畸形-心脏缺陷综合征

Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome

Although researchers have been able to establish a clear syndrome with characteristic or core symptoms, much about KAT6A syndrome is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of additional genes, environmental factors, or other factors influencing the disorder have prevented physicians and researchers from developing a complete picture of associated symptoms and prognosis.

KAT6A syndrome is caused by a variation (mutation) in the KAT6A gene. This gene is also known as the MOZ or MYST3 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a variation of a gene occurs, the protein product may be faulty, inefficient, absent, or overproduced. Depending upon the functions of the protein, this can affect many organ systems of the body, including the brain.

KAT6A syndrome is believed to affect females and males in equal numbers. The exact number of people who have this disorder is unknown. According to the KAT6 Foundation, as of December 2022, there are 350 individuals known to have the disorder. Rare disorders like KAT6A syndrome often go misdiagnosed or undiagnosed, making it difficult to determine their true frequency in the general population. KAT6A syndrome is often underdiagnosed, and a 2015 report suggests that the disorder may account for as much as 1% of undiagnosed individuals with syndromic developmental delay.

Symptoms of the following disorders can be similar to those of KAT6A syndrome. Comparisons may be useful for a differential diagnosis.

A diagnosis of KAT6A syndrome is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. There are no formal diagnostic criteria established for this disorder. A diagnosis is confirmed through molecular genetic testing.


常染色体显性遗传性智力障碍-颅面畸形-心脏缺陷综合征

Variants in the KAT6B gene can lead to a broad spectrum of signs and symptoms. On either side of the spectrum are some clinical features that are associated more often with either genitopatellar syndrome (GPS) or a type of Ohdo syndrome called Say-Barber-Biesecker-Young-Simpson (SBBYS). But individuals affected by KAT6B-related disorders frequently have intermediate clinical features that are a mixture or overlap between these two syndromes. Some individuals have clinical features that do not overlap with either syndrome at all.

KAT6B-related disorders are caused by a pathogenic variant (mutation) in the KAT6B gene. This gene is also known as the MORF or MYST4 gene. Genes provide instructions for creating (encoding) proteins that play a critical role in many functions of the body. When a variant occurs, the protein that is created may be faulty, inefficient, absent, or overproduced. Depending upon the functions of the protein, this can affect many parts of the body.

KAT6B-related disorders affect females and males in equal numbers. The exact number of people who have this disorder is unknown. According to the KAT6 Foundation, as of February 2023, there are 150 individuals around the world known to have a KAT6B gene variant. Rare disorders like KAT6B-related disorders often go misdiagnosed or undiagnosed, making it difficult to determine their true frequency in the general population but it is estimated that fewer than one in a million individuals may be affected.

Clinical features of the following disorders can be similar to those of KAT6B-related disorders. Comparisons may be useful for a differential diagnosis.

A diagnosis of a KAT6B-related disorder is based upon identification of characteristic clinical features, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. No formal diagnostic criteria have been established for KAT6B-related disorders, even if clinical features cause suspicion that an individual may have GPS or SBBYS. A diagnosis can only be confirmed through molecular genetic testing.


Kawasaki disease

Kawasaki disease is an acute multisystem inflammatory disease of blood vessels (vasculitis) that most commonly affects infants and young children. The disease may be characterized by a high fever, inflammation of the mucous membranes of the mouth and throat, a reddish skin rash, and swelling of lymph nodes (lymphadenopathy). In addition, individuals with Kawasaki disease may develop inflammation of arteries that transport blood to heart muscle (coronary arteritis), associated widening or bulging (aneurysms) of the walls of affected coronary arteries, inflammation of heart muscle (myocarditis), and/or other symptoms and findings. Kawasaki disease is the primary cause of acquired heart disease in children in the United States. Although the cause of the disease is unknown, it is widely thought to be due to infection or an abnormal immune response to infection.

In many affected children, the initial symptom associated with Kawasaki disease is a high fever that typically rises and falls (remittent fever) and lasts for approximately one to two weeks without treatment.  In some cases, fever may persist for up to about three to four weeks.  Additional characteristic features include inflammation of the whites of the eyes (bilateral conjunctivitis); inflammation of mucous membranes of the mouth and throat, resulting in dry, red, cracked lips and a strawberry-red tongue; swelling of lymph nodes in the neck (cervical lymphadenopathy); redness and swelling of the hands and feet; and a reddish rash, typically affecting the trunk and often involving the groin area.  By about the second or third week, skin tissue may peel (desquamate) from the tips of the fingers and toes and may progress to involve the hands and feet.

Although the exact cause of Kawasaki disease is not known, evidence indicates an infection or an inappropriate immune response to infection.  However, despite much research in this area, a specific infectious cause has not been identified.

Kawasaki disease most frequently affects children five years of age or younger. In extremely rare cases, Kawasaki disease may occur during adolescence or adulthood. First reported in Japanese children in the 1960s, the disease is now recognized worldwide and occurs in individuals in all racial and ethnic groups. However, Kawasaki disease appears to affect Asian children most frequently. Estimates indicate that at least 3,000 cases of Kawasaki disease are diagnosed each year in the United States.  Males appear to be affected more frequently than females by a ratio of approximately 1.5 to 1.

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

Measles is a highly contagious viral disease occurring primarily in children.  Symptoms may include fever, cough, sore throat, runny nose, redness of the eyes (conjunctivitis), and increased sensitivity to light (photophobia).  Small red spots with bluish or whitish centers may appear on the inner cheeks (Koplik’s spots).  In addition, a characteristic red skin rash develops.


KBG syndrome

short stature, facial/skeletal anomalies-retardation-macrodontia

KBG syndrome (KBGS) is a rare genetic disorder characterized by large front teeth (macrodontia), characteristic facial features, short to normal stature, developmental delay or intellectual disability (the level of intellectual disability is usually mild, and there are also people with KBGS who have a normal development). Behavioral issues are common. People with KBGS can have skeletal abnormalities (such as short fingers, delayed closure of the fontanelle or scoliosis), hearing loss and feeding difficulties (particularly in infancy), and some have epilepsy (seizures) or brain malformations.  The specific symptoms may vary from one person to another. KBG syndrome is caused by a change (variant or mutation) in the ANKRD11 gene or a loss of genetic material (microdeletion) on chromosome 16q that involves the ANKRD11 gene. Variants of this gene can occur spontaneously with no family history or be inherited in an autosomal dominant manner. KBG syndrome is named after the initials of the last names of the first three families identified with this disorder in the medical literature in 1975.

Children with KBG syndrome may display characteristic physical abnormalities of the head and face (craniofacial dysmorphism). The shape of the skull can be abnormal, with a flat back of the head (brachycephaly). Characteristic facial features may include eyes that appear widely spaced apart (hypertelorism) or crossed (strabismus); wide, bushy eyebrows; thin, bow-shaped lips; prominent ears; and/or a triangularly shaped face. There is typically a full tip of the nose with upturned nostrils. Characteristic features may also include large teeth (macrodontia). Macrodontia is particularly common in KBG syndrome and often affects the two upper middle teeth (upper central incisors) and sometimes other teeth as well. Affected individuals may also have jagged, crowded or misaligned teeth and/or unusually short, flattened, supporting bones or sockets of the jaw (mandible) that house the teeth (alveolar ridges). Microcephaly has been described in some children. Microcephaly is a condition in which the circumference of the head is smaller than would be otherwise expected based on age and gender. However, most children with KBG syndrome have a normal head size.

KBG syndrome is caused by either an alteration (variant or mutation) in the ANKRD11 gene or a loss of genetic material from chromosome 16q that includes the ANKRD11 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 protein, this can affect many organ systems of the body.

KBG syndrome is a rare disorder that affects males and females. Currently, more than 150 cases have been reported in the medical literature. The actual number of patients worldwide is much higher. The disorder can go undiagnosed or misdiagnosed, making it difficult to determine the true frequency of KBG syndrome in the general population.

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

Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that is apparent at birth (congenital). Associated symptoms and findings typically include delays in physical development before and after birth (prenatal and postnatal growth delay); characteristic differences of the head and facial (craniofacial) area, resulting in a distinctive facial appearance; malformations of the hands and arms (upper limbs); and mild to severe intellectual disability. Many infants and children with the disorder have an unusually small, short head (microbrachycephaly); a prominent vertical groove between the upper lip and nose (philtrum); a depressed nasal bridge; upturned nostrils (anteverted nares); and a protruding upper jaw (maxillary prognathism) with small chin (micrognathia). Additional characteristic facial abnormalities may include thin, downturned lips; low-set ears; arched, well-defined eyebrows that grow together across the base of the nose (synophrys); an unusually low hairline on the forehead and the back of the neck; and curly, unusually long eyelashes. Affected individuals may also have distinctive malformations of the limbs, such as unusually small hands and feet, inward deviation (clinodactyly) of the fifth fingers, and webbing (syndactyly) of certain toes. Less commonly, there may be absence of the forearms, hands, and fingers. Infants with CdLS may also have feeding and breathing difficulties; an increased susceptibility to respiratory infections; a low-pitched growling cry and low voice; heart defects; delayed skeletal maturation; hearing loss; or other physical abnormalities. The range and severity of associated symptoms and findings may be extremely variable from person to person. (For more information, choose Cornelia de Lange as your search term in the Rare Disease Database).

Treatment is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, orthopedists, orthopedic surgeons, (pediatric) neurologists, physical therapists, speech therapists, orthodontists or dentists and other healthcare professionals may need to plan an affected child’s treatment systematically and comprehensively.


KCNK9 Imprinting Syndrome

Although researchers have been able to establish a clear syndrome with characteristic or core symptoms, much about the disorder is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and other factors prevent physicians from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below or may have symptoms that are not discussed. Every case is unique and the disorder can be different in one child when compared to another.

KCNK9 imprinting syndrome is caused by an alteration in the maternal copy of the KCNK9 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain.

KCNK9 imprinting syndrome is an extremely rare disorder that has been described in only several families worldwide. The incidence and prevalence of the disorder is unknown. It is likely that people with this disorder go undiagnosed or misdiagnosed, making it difficult to determine the true frequency of KCNK9 imprinting syndrome in the general population.

A diagnosis of KCNK9 imprinting syndrome is almost always made through molecular testing and confirmed by identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation with specialized tests to rule out other causes of congenital hypotonia. Molecular genetic testing looks for changes (mutations) in the KCNK9 gene known to cause the disorder, but is available only as a diagnostic service at specialized laboratories. Most cases are diagnosed by whole exome sequencing, when a specific amino acid change (p.G236R) is detected in the KCNK9 gene.


KCNQ2相关的癫痫性脑病

KCNQ2 Developmental and Epileptic Encephalopathy

The gene that is altered in patients with KCNQ2-DEE is the gene for a potassium channel within the brain.

Epilepsy is estimated to affect 1 in 26 people during their lifetime with an incidence of approximately 44/100,000 people. The incidence is highest in young children and older adults with children often having the most severe types of epilepsies. The incidence of epilepsy in children under 2 years of age is estimated to be 70.1 per 100,000 based on a recent population-based study conducted in North London. In this research, severe epilepsies associated with abnormal development and EEG (epileptic encephalopathies) were identified in 22 (39%) of 57 infants and were associated with several genetic causes.

Symptoms of the following disorders can be similar to those of KCNQ2E. Comparisons may be useful for a differential diagnosis:

Epilepsy is a group of neurological disorders characterized by abnormal electrical discharges in the brain. It is characterized by loss of consciousness, convulsions, spasms, sensory confusion and disturbances in the autonomic nervous system. There are many different types of epilepsy and seizures, and the exact cause is frequently unknown. Epilepsy can also occur as part of larger genetic syndromes. Types of epilepsy or disorders associated with epilepsy include Rett syndrome, Angleman syndrome, Dravet syndrome and West syndrome. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)


Kearns Sayre Syndrome

chronic progressive external ophthalmoplegia and myopathy

Kearns-Sayre syndrome (KSS) is a rare multisystemic disorder. An important clinical symptomatic feature is the presence of droopy eyelids (ptosis) in one or both eyes. This disease is mostly characterized by three primary findings: progressive paralysis of certain eye muscles (chronic progressive external ophthalmoplegia [CPEO]); abnormal accumulation of colored (pigmented) material on the nerve-rich membrane lining the eyes (atypical retinitis pigmentosa), or pigmentary retinopathy, leading to poor night vision and progressive vision loss; and heart disease such as cardiomyopathy and/or progressive arrhythmia leading to complete heart block. Other findings may include muscle weakness, short stature, sensorineural hearing loss, endocrine issues such as diabetes mellitus and hypoparathyroidism (which can cause hypocalcemia) and/or the loss of ability to coordinate voluntary movements (ataxia) due to problems affecting part of the brain (cerebellum). In some patients, KSS may be associated with other disorders and/or conditions.

The three primary findings in KSS are progressive paralysis of certain eye muscles including the eyelid (ptosis) leading to chronic progressive external ophthalmoplegia (CPEO), pigmentary retinopathy, and heart disease such as an arrhythmia leading to complete heart block or cardiomyopathy. Symptoms of this disorder are usually apparent before the age of 20 years.

The exact cause of KSS is established in most patients. Most cases appear to occur as the result of a new spontaneous (de novo) deletion of a large amount (typically ~25%) of genetic material found in the DNA of mitochondria (mtDNA). Mitochondria, which are found by the hundreds in the cells of the body, particularly in muscle and nerve tissue, carry the blueprints for regulating energy production. As opposed to the genetic instructions of cellular chromosomes (nuclear DNA), which are found within the nucleus of each cell, multiple copies of mitochondrial DNA are found outside of the nucleus of the cell and within the mitochondria.

KSS is a mitochondrial disorder that affects males and females in equal numbers. Onset is typically before the age of 20; however, symptoms may appear during infancy or adulthood. Eye abnormalities and developmental delays are often observed before the age of five.

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

MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), is also in the family of disorders known as mitochondrial encephalomyopathies. Mitochondrial encephalomyopathies are disorders in which a defect in the genetic material arises from a part of the cell structure that regulates energy production (mitochondria), causing the brain and muscles to function improperly (encephalomyopathies). The distinguishing feature in MELAS syndrome is the recurrence of stroke-like symptoms. Episodes of sudden headaches with vomiting and seizures may begin any time between the ages of five to 40 years. Muscular weakness on one side of the body (hemiparesis), blindness due to lesions in the area of the brain that regulates vision (cortical blindness), and/or impaired vision or blindness in one half of the visual field (hemianopsia) may also occur. In addition, individuals with MELAS syndrome may also exhibit an abnormal accumulation of lactic acid in the blood (lactic acidosis), progressive dementia, deafness, diabetes, and short stature. (For more information on this disorder, choose MELAS as your search term in the Rare Disease Database.)


Kennedy disease

Affected individuals begin to develop neurological symptoms between 20 to 50 years of age. These early symptoms include:

Kennedy disease is caused by a change (variant or mutation) in the AR gene that encodes for a protein known as the androgen receptor on the X chromosome. The instructions within every gene consist of different arrangements of four basic chemicals (nucleotide bases) called adenine (A), cytosine (C), guanine (G), and thymine (T). Individuals with the disease have an abnormal section in the AR gene, which is due to an excessive number of CAG trinucleotide repetitions in the DNA sequence. An unaffected individual has 10-35 CAG repeats in the AR gene while a person with Kennedy disease has more than 36 CAG repeats in the gene.

Kennedy disease affects approximately 1/200,000 people worldwide and is very rare in females. Kennedy disease has been diagnosed in the USA, Europe, Asia, South America and Australia. The Japanese population appears to have a very high prevalence of Kennedy Disease because of a founder effect.

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

Adrenoleukodystrophy (ALD) is one of many different leukodystrophies. The adolescent or adult-onset form of the disorder is called adrenomyeloneuropathy (AMN), and symptoms of this form of ALD may be similar to those of Kennedy disease. Symptoms typically appear between the ages of 21 and 35. They may include progressive leg stiffness, spastic partial paralysis of the lower extremities and ataxia (clumsiness in walking). Decreased function of the sex glands may be present. Adult-onset ALD progresses slowly; however, it can ultimately result in deterioration of brain function. (For more information on this disorder, choose adrenoleukodystrophy as your search term in the Rare Disease Database.)


Kenny-Caffey syndrome

dwarfism, cortical thickening of tubular bones & transient hypocalcemia

Kenny-Caffey syndrome type 2 (KCS2) is an extremely rare hereditary skeletal disorder characterized by thickening of the long bones, thin marrow cavities in the bones (medullary stenosis), and abnormalities affecting the head and eyes. Most cases are obvious at birth (congenital). The primary outcome of KCS2 is short stature. Intelligence is usually normal. Individuals with KCS may also have recurrent episodes of low levels of calcium in the blood stream (hypocalcemia) that is caused by insufficient production of parathyroid hormones (hypoparathyroidism). In most cases, KCS2 is an autosomal dominant genetic disorder.

KSC2 is present at birth (congenital) and low birth weight may be one of the first symptoms. This extremely rare genetic disorder is characterized by abnormalities affecting the skeleton, the head, and the eyes. Recurrent episodes of unusually low levels of calcium (hypocalcemia) in the blood are common. Most affected individuals, exhibit short stature of adult height ranging from 48 to 59 inches.  Intelligence is usually normal.

In most cases, KCS2 is an autosomal dominant genetic disorder.  Genetic diseases are determined by two genes, one received from the father and one from the mother.

KCS2 is an extremely rare skeletal disorder that affects males and females in equal numbers. Fewer than 60 cases have been reported in the medical literature. Onset of hypocalcemia is usually within two to three months of life; the hypocalcemia is not permanent (transient). In an adult, episodes of hypocalcemia may be due to stress or follow surgery or illness. KCS2 was first described in the medical literature in 1966.

Symptoms of the following disorders can be similar to those of Kenny-Caffey syndrome type 2. Comparisons may be useful for a differential diagnosis:

The diagnosis of KCS2 may be confirmed by x-ray studies of the skeleton that reveal distinctive thickening of the outer layers (cortexes) of long bones along with unusually thin marrow cavities. Blood tests can detect episodes of low levels of calcium in the blood (hypocalcemia).


Keratitis Ichthyosis Deafness Syndrome

角膜炎-鱼鳞病-耳聋综合征

Ichthyosiform Erythroderma, Corneal Involvement, and Deafness Syndrome

Keratitis ichthyosis deafness (KID) syndrome is a rare, genetic, multi-system disorder. It is characterized by defects of the surface of the corneas (keratitis), red, rough thickened plaques of skin (erythrokeratoderma) and sensorineural deafness or severe hearing impairment. The skin on the palms of the hands and soles of the feet and the nails may be affected. KID syndrome belongs to a group of skin disorders marked by dry, scaly skin known as the ichthyoses. KID syndrome is inherited as an autosomal dominant trait.

KID syndrome is present at birth.  Nearly all cases have skin involvement, which includes red, rough, thickened plaques that are sometimes scaling, as well as sensorineural deafness or severe hearing impairment.

KID syndrome is a genetic disorder and can be transmitted from a parent to a child in an autosomal dominant fashion. That means that each individual affected with the disease will have one abnormal gene for the disease and one normal gene. When, by chance, the abnormal gene copy is passed on to the offspring, the child will be affected. When the normal gene copy is transmitted, the child will be unaffected. The risk for an adult with KID syndrome to have an affected child is 50% for each pregnancy. Nevertheless, approximately nine out of ten patients carry a new, spontaneously occurring mutation that is not present in either parent.

KID syndrome appears to affect females slightly more often than males. The disorder is very rare with fewer than 100 cases reported in the medical literature. Collectively, the ichthyoses affect more than 1,000,000 people in the United States.

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

Ichthyoses or disorders of cornification are general terms describing a group of scaly skin disorders.  They are characterized by an abnormal accumulation of large amounts of dead skin cells (squames) in the top layer of the skin.  The conversion of an abnormally large number of epidermal cells into squamous cells is thought to be caused by a defect in the metabolism of the skin cells known as corneocytes or the fat-rich matrix around these cells.  These cells can be thought of as bricks, while the matrix would be the mortar holding these cells together.  (See Ichthyosis in the Rare Disease Database.)

Individuals with KID syndrome usually require multidisciplinary treatment due to the involvement of several organ systems and the potential impairment of hearing, speech, and sight.


Keratoconus

Keratoconus is an eye (ocular) disorder characterized by progressive thinning and changes in the shape of the cornea. The cornea is the thin, clear outer layer of the eye and is normally dome-shaped. Slowly progressive thinning of the cornea causes a cone-shaped bulge to develop towards the center of the cornea in the areas of greatest thinning. Affected individuals develop blurry or distorted vision, sensitivity to light (photophobia) and additional vision problems. Keratoconus often begins at puberty and most often is seen in teenagers or young adults. The specific underlying cause is not fully understood and most likely the condition results from the interaction of multiple factors including genetic and environmental ones. One factor known to contribute to progression of keratoconus is eye rubbing. In some cases, keratoconus may occur as part of a larger disorder. Keratoconus is treated with glasses or contact lenses early in the condition. A small number of individuals may require surgery.

The corneas in both eyes are usually affected (bilateral), although the progression and severity of the condition in each eye may differ (asymmetric development), which means one eye may be notably worse than the other. Symptoms usually become apparent during adolescence or young adulthood (i.e., late teens through early 20s). Keratoconus may become progressively worse for 10 to 20 years before slowing. Older adults typically do not have worsening of keratoconus. Because of the progressive nature of the disorder, affected individuals may have to change glasses frequently.

The specific underlying mechanism(s) responsible for keratoconus are not fully understood. Most cases appear to occur randomly for unknown reasons (sporadically). However, a positive family history of keratoconus has been established in some cases. Most researchers believe that multiple, complex factors are required for the development of keratoconus including both genetic and environmental factors.

Keratoconus affects both men and women and all ethnic groups worldwide. The disorder tends to develop most often among adolescents at or around puberty or during the late teen-age years. Males, African Americans and Latinos have a greater risk of development keratoconus, while females, Asian-Americans, and people with diabetes appear to have a lower risk.

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

There are a variety of conditions that can resemble keratoconus including abnormal thinning and steepening of the outer (peripheral) edges of the cornea (pellucid marginal degeneration); thinning of the cornea and an abnormal globe-shaped (globular) or spherical form to the cornea (keratoglobus); chronic non-ulcerative infiltration in the deep layers of the cornea of the eye (interstitial keratitis); and the corneal dystrophies, a group of genetic, often progressive, eye disorders in which abnormal material often accumulates in the cornea.


Keratolytic winter erythema

KWE is characterized by the cyclical patchy redness and thickening of the skin of the palms and soles, followed by the appearance dry blisters which subsequently peel in an expanding pattern. The shedding skin has a thickish peel. The revealed surface skin appears glazed. These signs first appear during infancy or childhood and the disorder usually improves with age. The condition may be worsened by cold weather or episodes of fever.  Secondary infection may complicate the condition. In some patients, slowly enlarging circular red patches may develop, usually on the extremities. These slowly expand and have a trailing edge of peeling.  Other frequently encountered associated symptoms include itching, excessive sweating (hyperhidrosis or palmoplantar sweating) and a strong unpleasant odor.

KWE is inherited and follows an autosomal mode of inheritance with males and females equally affected. It has been found to be associated with a duplication of an area of a chromosome that included an element known as an enhancer.  This ‘switches on’ a nearby gene or genes. One of these appears to be the gene CTSB which is has been shown to be overexpressed. The protein produced by this gene is cathepsin B. This is an enzyme that plays an important role in proteolysis (breakdown of proteins) causing a major disruption to the epidermal cell’s normal growth and development. These damaged cells fail to mature properly and are pushed outwards, still retaining their nuclei and this forms the peel.

In South Africa, families with KWE are scattered throughout the country and some families have emigrated to the UK and to other countries.  The condition is much more common in South Africa owing to the founder effect. It affects families of both the white population and those of mixed racial descent. The patients in Germany, Denmark, Norway and the USA do not share the same ancestry.

Conditions causing peeling of the palms and soles include both acquired conditions as well as other familial conditions. In some circumstances, palmoplantar peeling may be an acute phenomenon related to infections or drug reactions and such transient conditions will not be considered further.

The diagnosis of KWE is based on the clinical findings of cyclical peeling of skin on the palms and soles and a family history of this condition. In most patients, skin biopsies are not required for the diagnosis. Genetic testing is limited to research laboratories.


Keratosis Follicularis Spinulosa Decalvans

Keratosis follicularis spinulosa decalvans (KFSD) is a rare, inherited, skin disorder. KFSD is characterized by hardening of the skin (keratosis) on several parts of the body. Most frequently, the face, neck, and forearms are involved. The thickening of the skin is accompanied by the loss of eyebrows, eyelashes and beard. Baldness (alopecia) usually occurs. People with KFSD may have reduced tolerance to bright light (photophobia), inflammation of the eyelids (blepharitis), and inflammation of the outer membrane of the eyeball and the inner eyelid (conjunctivitis, also known as pink eye). Some have abnormal accumulation of material in the clear outer layer of the eye (corneal dystrophy), which may cause loss of vision or blurred vision. Some may also have poor fingernail formation.

KFSD is a type of ichthyoses, a group of inherited disorders of the skin in which the skin tends to be thick and rough and has a scaly appearance. Hardening of the skin around the hair follicles leads to scarring and baldness. This condition begins in infancy, initially appearing on the face and neck, and then progresses to the chest, back, abdomen, arms and legs. Hair loss of the eyebrows and scalp caused by the scarring become evident in childhood and progress until teenage years.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

KFSD is a rare disorder affecting males more severely than females. Because some people with KFSD may go unrecognized or undiagnosed, determining the true frequency of these disorders in the general population is difficult. KFSD is estimated to affect about less than 1 in 1,000, 000 people in the general population.

Symptoms of the following disorders may be similar to those of keratosis follicularis spinulosa decalvans. Comparisons can be useful for a differential diagnosis:

Tinea capitis (scalp ringworm) is a fungal infection of the scalp caused by different species of fungus. It is not inherited. Most cases occur between the ages of 3-7 years. It presents as numerous scaly macules and patches of broken hairs and alopecia on the scalp. More severe forms are associated with inflammatory papules, pustules, and plaques as well as systemic symptoms such as fever and malaise.


Darier disease

Keratosis follicularis, also known as Darier disease, is a rare, genetic skin disorder. Affected individuals develop skin lesions that consist of thickened, rough bumps (papules) or plaques that may also be greasy or have a brown or yellow crust. These hardened, scaly lesions may gradually grow bigger or spread. The nails and mucous membranes are also affected in most patients. Individuals may have periods of time when signs improve (remission), but the lesions usually recur (relapse). The specific problems vary from one individual to another. Keratosis follicularis is inherited in an autosomal dominant pattern.

The symptoms of keratosis follicularis usually become apparent during the teen-age years often around puberty. Symptoms may develop in younger or older individuals, but rarely develop after the third or fourth decade of life. The severity of the disorder and the specific symptoms that develop vary, even among individuals within the same family.

Keratosis follicularis is a genetic disorder that occurs randomly as the result of a spontaneous genetic change (i.e., new pathogenic variant or mutation) or the variant is inherited in an autosomal dominant pattern.

Keratosis follicularis affects males and females in equal numbers. It is estimated to occur in 1 in 36,000 to 100,000 individuals in the general population. The disorder usually becomes apparent during the second decade in life but has developed in individuals as young 4 and older than 70. Keratosis follicularis was first described in the medical literature in 1889.

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

A diagnosis of keratosis follicularis is made based upon a thorough clinical evaluation, a detailed history from the affected individual including the family history, identification of characteristic findings and microscopic examination (biopsy) of affected skin tissue. A biopsy may reveal abnormal formation of keratin tissue (keratinization) and failure of cell-to-cell adhesion (acantholysis).


Bilirubin encephalopathy

Kernicterus is a rare neurological disorder characterized by excessive levels of bilirubin in the blood (hyperbilirubinemia) during infancy. Bilirubin is an orange-yellow bile pigment that is a byproduct of the natural breakdown of hemoglobin in red blood cells (hemolysis). Toxic levels of bilirubin may accumulate in the brain, potentially resulting in a variety of symptoms and physical findings. These symptoms may include lack of energy (lethargy), poor feeding habits, fever, and vomiting. Affected infants may also experience the absence of certain reflexes (e.g., Moro reflex, etc.); mild to severe muscle spasms including those in which the head and heels are bent backward and the body bows forward (opisthotonus); and/or uncontrolled involuntary muscle movements (spasticity). In some cases, infants with kernicterus may develop life-threatening complications.

In some cases, symptoms and physical findings of kernicterus appear two to five days after birth.  Within the first few days of life, affected infants develop abnormally high levels of bilirubin in the blood (hyperbilirubinemia) and persistent yellowing of the skin, mucous membranes, and whites of the eyes (jaundice).  Toxic levels of bilirubin may accumulate in certain areas of the brain (i.e., the basal ganglia and the brainstem), potentially resulting in a variety of symptoms and physical findings that, in some cases, may cause life-threatening complications.

Some cases of kernicterus occur randomly, for no apparent reason (sporadically).  According to the medical literature, excess levels of bilirubin (hyperbilirubinemia) alone is not sufficient to produce kernicterus.  Potential causes may include Rh disease and/or unknown factors.

Kernicterus is a rare neurological disorder that affects newborn infants of both sexes in equal numbers.  Kernicterus occurs more often in premature infants than full-term infants.

Kernicterus may be suspected within the first days of life. The diagnosis may be based upon a thorough clinical evaluation and identification of characteristic physical findings (e.g., jaundice, abnormal cry, loss of Moro reflex, etc.). In most cases, persistent yellowing of the skin, mucous membranes, and whites of the eyes (jaundice) is apparent within the first few days of life.


Kienbock disease

Kienböck Disease is an acquired bone disorder. Abnormalities of the lunate bone in the wrist develops following an injury or inflammation. Recurrent pain and stiffness occur in conjunction with thickening, swelling and tenderness in soft tissue overlying the lunate bone. The range of motion in the wrist may become limited.

Kienböck Disease is characterized by degenerative changes in the lunate bone of the wrist.  Softening, deterioration, fragmentation or compression of the affected bone can occur.  These changes may produce pain, swelling, tenderness, thickening and/or stiffness in the overlying tissues of the wrist.  The range of motion may become restricted.  Many individuals with Kienböck Disease have a shorter ulna than radius (negative ulnar variance).  Healing occurs through formation of new bone in some cases.

The exact cause of Kienböck Disease is not known.  However, it is believed to be caused by inflammation or injury of the wrist.

Kienböck Disease usually begins during childhood and seems to affect females more often than males.

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

Carpal Tunnel Syndrome is a condition caused by compression of peripheral nerves in the wrist, affecting one or both hands.  It is characterized by a sensation of numbness, tingling, burning and/or pain in the hand and wrist. Persons affected by this disorder may be awakened at night with the feeling that the hand has gone to sleep.  Various other diseases may occur in conjunction with this condition.  With timely treatment, the prognosis in most cases is favorable.  (For more information on this disorder, please choose Carpal Tunnel as your search term online.)


Kikuchi-Fujimoto disease

histiocytic necrotizing lymphadenitis (HNL)

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenopathy, is a rare, benign (noncancerous, nonmalignant) disorder of the lymph nodes, predominantly of young adults and school aged children. While slightly more common in females, it is also seen in males. This disorder presents with similar signs and symptoms as lymphoma, including enlarged lymph nodes (lymphadenopathy) The exact cause is not known. KFD shows up as painful swelling of lymph nodes, often in the neck, along with general symptoms like fever and fatigue.

KFD is a rare nonmalignant disorder that affects the lymph nodes. Lymph nodes are present throughout the body as small oval or kidney bean shaped structures that filter lymph fluid, fight infection and form white blood cells and blood plasma cells. Enlarged and painful lymph nodes are commonly in the neck region, but supraclavicular, axillary, thoracic, intraparotid, abdominal and pelvic lymph nodes may also be involved.

The exact cause of KFD is not known (idiopathic). It is thought that an abnormal immune response, possibly influenced by viral infection or genetic factors, may play a role. It is thought to be related to viral infections like HIV, HSV, VZV and EBV, as well as autoimmune conditions such as lupus, sarcoidosis, lymphoma and Sjogren’s syndrome. Another theory is that KFD is a self-limited autoimmune condition. Autoimmune disorders are caused when the body’s natural defenses against foreign or invading organisms begin to attack healthy tissue for unknown reasons.

KFD, first identified in Japan in 1972, is extremely rare.

KFD may resemble other conditions that cause swollen lymph nodes such as lymphoma, tuberculosis, systemic lupus erythematosus (SLE) and infectious mononucleosis. Whether KFD is present at the start of SLE, coexists with SLE, or evolves into SLE depends on the patient’s condition. Symptoms of the following disorders can be similar to those of KFD. Comparisons may be valid for a differential diagnosis:

Burkitt’s lymphoma is a cancer of the lymphatic system that affects the lymph nodes as well as other areas of the body. Tumors may occur in the kidneys, sex glands, jaw, bone marrow, central nervous system and lymph nodes. Burkitt’s lymphoma may be infectious. This disorder often occurs in children living in Central Africa and is associated with the Epstein-Barr virus.

Treatment of KFD is symptomatic and supportive. Usually, the disorder resolves spontaneously within a few weeks or months. Analgesics-antipyretics and nonsteroidal anti-inflammatory (NSAIDs) may be used to treat pain, tenderness and lymphadenopathy-related fever. In extremely rare cases, KFD may recur.


Kleefstra Syndrome

Kleefstra syndrome has a wide range of symptoms that include physical, developmental and behavioral characteristics. While some physical features are apparent from birth (congenital), other symptoms, particularly behavioral, often develop during early childhood.

Kleefstra syndrome is a genetic condition caused by changes in a specific region of chromosome 9, known as 9q34.3. The genetic changes that lead to Kleefstra syndrome can take different forms, including deletions (missing pieces) of the chromosome or pathogenic variants (previously known as mutations) within a specific gene called EHMT1.

Kleefstra Syndrome affects both males and females equally. It occurs in people from all ancestral backgrounds. How often it occurs is not well understood. Many people with Kleefstra syndrome may be undiagnosed, making it challenging to accurately gauge the frequency of the disorder in the general population.

Symptoms of the following disorders can be similar to those of Kleefstra syndrome.

Kleefstra Syndrome may first be suspected based on characteristic features of the condition and tests done in a clinical evaluation. Often, a person with Kleefstra syndrome will be the only person with the condition in their family history. Molecular genetic testing that identifies the characteristic deletion in chromosome 9 or identifies a variant in the EHMT1 gene can confirm the diagnosis. Molecular genetic testing for the parents might also be recommended. A genetic counselor can explain what type of testing is most appropriate for the child and family.


Kleine-Levin Syndrome

Kleine-Levin syndrome is a rare disorder characterized by the need for excessive amounts of sleep (hypersomnolence), (i.e., up to 20 hours a day); excessive food intake (compulsive hyperphagia); and behavioral changes such as an abnormally uninhibited sexual drive. The disorder primarily affects adolescent males. When awake, affected individuals may exhibit irritability, lack of energy (lethargy), and/or lack of emotions (apathy). They may also appear confused (disoriented) and experience hallucinations. Symptoms of Kleine-Levin syndrome are cyclical. An affected individual may go for weeks or months without experiencing symptoms. When present, symptoms may persist for days to weeks. In some cases, the symptoms associated with Kleine-Levin syndrome eventually disappear with advancing age. However, episodes may recur later during life.

Kleine-Levin syndrome is an extremely rare disorder characterized by the need for excessive amounts of sleep (hypersomnolence), excessive eating (compulsive hyperphagia), and behavioral abnormalities.

The exact cause of Kleine-Levin syndrome is unknown. It is speculated that symptoms may develop due to malfunction or damage to the portion of the brain that helps to regulate functions such as sleep, appetite, and body temperature (hypothalamus). As with most diseases with no known cause, some researchers have speculated that, in some cases, symptoms may develop as a result of a head injury or an infectious disease affecting the hypothalamus; however, this is unproven.

Kleine-Levin syndrome is a rare sleep disorder that primarily affects adolescent males, usually around the age of 16 years. However, there have been cases involving females and older men. Males appear to be affected three times as often as females (M3:F1). On average, women had a longer disease course than men.

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

Kleine-Levin syndrome may be suspected based upon a thorough clinical evaluation and a detailed patient history. Kleine-Levin syndrome may be confirmed based upon excessive sleep requirements (hypersomnolence); the desire to eat all available food (compulsive hyperphagia); and hypersexuality. Certain medical tests may be performed to rule out other conditions such as epilepsy, brain lesions, meningitis or encephalitis.


Klippel-Feil Syndrome

KFS is a rare skeletal condition in which there is abnormal union and fusion of two or more vertebrae within the neck. The spinal column or backbone is made up of 33 irregularly shaped bones known as vertebrae. These bones are divided into different categories. The first seven vertebrae, beginning at the base of the skull, are known as the cervical vertebrae. KFS primarily affects the cervical vertebrae.

In most individuals with KFS, the condition appears to occur randomly for unknown reasons (sporadically). However, in other cases, familial patterns have been reported that indicate autosomal dominant or autosomal recessive inheritance. Most likely, KFS is multifactorial, which means that several different factors including genetic factors all play some causative role. In addition, different genetic changes can cause KFS (genetic heterogeneity) in different people.

The exact incidence of the disorder is unknown, although reports estimate that the condition occurs in approximately one in 42,000-50,000 live births. KFS affects females more frequently than males. More specifically, approximately 65 percent of affected individuals are female. According to reports in the medical literature, KFS type II appears to be the most common form of the condition.

Symptoms of the following disorder may be similar to those of KFS. Comparisons may be useful for a differential diagnosis:

Multiple synostosis (SYNS) is also associated with the fusion of cervical vertebrae. Multiple synostosis 4 (SYNS4) is caused by variants in the GDF6 gene. SYSN4 is very difficult to distinguish from KFS because SYSN4 is also congenital and progressive with vertebral fusion from a very early age. Some people were wrongly diagnosed with KFS but in fact have SYSN4.


Klippel-Trenaunay Syndrome

KTS is caused by a change (variant or mutation) in the PIK3CA gene. This mutation does not occur in the germ cells (egg and sperm) but only in the body cells after fertilization. Therefore, KTS is not an inherited condition and is not passed on in a family.

Klippel-Trenaunay syndrome is a rare disorder affecting males and females in equal numbers. The disorder occurs worldwide.

KTS can be confused with other combined vascular disorders.

KTS is diagnosed based on physical signs and symptoms. Computed axial tomography (CAT) and magnetic resonance imaging (MRI) scans, and color doppler studies may be useful in determining the extent of the condition and how best to manage it.


Kluver-Bucy Syndrome

Kluver-Bucy syndrome is a very rare cerebral neurological disorder associated with damage to both temporal lobes resulting in abnormalities in memory, social and sexual functioning and unusual (idiosyncratic) behaviors.

Major symptoms may include excessive oral tendencies with hyperorality (an urge to put inappropriate objects into the mouth), hypermetamorophosis (a need to touch everything), compulsive eating, hypersexuality (extreme sexual behavior), visual agnosia (difficulty identifying objects), docility or plasticity (easily influenced), lack of normal fear, indifference, memory loss and other emotional changes. When associated with temporal frontal dementia, seizures or traumatic brain injury, there may be additional symptoms.

Kluver-Bucy syndrome is the result of bilateral damage to the temporal lobes of the brain. This may be the result of trauma to the brain, tumors, degenerative brain diseases or some brain infections, most commonly herpes simplex encephalitis (a viral brain infection).

Kluver-Bucy syndrome is a very rare disease that affects males and females equally.

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

Frontotemporal degeneration is a rare progressive neurological disease initially predominately affecting the frontal and temporal lobes of the brain. It is characterized by an initial predominance of changes in behavior and personality without memory changes. However, in later stages there is loss of motor control as well as confusion and severe dementia. (For more information on this disorder, choose frontotemporal degeneration as your search term in the Rare Disease Database.)

Treatment of Kluver-Bucy syndrome is supportive and psychotropic medications may be effective for some of the associated symptoms.


Kniest Dysplasia

Kniest dysplasia is one of several forms of dwarfism that is caused by a change (mutation) in a gene known as COL2A1. This gene is involved in the production of a particular protein that forms type 2 collagen, which is essential for the normal development of bones and other connective tissue. Changes in the composition of type 2 collagen lead to abnormal skeletal growth and, thus, to a variety of dwarfing conditions known as skeletal dysplasias.

People with Kniest dysplasia are known to have an unusually short stature; short, deformed arms and legs; a chest that is barrel-shaped and abnormally short; and a relatively long trunk.  Later in life, short trunk dwarfism develops due to curvature of the spine and enlargement of the joints.

Kniest dysplasia is the result of a change (mutation) in the gene known as COL2A1, which produces (codes for) the protein that forms collagen type 2.  This gene has been mapped to the following gene map locus: 12q13.11-q13.20.  The disorder is transmitted from parent to child as an autosomal dominant trait.  In some instances, the mutation appears to be spontaneous, occurring for no apparent reason.

Kniest Syndrome is a rare disorder that affects males and females in equal numbers.

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

Hypochondrogenesis (underdevelopment or lack of development of cartilage) is characterized by short-limb dwarfism, swelling of the body and face, widely spaced eyes (hypertelorism), a flat face and cleft palate.  Respiratory distress may develop, due to the small rib cage, and is a significant concern.  This disorder is an autosomal dominant trait.  The mutation may be spontaneous in many cases.


Osteochondrosis of the tarsal bone

Kohler's Disease of the tarsal navicular

Kohler disease is a rare bone disorder of the foot in children that may be the result of stress-related compression at a critical time during the period of growth. It is characterized by limping caused by pain and swelling in the foot. It most often occurs in children between the ages 3-7, and affects males five times more often than females. Usually, just one foot is affected so children typically walk on the side portion of the foot.

Kohler disease is a rare bone disorder characterized by a painful swollen foot. The foot is especially tender along the length of the arch. It may include redness of the affected area. Putting weight on the foot or walking is difficult, causing further discomfort and a limp. For reasons that are not understood, the flow of blood to one of the bones in the foot (navicular bone) is interrupted, resulting in progressive degeneration of that bone. In a relatively short time, however, the bone heals itself.

The exact cause of Kohler disease is unknown.

Kohler disease is a rare bone disorder of the foot that affects males more often than females. The disorder strikes children between the ages of 1 and 10 years with a peak occurring at ages 3 to 7 years. The center of bone growth that is affected in Kohler disease develops in young girls about one year before it appears in young boys. Nevertheless, the disorder is five times more prevalent in boys than girls.

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

Freiberg Disease is a rare bone disorder characterized by a pain in the area of the second or third metatarsals (long bones of the foot). Putting weight on the foot or walking can cause further discomfort and lead to a limp. This condition is usually diagnosed during adolescence or in the twenties.


17q21.31 microdeletion syndrome

Koolen-de Vries syndrome (KdVS) is a rare genetic disorder with an estimated prevalence of about 1 in 30,000 people. Frequent features in individuals with this condition include feeding problems in infancy, muscle weakness (hypotonia) in young children, developmental problems, language/speech delay, learning disabilities and mild to moderate intellectual disability, epilepsy (in about 1 in 3 persons), characteristic facial features, farsightedness, hearing impairment, flexible joints, flat feet and curvature of the spine and/or congenital abnormalities.

KdVS is associated with a broad spectrum of symptoms that vary greatly from person to person. Some individuals are more affected than others and an individual with KdVS will not have all the symptoms mentioned in this section. For instance, most will learn to speak at a later age, while some may not speak at all.

KdVS is caused by a deletion of a small part of chromosome 17 or by a change (pathogenic variant) in the KANSL1 gene. Chromosomes are the carriers of the genetic information and are important for directing and regulating all processes in the body. The part of chromosome 17 that is missing in many people with KdVS is denoted by q21.31. The missing portion of the hereditary material is called a deletion. Because this small deletion is not visible with older techniques, the syndrome was first known as a 17q21.31 microdeletion. Until 2012, KdVS was called the 17q21.31 microdeletion syndrome, but in 2012 it was discovered that variants in the KANSL1 gene (one of the genes in the 17q21.31 region) can lead to the KdVS. This is the reason the condition was renamed. There is no relationship between the size of the deletion and the degree of symptoms. Furthermore, there is no clinical difference between persons with a 17q21.31 deletion and a KANSL1 pathogenic variant.

The prevalence of Koolen-de Vries syndrome is unknown. The estimated prevalence of the 17q21.31 deletion is 1 in 30,000 individuals. Preliminary data suggest that pathogenic variants in the KANSL1 gene may be as frequent as the microdeletions, but more studies are needed to determine an unbiased prevalence. Koolen-de Vries syndrome occurs with equal frequency in males and females.

There are other conditions with symptoms similar to KdVS. Conditions that might be included in a differential diagnosis include 22q11.2 deletion syndrome, Prader-Willi syndrome, fragile X syndrome, Angelman syndrome and cardiofaciocutaneous syndrome.

Koolen-de Vries syndrome can be diagnosed in an individual with the typical symptoms described above and either of the following genetic abnormalities: