1q21.1 microduplication is a chromosomal change in which a small amount of genetic material on chromosome 1 is abnormally copied (duplicated). The duplication occurs on the long (q) arm of the chromosome at a location designated q21.1. Some people with a 1q21.1 microduplication have developmental delay and intellectual disability that is typically mild to moderate. Individuals with this condition can also have features of autism spectrum disorder . These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language.

1q21.1 microduplication is a chromosomal change in which a small amount of genetic material on chromosome 1 is abnormally copied (duplicated). The duplication occurs on the long (q) arm of the chromosome at a location designated q21.1. Some people with a 1q21.1 microduplication have developmental delay and intellectual disability that is typically mild to moderate. Individuals with this condition can also have features of autism spectrum disorder. These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language.

1q21.1 duplication syndrome Other names 1q21.1 (recurrent) microduplication 1q21.1 duplication syndrome is inherited in an autosomal dominant manner Specialty Medical genetics 1q21.1 duplication syndrome or 1q21.1 (recurrent) microduplication is a rare aberration of chromosome 1 . In a common situation a human cell has one pair of identical chromosomes on chromosome 1. With the 1q21.1 duplication syndrome one chromosome of the pair is over complete, because a part of the sequence of the chromosome is duplicated twice or more. In 1q21.1, the '1' stands for chromosome 1, the 'q' stands for the long arm of the chromosome and '21.1' stands for the part of the long arm in which the duplication is situated. Next to the duplication syndrome, there is also a 1q21.1 deletion syndrome .

1q21.1 microduplication syndrome is a rare partial autosomal trisomy/tetrasomy with incomplete penetrance and variable expression characterized by macrocephaly, developmental delay, intellectual disability, psychiatric disturbances (autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, mood disorders) and mild facial dysmorphism (high forehead, hypertelorism). Other associated features include congenital heart defects, hypotonia, short stature, scoliosis.

VLDLR-associated cerebellar hypoplasia Other names Dysequilibrium syndrome , DES ; Nonprogressive cerebellar disorder with mental retardation ) VLDLR-associated cerebellar hypoplasia ( VLDLRCH ) is a rare autosomal recessive condition caused by a disruption of the VLDLR gene. [1] [2] First described as a form of cerebral palsy in the 1970s, [3] it is associated with parental consanguinity and is found in secluded communities, with a number of cases described in Hutterite families. [4] References [ edit ] ^ Boycott KM, Flavelle S, Bureau A, Glass HC, Fujiwara TM, Wirrell E, Davey K, Chudley AE, Scott JN, McLeod DR, Parboosingh JS (2005). "Homozygous deletion of the very low density lipoprotein receptor gene causes autosomal recessive cerebellar hypoplasia with cerebral gyral simplification" . Am. J. Hum. Genet . 77 (3): 477–83. doi : 10.1086/444400 . PMC 1226212 . PMID 16080122 . ^ Moheb LA, Tzschach A, Garshasbi M, Kahrizi K, Darvish H, Heshmati Y, Kordi A, Najmabadi H, Ropers HH, Kuss AW (2008). "Identification of a nonsense mutation in the very low-density lipoprotein receptor gene (VLDLR) in an Iranian family with dysequilibrium syndrome" .

Dysequilibrium syndrome (DES) is a non-progressive cerebellar disorder characterized by ataxia associated with an intellectual disability, delayed ambulation and cerebellar hypoplasia. Epidemiology To date, more than 50 individuals have been reported in the world literature. Clinical description DES is a congenital disorder characterized by nonprogressive cerebellar ataxia, associated with a moderate to profound intellectual disability and delayed ambulation. Gait can be either bipedal or quadrupedal. Additional features include hypotonia, lack of coordination, delayed motor development, seizures, dysarthria, strabismus, short stature and pes planus. Etiology Etiological subtypes of DES have been reported and include type 1 (CAMRQ1), 2 (CAMRQ2), 3 (CAMRQ3) and 4 (CAMRQ4) which are attributed to mutations in VLDLR (9p24), CA8 (8q12.1), WDR81 (17p13.3) and ATP8A2 (13q12) genes, respectively.

A number sign (#) is used with this entry because cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ1) is caused by homozygous mutation in the VLDLR gene (192977), which encodes the very low density lipoprotein receptor, on chromosome 9p24. Description This form of autosomal recessive cerebellar ataxia is characterized by congenital onset of nonprogressive cerebellar ataxia, disturbed equilibrium, and mental retardation, associated with cerebellar hypoplasia (Schurig et al., 1981; Glass et al., 2005). Genetic Heterogeneity of CAMRQ CAMRQ is a genetically heterogeneous disorder. See also CAMRQ2 (610185), caused by mutation in the WDR81 gene (614218) on chromosome 17p; CAMRQ3 (613227), caused by mutation in the CA8 gene (114815) on chromosome 8q11; and CAMRQ4 (615268), caused by mutation in the ATP8A2 gene (605870) on chromosome 13q12. Clinical Features Schurig et al. (1981) reported an autosomal recessive disorder characterized by nonprogressive congenital cerebellar ataxia with mental retardation in 11 patients among the Dariusleut Hutterites of Alberta.

A number sign (#) is used with this entry because of evidence that this form of congenital cerebellar ataxia with mental retardation (CAMRQ4) is caused by homozygous mutation in the ATP8A2 gene (605870) on chromosome 13q12. One such family has been reported. Description Cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ) is a genetically heterogeneous disorder characterized by congenital cerebellar ataxia and mental retardation (summary by Gulsuner et al., 2011). For a discussion of genetic heterogeneity of CAMRQ, see CAMRQ1 (224050). Clinical Features Onat et al. (2013) reported a consanguineous Turkish family in which 4 individuals had a severe neurologic disorder characterized by mental retardation, dysarthria, and truncal ataxia with or without quadrupedal gait. Brain MRI showed mild atrophy of the cerebral cortex, corpus callosum, and inferior cerebellum.

A number sign (#) is used with this entry because this form of congenital cerebellar ataxia with mental retardation (CAMRQ3) is caused by homozygous mutation in the CA8 gene (114815) on chromosome 8q12. Description Cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ) is a genetically heterogeneous disorder characterized by congenital cerebellar ataxia and mental retardation (summary by Gulsuner et al., 2011). For a discussion of genetic heterogeneity of CAMRQ, see CAMRQ1 (224050). Clinical Features Turkmen et al. (2009) reported a consanguineous Iraqi family in which 4 of 8 sibs had congenital ataxia, mild mental retardation, and dysarthria. All walked with a quadrupedal gait, with straight legs and placing their weight on the palms of their hands.

Spinocerebellar ataxia type 8 (SCA8) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term) characterized by cerebellar ataxia and cognitive dysfunction in almost three quarters of patients and pyramidal and sensory signs in approximately a third of patients. Epidemiology Prevalence is unknown. However, SCA8 accounts for approximately 3% of ADCA cases. Clinical description Other features include dysexecutive disorders and commonly psychiatric disorders. Etiology SCA8 is caused by a trinucleotide repeat on 13q21 that produces a polyglutamine expansion in the ataxin 8 gene ( ATXN8 ). SCA8 is thought to result from RNA-mediated neurotoxicity. Prognosis Prognosis is relatively good.

Summary Clinical characteristics. SCA8 is a slowly progressive ataxia with disease onset typically occurring in adulthood. Onset ranges from age one to 73 years. The progression is typically over decades regardless of the age of onset. Common initial symptoms are scanning dysarthria with a characteristic drawn-out slowness of speech and gait instability; life span is typically not shortened. Some individuals present with nystagmus, dysmetric saccades and, rarely, ophthalmoplegia. Tendon reflex hyperreflexity and extensor plantar responses are present in some severely affected individuals.

Spinocerebellar ataxia type 8 (SCA8) is an inherited neurodegenerative condition characterized by slowly progressive ataxia (problems with movement, balance, and coordination). This condition typically occurs in adulthood and usually progresses over decades. Common initial symptoms include dysarthria, slow speech, and trouble walking. Some affected individuals experience nystagmus and other abnormal eye movements. Life span is typically not shortened. This condition is inherited in an autosomal dominant manner, although not all individuals with abnormalities in the disease-causing gene will develop the disease (called reduced penetrance).

Tyrosinemia type 2 is an inborn error of tyrosine metabolism characterized by hypertyrosinemia with oculocutaneous manifestations and, in some cases, intellectual deficit. Epidemiology Prevalence is unknown but less than 150 cases have been reported in the literature so far. The disease appears to be more common in Arab and Mediterranean populations. Clinical description Skin lesions occur in 80% of cases, ocular involvement in 75% of cases and neurologic findings and some degree of intellectual deficit in up to 60% of cases. Onset is variable but the ocular symptoms (redness, photophobia, excessive tearing and pain) usually develop in the first year of life.

Tyrosinemia type 2 is a genetic disorder in which individuals have elevated blood levels of the amino acid tyrosine, a building block of most proteins. This condition can affect the eyes, skin, and intellectual development. Symptoms of tyrosinemia type 2 often begin in early childhood and include excessive tearing, abnormal sensitivity to light (photophobia), eye pain and redness, and painful skin lesions on the palms and soles (palmoplantar hyperkeratosis). About 50 percent of individuals with this condition have an intellectual disability. Tyrosinemia type 2 is caused by a deficiency of the enzyme tyrosine aminotransferase, one of the enzymes required for the multi-step process that breaks down tyrosine.

Not to be confused with Hanhart syndrome . Tyrosinemia type II Other names Oculocutaneous tyrosinemia, [1] Richner-Hanhart syndrome [2] [1] : 543 Tyrosine Specialty Dermatology Causes Genetic ( autosomal recessive ) [3] Tyrosinemia type II is an autosomal recessive condition with onset between ages 2 and 4 years, when painful circumscribed calluses develop on the pressure points of the palm of the hand and sole of the foot . [4] : 512 Contents 1 Pathophysiology 2 Diagnosis 3 Treatment 4 See also 5 References 6 External links Pathophysiology [ edit ] Type II tyrosinemia is caused by a deficiency of the enzyme tyrosine aminotransferase ( EC 2.6.1.5 ), encoded by the gene TAT . Tyrosine aminotransferase is the first in a series of five enzymes that converts tyrosine to smaller molecules, which are excreted by the kidneys or used in reactions that produce energy. This form of the disorder can affect the eyes , skin , and mental development. Symptoms often begin in early childhood and include excessive tearing , abnormal sensitivity to light ( photophobia ), eye pain and redness, and painful skin lesions on the palms and soles. About half of individuals with type II tyrosinemia are also mentally challenged.

Summary Clinical characteristics. Abetalipoproteinemia typically presents in infancy with failure to thrive, diarrhea, vomiting, and malabsorption of fat. Hematologic manifestations may include acanthocytosis (irregularly spiculated erythrocytes), anemia, reticulocytosis, and hemolysis with resultant hyperbilirubinemia. Malabsorption of fat-soluble vitamins (A, D, E, and K) can result in an increased international normalized ratio (INR). Untreated individuals may develop atypical pigmentation of the retina that may present with progressive loss of night vision and/or color vision in adulthood. Neuromuscular findings in untreated individuals including progressive loss of deep tendon reflexes, vibratory sense, and proprioception; muscle weakness; dysarthria; and ataxia typically manifest in the first or second decades of life.

Abetalipoproteinemia is a very rare condition that affects fat and vitamin absorption by the intestines and liver, leading to very low LDL-cholesterol and malnutrition. Early symptoms of this condition include diarrhea, vomiting, and poor growth. Without treatment, later complications may include muscle weakness, poor night and color vision, tremors, and speech difficulties. The long-term outcome can be difficult to predict. Abetalipoproteinemia is diagnosed based on clinical exam, laboratory tests showing abnormally low cholesterol, and confirmed by genetic testing. This condition is caused by genetic variants in the MTTP gene and is inherited in an autosomal recessive pattern.

Abetalipoproteinemia is an inherited disorder that impairs the normal absorption of fats and certain vitamins from the diet. Many of the signs and symptoms of abetalipoproteinemia result from a severe shortage (deficiency) of fat-soluble vitamins (vitamins A, E, and K). The signs and symptoms of this condition primarily affect the gastrointestinal system , eyes, nervous system, and blood. The first signs and symptoms of abetalipoproteinemia appear in infancy. They often include failure to gain weight and grow at the expected rate (failure to thrive); diarrhea; and fatty, foul-smelling stools (steatorrhea).

A severe, familial hypobetalipoproteinemia characterized by permanently low levels (below the 5th percentile) of apolipoprotein B and LDL cholesterol, and by growth delay, malabsorption, hepatomegaly, and neurological and neuromuscular manifestations. Epidemiology It is very rare, with an estimated prevalence of less than 1/1,000,000. Clinical description Abetalipoproteinemia manifests during the first year of life or in young childhood. It is often associated with growth delay, hepatomegaly with steatosis, diarrhea with steatorrhea, and fat malabsorption. Spastic ataxia, atypical retinitis pigmentosa, acanthocytosis, a low level of liposoluble vitamins, and major cytolysis and even cirrhosis can occur.

"Novel mutations in SAR1B and MTTP genes in Tunisian children with chylomicron retention disease and abetalipoproteinemia". Gene . 512 (1): 28–34. doi : 10.1016/j.gene.2012.09.117 .

Familial male limited precocious puberty (FMPP) is a gonadotropin-independent familial form of male-limited precocious puberty, generally presenting between 2-5 years of age as accelerated growth, early development of secondary sexual characteristics and reduced adult height. Epidemiology FMPP is a very rare condition; prevalence is less than 1/1,000,000. Clinical description FMPP presents in boys from 2-5 years of age with precocious signs of puberty including growth acceleration, penile enlargement, acne, pubic hair and facial hair. Spontaneous erection and masturbatory behavior are commonly observed. Testicular volume is moderately increased, in contrast to central precocious puberty (see this term) where testicular volume is markedly enlarged, similar to normal puberty.

Familial male-limited precocious puberty is a condition that causes early sexual development in males; females are not affected. Boys with this disorder begin exhibiting the signs of puberty in early childhood, between the ages of 2 and 5. Signs of male puberty include a deepening voice, acne, increased body hair, underarm odor, growth of the penis and testes, and spontaneous erections. Changes in behavior, such as increased aggression and early interest in sex, may also occur. Without treatment, affected boys grow quickly at first, but they stop growing earlier than usual.

Familial male-limited precocious puberty Other names Familial sexual precocity Male-limited precocious puberty has an autosomal dominant pattern of inheritance . However, only males are affected; females with the mutant gene are not affected. Familial male-limited precocious puberty , often abbreviated as FMPP , also known as familial sexual precocity or gonadotropin-independent testotoxicosis , [1] is a form of gonadotropin -independent precocious puberty in which boys experience early onset and progression of puberty . [2] Signs of puberty can develop as early as an age of 1 year. The spinal length in boys may be short due to a rapid advance in epiphyseal maturation. It is an autosomal dominant [1] condition with a mutation of the luteinizing hormone (LH) receptor .

Testotoxicosis is a form of gonadotropin-independent precocious puberty in which boys experience early onset and progression of puberty. The disease generally presents between 2 and 4 years of age. Patients have accelerated growth, early development of secondary sexual characteristics and reduced adult height. Testotoxicosis is caused by an activating mutation of the luteinizing hormone receptor (LHCGR) gene, which leads to increased levels of sex steroids in the context of low luteinizing hormone. The condition may be sporadic or transmitted as a dominant trait. It is only expressed in males. Treatment consists of reducing hyperandrogenism in children (sexual maturation, stature), with ketoconazole or a combination of antiandrogens and aromatase inhibitors.

A rare lower urinary tract obstruction (LUTO) characterized by varying degrees of an enlarged urinary bladder, dilated ureters, hydronephrosis, and poorly contractile and disorganized detrusor and ureteral smooth muscle, in association with hypoplastic or absent midline abdominal skeletal musculature, and bilaterally undescended testes in males. Epidemiology Data on prevalence is limited. Birth prevalence is estimated in Canada and the United states at 1/29,000 and 1/26,500, respectively; 95% of cases occur in males. Clinical description The spectrum ranges from mildly affected individuals to lethality. Prune belly syndrome (PBS) often presents antenatally on routine ultrasound with oligohydramnios and a very large, distended bladder, mild to severe bilateral hydroureteronephrosis, fetal ascites and, occasionally, renal dysplasia and a patent urachus. Other anomalies include cryptorchidism, pulmonary hypoplasia, club foot and features of Potter sequence.

Prune belly syndrome Other names Abdominal muscle deficiency syndrome, congenital absence of the abdominal muscles, Eagle-Barrett syndrome, [1] Obrinsky syndrome, [2] Fröhlich syndrome, [3] triad syndrome Prune belly syndrome in an Egyptian child with Down syndrome . Specialty Medical genetics Prune belly syndrome is a rare, genetic birth defect affecting about 1 in 40,000 births. [4] About 97% of those affected are male. Prune belly syndrome is a congenital disorder of the urinary system , characterized by a triad of symptoms. The syndrome is named for the mass of wrinkled skin that is often (but not always) present on the abdomen of those with the disorder. Contents 1 Signs and symptoms 1.1 Complications 2 Diagnosis 3 Treatment 4 References 5 External links Signs and symptoms [ edit ] Prune-belly triad consists of: Cryptorchidism, abdominal wall defects and genitourinary defects: [5] A partial or complete lack of abdominal wall muscles.

Prune belly syndrome (PBS) is a condition characterized by a lack of abdominal muscles, causing the skin on the abdominal area to wrinkle and appear "prune-like"; undescended testicles in males; and urinary tract malformations. PBS is more common in males. The severity of symptoms can vary greatly from person to person. At one end of the spectrum, the condition may cause severe kidney and pulmonary (lung) problems incompatible with life (resulting in stillbirth ); at the other end of the spectrum, the condition may cause few, if any, urological abnormalities. The cause of PBS is unknown. Treatment varies, but usually includes surgical management of symptoms.

EDICT (endothelial dystrophy-iris hypoplasia-congenital cataract-stromal thinning) syndrome is a very rare eye disorder representing a constellation of autosomal dominantly inherited ocular findings, including early-onset or congenital cataracts, corneal stromal thinning, early-onset keratoconus, corneal endothelial dystrophy, and iris hypoplasia.

An extremely rare genetic congenital heart disease characterized by the presence of atrial septal defect, mostly of the ostium secundum type, associated with conduction anomalies like atrioventricular block, atrial fibrillation or right bundle branch block.

A rare mitochondrial oxidative phosphorylation disorder with complex I and IV deficiency characterized by lactic acidosis, hypotonia, hypertrophic cardiomyopathy and global developmental delay. Other clinical features include feeding difficulties, failure to thrive, seizures, optic atrophy and ataxia.

Clinical Features Nezelof et al. (1964) first reported the syndrome of T-cell deficiency with little or no abnormality of gammaglobulin. The possibility of a separate entity distinct from Bruton type agammaglobulinemia (300755), in which the tonsillar system is absent, and from severe combined immunodeficiency (SCID; see, e.g., 300400 and 601457), in which both the thymus and the tonsillar systems are absent, was postulated also by Cooper et al. (1965). In Nezelof syndrome, the defect may be limited to the thymus system which is responsible for cellular immunity. The cases of Allibone et al. (1964) may be examples. Fulginiti et al. (1966) observed 2 sisters in 1 family and a brother and sister in another family with thymic dysplasia (similar to that seen in Swiss-type agammaglobulinemia), lymphopenia and normal immunoglobulins. Three died before age 2 years of recurrent pseudomonas and monilia infections.

A rare primary immunodeficiency with autosomal or X-linked recessive inheritance, characterized by atrophy of the thymus in the absence of other congenital abnormalities, with profound T-cell deficiency, while serum immunoglobulin levels are normal or increased. Patients present with chronic or recurrent infections in infancy including candidiasis, skin, pulmonary and urinary tract infections, chronic diarrhea, and failure to thrive.

Amyloidosis is a group of diseases in which a protein, called amyloid, builds up in the body's organs and tissues. Amyloidosis AA is also referred to as Secondary amyloidosis or Inflammatory amyloidosis. This disease is caused by a long-lasting infection or inflammatory disease such as rheumatoid arthritis, familial Mediterranean fever, or osteomyelitis. Infection or inflammation in the body causes an increased amount of a specific protein called serum amyloid A (SAA) protein. In this disease, part of the SAA protein forms deposits called "amyloid fibrils".

Secondary amyloidosis is a form of amyloidosis (see this term), that complicates chronic inflammatory disorders (mainly rheumatoid arthritis, see this term) and is characterized by the aggregation and deposition of amyloid fibrils composed of serum amyloid A protein, an acute phase reactant. Although spleen, suprarenal gland, liver and gut are frequent sites of amyloid deposition, the clinical picture is dominated by renal involvement.