Immunodeficiency, and Coarctation of aorta

DiGeorge syndrome (DGS) comprises hypocalcemia arising from parathyroid hypoplasia, thymic hypoplasia, and outflow tract defects of the heart. Disturbance of cervical neural crest migration into the derivatives of the pharyngeal arches and pouches can account for the phenotype. Most cases result from a deletion of chromosome 22q11.2 (the DiGeorge syndrome chromosome region, or DGCR). Several genes are lost including the putative transcription factor TUPLE1 which is expressed in the appropriate distribution. This deletion may present with a variety of phenotypes: Shprintzen, or velocardiofacial, syndrome (VCFS ); conotruncal anomaly face (or Takao syndrome); and isolated outflow tract defects of the heart including tetralogy of Fallot, truncus arteriosus, and interrupted aortic arch. A collective acronym CATCH22 has been proposed for these differing presentations. A small number of cases of DGS have defects in other chromosomes, notably 10p13 (see {601362}). In the mouse, a transgenic Hox A3 (Hox 1.5) knockout produces a phenotype similar to DGS as do the teratogens retinoic acid and alcohol.

DIGEORGE SYNDROME; DGS Is also known as hypoplasia of thymus and parathyroids|chromosome 22q11.2 deletion syndrome|third and fourth pharyngeal pouch syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Hearing impairment

SOURCES: OMIM MENDELIAN

Kabuki syndrome is a congenital mental retardation syndrome with additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids (reminiscent of the make-up of actors of Kabuki, a Japanese traditional theatrical form), a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy (Niikawa et al., 1981). Genetic HeterogeneityKabuki syndrome-2 (OMIM ) is caused by mutation in the KDM6A gene (OMIM ) on chromosome Xp11.3.

KABUKI SYNDROME 1; KABUK1 Is also known as kabuki syndrome|kabuki make-up syndrome|kms|niikawa-kuroki syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM MENDELIAN

Rubinstein-Taybi syndrome is a multiple congenital anomaly syndrome characterized by mental retardation, postnatal growth deficiency, microcephaly, broad thumbs and halluces, and dysmorphic facial features. The facial appearance is striking, with highly arched eyebrows, long eyelashes, downslanting palpebral fissures, broad nasal bridge, beaked nose with the nasal septum, highly arched palate, mild micrognathia, and characteristic grimacing or abnormal smile. Affected individuals also have an increased risk of tumor formation (Rubinstein and Taybi, 1963; review by Hennekam, 2006).Floating-Harbor syndrome (OMIM ), which shows phenotypic overlap with Rubinstein-Taybi syndrome, is caused by mutation in the SRCAP gene (OMIM ), a coactivator for CREBBP. Genetic Heterogeneity of Rubinstein-Taybi SyndromeRubinstein-Taybi syndrome-1 (RSTS1) constitutes about 50 to 70% of patients with the disorder. Rubinstein-Taybi syndrome-2 (RSTS2 ) comprises about 3% of patients and is primarily due to de novo heterozygous mutation in the EP300 gene (OMIM ) on chromosome 22q13 (Bartsch et al., 2010).See also chromosome 16p13.3 deletion syndrome (OMIM ), a severe form of Rubinstein-Taybi syndrome resulting from a contiguous gene deletion involving the CREBBP gene as well as other neighboring genes.

RUBINSTEIN-TAYBI SYNDROME 1; RSTS1 Is also known as broad thumbs and great toes, characteristic facies, and mental retardation|rubinstein syndrome|rsts|broad thumb-hallux syndrome

• Intellectual disability
• Seizures
• Short stature
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM MENDELIAN

Jacobsen syndrome is a multiple congenital anomaly/mental retardation (MCA/MR) contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11.

JACOBSEN SYNDROME Is also known as monosomy 11qter|del(11)(q23.3)|distal deletion 11q|telomeric deletion 11q|distal monosomy 11q|del(11)(qter)|chromosome 11q deletion syndrome|partial 11q monosomy syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM ORPHANET MENDELIAN

Mendelian susceptibility to mycobacterial diseases (MSMD) due to complete interleukin-12 subunit beta (IL12B) deficiency is a genetic variant of MSMD (see this term) characterized by mild bacillus Calmette-Guérin (BCG) infections and recurrent Salmonella infections.

MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASES DUE TO COMPLETE IL12B DEFICIENCY Is also known as mendelian susceptibility to mycobacterial diseases due to complete interleukin 12b deficiency|msmd due to complete interleukin 12b deficiency|msmd due to complete il12b deficiency|il12b deficiency

• Immunodeficiency
• Lymphadenopathy

SOURCES: ORPHANET OMIM MENDELIAN

IMMUNODEFICIENCY, COMMON VARIABLE, 5; CVID5 Is also known as antibody deficiency due to cd20 defect

• Immunodeficiency
• Recurrent respiratory infections
• Respiratory tract infection
• Decreased antibody level in blood
• Recurrent bacterial infections

SOURCES: OMIM MENDELIAN

• Respiratory distress
• Immunodeficiency

SOURCES: OMIM MENDELIAN

Mendelian susceptibility to mycobacterial diseases (MSMD) due to partial IRF8 (interferon regulatory factor 8) deficiency is a rare genetic variant of MSMD (see this term) characterized by a selective susceptibility to relatively mild infections with bacillus Calmette-Guérin (BCG)..

MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASES DUE TO PARTIAL IRF8 DEFICIENCY Is also known as msmd due to partial interferon regulatory factor 8 deficiency|msmd due to partial irf8 deficiency|irf8 deficiency, autosomal dominant|mendelian susceptibility to mycobacterial diseases due to partial interferon regulatory factor 8 deficiency|immunodeficie

• Fever
• Immunodeficiency
• Recurrent infections
• Lymphadenopathy
• Abnormality of immune system physiology

SOURCES: OMIM ORPHANET MENDELIAN

Pyogenic bacterial infection due to MyD88 deficiency is a primary immunodeficiency characterized by increased susceptibility to pyogenic bacterial infections, including invasive pneumococcal, invasive staphylococcal and pseudomonas disease.

PYOGENIC BACTERIAL INFECTIONS DUE TO MYD88 DEFICIENCY Is also known as myd88 deficiency|pyogenic bacterial infections, recurrent, due to myd88 deficiency|recurrent pyogenic bacterial infections due to myd88 deficiency

• Fever
• Immunodeficiency
• Recurrent bacterial skin infections

SOURCES: MESH OMIM ORPHANET MENDELIAN

Distal 22q11.2 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the long arm of chromosome 22, with a highly variable phenotype characterized by prematurity, pre- and post-natal growth retardation, developmental delay (particularly speech), mild intellectual disability, variable cardiac defects, and minor skeletal anomalies (such as clinodactyly). Dysmorphic features include prominent forehead, arched eyebrows, deep set eyes, narrow upslanting palpebral fissures, ear abnormalities, hypoplastic alae nasi, smooth philtrum, down-turned mouth, thin upper lip, retro/micrognatia and pointed chin. For certain very distal deletions, there is a risk of developing malignant rhabdoid tumours.

DISTAL 22Q11.2 MICRODELETION SYNDROME Is also known as distal del(22)(q11.2)|distal monosomy 22q11.2

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Microcephaly

SOURCES: ORPHANET MENDELIAN