Otopalatodigital Syndrome, Type Ii (OPD2)

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Disease Ontology 12 DOID:0111784 OMIM 56 304120 MeSH 43 C538089 SNOMED-CT 67 42432003 MESH via Orphanet 44 C538089 ICD10 via Orphanet 33 Q87.0

UMLS via Orphanet 72 C1844696 Orphanet 58 ORPHA90652 MedGen 41 C1844696 SNOMED-CT via HPO 68 103276001 105985007 111266001 113194005 125617002 128306009 14582003 15188001 16026008 16958000 18735004 193570009 194021007 20018005 202281000 203994003 204113001 204878001 204888000 205082007 205131007 205135003 205359003 22006008 224958001 228156007 230745008 237364002 237836003 240190009 240221008 246800008 247053007 247578003 249310005 249671009 249696007 249773003 253101008 253251006 253255002 253273004 253936008 26624006 27173008 276507005 276709006 295091000119100 32113001 32958008 343087000 3639002 36440009 368009 391987005 396351009 409622000 409623005 413728006 414667000 417558002 43064006 432788009 44057004 4602007 48334007 48777005 49347007 52781008 55999004 59494005 63567004 64217002 80825009 87979003 90145001 91138005 95515009 95828007 more UMLS 71 C0265251 C1844696

NIH Rare Diseases : ⁵² The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 90652 Definition A severe form of otopalatodigital syndrome spectrum disorder, and is characterized by dysmorphic facies, severe skeletal dysplasia affecting the axial and appendicular skeleton, extraskeletal anomalies (including malformations of the brain, heart, genitourinary system , and intestine) and poor survival. Epidemiology To date, more than 40 cases of Otopalatodigital syndrome type 2 (OPD2) have been described in the literature. Clinical description OPD2 is a congenital disorder. Intrauterine growth is usually normal and affected infants have large anterior fontanels, and facial dysmorphism including broad forehead and lateral fullness of the supraorbital ridge, hypertelorism, downslanting palpebral fissures, stubby nose with a flat root, midfacial hypoplasia, microstomia (with typical down turned bow of the upper lip), micrognathia , Pierre Robin sequence, posterior cleft palate (submucosal cleft palate or cleft velum), glossoptosis, malformed and/or apparently low-set ears. Additional features include skeletal anomalies: pectus deformity, short limbs, campomelia, fibular agenesis, flexion contractures of elbows, knees, rocker bottom or equinovarus feet, syndactyly (usually involving fingers III and IV in the hands and toes II to V in the feet), camptodactyly of fingers, and absent halluces. Extraskeletal malformations include malformations of the central nervous system (myelomeningocele /encephalocele, cerebellar hypoplasia, hydrocephalus ), heart (congenital valvular heart defects), intestine, genitourinary system (hydronephrosis ? urethral valve/reflux, hypospadias, epispadias). Congenital corneal opacities, bilobed tongue, deafness, and Dandy-Walker malformation have been reported in a minority of OPD2 cases. Congenital glaucoma and cataracts have been described in one patient. Psychomotor development varies from normal to mild intellectual disability . Carrier females with OPD2 can be asymptomatic or exhibit a phenotype that can extend from a mild subclinical osteodysplasia to a presentation indistinguishable from that of affected males. Prognosis of OPD2 is poor and perinatal death is common, secondary to cardio respiratory failure. Etiology OPD2 is caused by gain of function mutations in the gene FLNA (Xq28) that encodes filamin A. However the pathogenesis is still elusive. OPD2 is allelic with 4 other skeletal dysplasias (OPD1, Melnick-Needles syndrome (MNS), terminal osseous dysplasia - pigmentary defects (TOD) and frontometaphyseal dysplasia (FMD)). Genetic counseling OPD2 is inherited in an X-linked dominant manner. Male-to-male transmission has not been reported. The chance of transmitting the mutation in each pregnancy is 50%; males inheriting the mutation will be affected while females who inherit the mutation are less severely affected. Visit the Orphanet disease page for more resources.

MalaCards based summary : Otopalatodigital Syndrome, Type Ii, also known as otopalatodigital syndrome type 2, is related to frontometaphyseal dysplasia and atelosteogenesis. An important gene associated with Otopalatodigital Syndrome, Type Ii is FLNA (Filamin A), and among its related pathways/superpathways are Cytoskeletal Signaling and Salmonella infection (KEGG). The drugs Valproic acid and Psychotropic Drugs have been mentioned in the context of this disorder. Affiliated tissues include heart, bone and brain, and related phenotypes are hearing impairment and skeletal dysplasia

Disease Ontology : ¹² An otopalatodigital syndrome spectrum disorder characterized by disabling skeletal anomalies and variable malformations in the hindbrain, heart, intestines, and kidneys that frequently lead to perinatal death in males and less severe phenotypes in females that has material basis in hemizygous or heterozygous mutation in exons 3, 4 ,or 5 in males or exons 28 or 29 in females of FLNA on chromosome Xq28.

Genetics Home Reference : ²⁵ Otopalatodigital syndrome type 2 is a disorder involving abnormalities in skeletal development and other health problems. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, frontometaphyseal dysplasia, and Melnick-Needles syndrome. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers and/or toes (digits). Otopalatodigital syndrome type 2 also tends to cause problems in other areas of the body, such as the brain and heart. People with otopalatodigital syndrome type 2 have characteristic facial features including wide-set and downward-slanting eyes; prominent brow ridges; a broad, flat nose; and a very small lower jaw and chin (micrognathia). The base of the skull may be thickened. Some people with this disorder have hearing loss. Affected individuals are usually of short stature and may have abnormalities of the fingers and toes, such as unusual curvature of the fingers (camptodactyly) and shortened or absent thumbs and big toes. They may have bowed limbs; underdeveloped, irregular ribs that may cause problems with breathing; and other abnormal or absent bones. Some may be born with an opening in the roof of the mouth (a cleft palate). In addition to skeletal abnormalities, individuals with otopalatodigital syndrome type 2 may have developmental delay, increased fluid in the center of the brain (hydrocephalus), protrusion of the abdominal organs through the navel (omphalocele), heart defects, chest abnormalities, obstruction of the ducts between the kidneys and bladder (ureters), and, in males, opening of the urethra on the underside of the penis (hypospadias). Males with otopalatodigital syndrome type 2 generally have much more severe signs and symptoms than do females. Males with the disorder usually do not live beyond their first year, because their underdeveloped rib cage does not allow sufficient lung expansion for breathing.

OMIM : ⁵⁶ Otopalatodigital syndrome-2 is 1 of 4 otopalatodigital syndromes caused by mutations in the FLNA gene. The disorders, which include frontometaphyseal dysplasia (FMD1; 305620), otopalatodigital syndrome-1 (OPD1; 311300), and Melnick-Needles syndrome (MNS; 309350), constitute a phenotypic spectrum. At the mild end of the spectrum, males with OPD1 have cleft palate and mild skeletal anomalies with conductive deafness caused by ossicular anomalies. FMD is characterized by a generalized skeletal dysplasia, deafness and urogenital defects. Males with OPD2 have disabling skeletal anomalies in addition to variable malformations in the hindbrain, heart, intestines, and kidneys that frequently lead to perinatal death. The most severe phenotype, MNS, is characterized by a skeletal dysplasia in the heterozygote. Affected males exhibit severe malformations similar to those observed in individuals with OPD2, resulting in prenatal lethality or death in the first few months of life (review by Robertson, 2005). Verloes et al. (2000) suggested that these disorders constitute a single entity, which they termed 'frontootopalatodigital osteodysplasia.' (304120)

UniProtKB/Swiss-Prot : ⁷³ Otopalatodigital syndrome 2: Congenital bone disorder that is characterized by abnormally modeled, bowed bones, small or absent first digits and, more variably, cleft palate, posterior fossa brain anomalies, omphalocele and cardiac defects.

Clinical features from OMIM:

304120

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