Otopalatodigital Syndrome, Type Ii (OPD2)

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OMIM 57 304120 Orphanet 59 ORPHA90652 MESH via Orphanet 45 C538089 UMLS via Orphanet 74 C1844696

ICD10 via Orphanet 34 Q87.0 MedGen 42 C1844696 SNOMED-CT via HPO 69 204878001 204888000 43064006 14582003 3639002 63567004 87979003 4602007 230745008 276709006 194021007 22006008 32958008 253251006 103276001 15188001 343087000 95828007 95515009 253255002 44057004 246800008 128306009 193570009 247053007 16958000 26624006 391987005 249696007 249671009 204113001 413728006 205131007 228156007 247578003 91138005 224958001 16026008 48334007 52781008 295091000119100 36440009 432788009 18735004 368009 253273004 396351009 59494005 32113001 205082007 205359003 90145001 253101008 48777005 55999004 80825009 409623005 203994003 414667000 113194005 111266001 64217002 105985007 240190009 409622000 125617002 417558002 249310005 240221008 237364002 276507005 237836003 20018005 27173008 253936008 49347007 249773003 205135003 202281000 more UMLS 73 C0265251

NIH Rare Diseases : ⁵³ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 90652Disease definitionOtopalatodigital syndrome type 2 (OPD2) is 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.EpidemiologyTo date, more than 40 cases of OPD2 have been described in the literature.Clinical descriptionOPD2 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.EtiologyOPD2 is caused by gain of function mutations in the geneFLNA (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 counselingOPD2 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 oto-palato-digital syndrome, type ii, is related to rubinstein-taybi syndrome 2 and rubinstein-taybi syndrome 1. An important gene associated with Otopalatodigital Syndrome, Type Ii is FLNA (Filamin A). Affiliated tissues include bone, heart and brain, and related phenotypes are malar flattening and hypertelorism

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.

OMIM : ⁵⁷ 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 : ⁷⁵ 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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