Otopalatodigital Syndrome, Type I (OPD1)

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MedlinePlus Genetics: ⁴² Otopalatodigital syndrome type 1 is a disorder primarily involving abnormalities in skeletal development. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 2, frontometaphyseal dysplasia, Melnick-Needles syndrome, and terminal osseous dysplasia. 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 or toes (digits).Otopalatodigital syndrome type 1 is usually the mildest of the otopalatodigital spectrum disorders. People with this condition usually have characteristic facial features including wide-set and downward-slanting eyes; prominent brow ridges; and a broad, flat nose. Affected individuals have abnormalities of the fingers and toes, such as blunt, square-shaped (spatulate) fingertips; shortened thumbs and big toes; unusually long second toes; and a wide gap between the first and second toes (known as a sandal gap). Affected individuals also have hearing loss.Infants with otopalatodigital syndrome type 1 may be born with an opening in the roof of the mouth (a cleft palate). Individuals with this condition often have fewer teeth than normal (hypodontia). They may have mild abnormal curvature (bowing) of their limbs, and limited range of motion in some joints. People with otopalatodigital syndrome type 1 may be somewhat shorter than other members of their family.Females with otopalatodigital syndrome type 1 often have more variable signs and symptoms compared to affected males, with females typically having fewer signs and symptoms.

MalaCards based summary: Otopalatodigital Syndrome, Type I, also known as otopalatodigital syndrome type 1, is related to rubinstein-taybi syndrome 1 and otopalatodigital syndrome, type ii. An important gene associated with Otopalatodigital Syndrome, Type I is FLNA (Filamin A), and among its related pathways/superpathways are Chromatin organization and Pre-NOTCH Expression and Processing. The drugs Valproic acid and Neurotransmitter Agents have been mentioned in the context of this disorder. Affiliated tissues include bone, heart and spinal cord, and related phenotypes are hearing impairment and skeletal dysplasia

OMIM®: ⁵⁷ Otopalatodigital syndrome-1 is 1 of 4 otopalatodigital syndromes caused by mutations in the FLNA gene. The disorders, which include frontometaphyseal dysplasia (FMD1; 305620), otopalatodigital syndrome-2 (OPD2; 304120), 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.' (311300) (Updated 08-Dec-2022)

UniProtKB/Swiss-Prot: ⁷³ X-linked dominant multiple congenital anomalies disease mainly characterized by a generalized skeletal dysplasia, mild intellectual disability, hearing loss, cleft palate, and typical facial anomalies. OPD1 belongs to a group of X-linked skeletal dysplasias known as oto- palato-digital syndrome spectrum disorders that also include OPD2, Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. FLNA is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers. Males with OPD1 have cleft palate, malformations of the ossicles causing deafness and milder bone and limb defects than those associated with OPD2. Obligate female carriers of mutations causing both OPD1 and OPD2 have variable (often milder) expression of a similar phenotypic spectrum.

Disease Ontology: ¹¹ An otopalatodigital syndrome spectrum disorder characterized by cleft palate, mild skeletal anomalies including digital anomalies, and conductive deafness caused by ossicular anomalies that has material basis in heterozygous or hemizygous mutation in exon 3, 4, or 5 of FLNA on chromosome Xq28.

GARD: ¹⁹ A disorder that is the mildest form of otopalatodigital syndrome spectrum disorder, and is characterized by a generalized skeletal dysplasia, mild intellectual disability, conductive hearing loss, and typical facial anomalies.

Orphanet: ⁵⁸ A disorder that is the mildest form of otopalatodigital syndrome spectrum disorder, and is characterized by a generalized skeletal dysplasia, mild intellectual disability, conductive hearing loss, and typical facial anomalies.

Wikipedia: ⁷⁵ Rubinstein-Taybi syndrome (RTS) is a rare genetic condition characterized by short stature, moderate to... more...

Clinical features from OMIM®:

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