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.

Otopalatodigital syndrome type 1 is a rare disorder, affecting fewer than 1 in every 100,000 individuals. Its specific incidence is unknown.

Otopalatodigital syndrome type 1 is caused by mutations in the FLNA gene. The FLNA gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin A attaches (binds) to another protein called actin, and helps the actin to form the branching network of filaments that make up the cytoskeleton. Filamin A also links actin to many other proteins to perform various functions within the cell.

The FLNA gene mutations that cause otopalatodigital syndrome type 1 result in changes to the filamin A protein in the region that binds to actin. The mutations are described as "gain-of-function" because they appear to lead to a protein with an increased ability to bind to actin. Researchers believe that the mutations impair the stability of the cytoskeleton and disrupt cellular processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of otopalatodigital syndrome type 1.

Genetic Testing Information

• Genetic Testing Registry: Oto-palato-digital syndrome, type I

Genetic and Rare Diseases Information Center

• Otopalatodigital syndrome type 1

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• OTOPALATODIGITAL SYNDROME, TYPE I; OPD1

Scientific Articles on PubMed

• PubMed

• Hidalgo-Bravo A, Pompa-Mera EN, Kofman-Alfaro S, Gonzalez-Bonilla CR, Zenteno JC. A novel filamin A D203Y mutation in a female patient with otopalatodigital type 1 syndrome and extremely skewed X chromosome inactivation. Am J Med Genet A. 2005 Jul 15;136(2):190-3. doi: 10.1002/ajmg.a.30792. Citation on PubMed
• Joksic I, Cuturilo G, Jurisic A, Djuricic S, Peterlin B, Mijovic M, Karadzov ON, Egic A, Milovanovic Z. Otopalatodigital Syndrome Type I: Novel Characteristics and Prenatal Manifestations in two Siblings. Balkan J Med Genet. 2019 Dec 21;22(2):83-88. doi: 10.2478/bjmg-2019-0024. eCollection 2019 Dec. Citation on PubMed or Free article on PubMed Central
• Moutton S, Fergelot P, Naudion S, Cordier MP, Sole G, Guerineau E, Hubert C, Rooryck C, Vuillaume ML, Houcinat N, Deforges J, Bouron J, Deves S, Le Merrer M, David A, Genevieve D, Giuliano F, Journel H, Megarbane A, Faivre L, Chassaing N, Francannet C, Sarrazin E, Stattin EL, Vigneron J, Leclair D, Abadie C, Sarda P, Baumann C, Delrue MA, Arveiler B, Lacombe D, Goizet C, Coupry I. Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum. J Hum Genet. 2016 Aug;61(8):693-9. doi: 10.1038/jhg.2016.37. Epub 2016 May 19. Citation on PubMed
• Robertson S. X-Linked Otopalatodigital Spectrum Disorders. 2005 Nov 30 [updated 2019 Oct 3]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1393/ Citation on PubMed
• Robertson SP, Twigg SR, Sutherland-Smith AJ, Biancalana V, Gorlin RJ, Horn D, Kenwrick SJ, Kim CA, Morava E, Newbury-Ecob R, Orstavik KH, Quarrell OW, Schwartz CE, Shears DJ, Suri M, Kendrick-Jones J, Wilkie AO; OPD-spectrum Disorders Clinical Collaborative Group. Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans. Nat Genet. 2003 Apr;33(4):487-91. doi: 10.1038/ng1119. Epub 2003 Mar 3. Citation on PubMed
• Robertson SP. Otopalatodigital syndrome spectrum disorders: otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick-Needles syndrome. Eur J Hum Genet. 2007 Jan;15(1):3-9. doi: 10.1038/sj.ejhg.5201654. Epub 2006 Aug 23. Citation on PubMed