Meyahealth
Home
ENES
HomeGeneticsConditionsOtopalatodigital syndrome type 2
Back to Conditions
Otopalatodigital syndrome type 2
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Conditions

Otopalatodigital syndrome type 2

Otopalatodigital syndrome type 2 is a rare X‑linked disorder that produces severe skeletal, facial, and organ abnormalities, with most affected males not surviving past infancy.

Overview

Otopalatodigital syndrome type 2 is a disorder primarily involving abnormalities in skeletal development. It belongs to the otopalatodigital spectrum disorders, which also include otopalatodigital syndrome type 1, frontometaphyseal dysplasia, Melnick‑Needles syndrome, and terminal osseous dysplasia. Common features across the spectrum are hearing loss from malformations of the ear ossicles, palate abnormalities, and digital (finger‑ or toe‑) skeletal anomalies.

Clinical Features

Facial and Craniofacial Findings

  • Wide‑set, downward‑slanting eyes
  • Prominent brow ridges
  • Broad, flat nose
  • Very small lower jaw and chin (micrognathia)
  • Possible opening in the roof of the mouth (cleft palate)

Digital and Skeletal Abnormalities

  • Camptodactyly (curvature of the fingers)
  • Shortened or absent thumbs and big toes
  • Short stature
  • Bow‑shaped (curved) bones of the arms and legs
  • Absent or abnormal bones, including underdeveloped ribs that can impair breathing

Additional Systemic Involvement

  • Developmental delay
  • Hydrocephalus (increased fluid in the brain)
  • Heart defects
  • Chest wall abnormalities
  • Ureteral obstruction
  • Hypospadias in males (urethral opening on the underside of the penis)
  • Potential hearing loss

Sex‑Specific Severity

Males with otopalatodigital syndrome type 2 generally exhibit far more severe signs and symptoms than females and typically do not survive past infancy because of respiratory failure due to an underdeveloped rib cage.

Frequency

Otopalatodigital syndrome type 2 is a rare disorder, affecting fewer than 1 in every 100,000 individuals. Its specific incidence is unknown.

Causes & Risk Factors

The condition is caused by mutations in the FLNA gene, which encodes the protein filamin A. Filamin A forms part of the cellular cytoskeleton by binding to actin and linking actin to other proteins, thereby providing structural support and enabling cell shape changes and movement.

All pathogenic FLNA mutations associated with otopalatodigital syndrome type 2 occur in the actin‑binding region of filamin A and are described as “gain‑of‑function,” leading to increased actin binding. These mutations likely destabilize the cytoskeleton and disrupt cellular processes essential for skeletal development, although the precise mechanisms linking the protein changes to the clinical phenotype remain unknown.

Gene Information

  • FLNA

Inheritance

The disorder follows an X‑linked inheritance pattern. The mutated gene resides on the X chromosome. In males (who have a single X chromosome), a mutation in the sole copy of the gene is sufficient to cause the condition. In females (who have two X chromosomes), a mutation in one copy may result in milder features or no symptoms at all. Fathers cannot transmit X‑linked traits to their sons.

Other Names

  • Cranioorodigital syndrome
  • Faciopalatoosseous syndrome
  • FPO
  • OPD syndrome, type 2
  • Oto‑palato‑digital syndrome, type II
  • Taybi syndrome

Additional Information & Resources

Genetic Testing

  • Genetic Testing Registry: Oto‑palato‑digital syndrome, type II

Rare Disease Information

  • Genetic and Rare Diseases Information Center: Otopalatodigital syndrome type 2

Patient Support

  • National Organization for Rare Disorders (NORD)

Reference Catalogs

  • OMIM: OTOPALATODIGITAL SYNDROME, TYPE II; OPD2

Scientific Literature

  • PubMed

References

  • Batra P, Ryan FS, Witherow H, Calvert ML. Distraction in a case of otopalatodigital syndrome type II. Int J Paediatr Dent. 2006 Jul;16(4):286-91. doi: 10.1111/j.1365-263X.2006.00714.x.
  • Marino‑Enriquez A, Lapunzina P, Robertson SP, Rodriguez JI. Otopalatodigital syndrome type 2 in two siblings with a novel filamin A 629G>T mutation: clinical, pathological, and molecular findings. Am J Med Genet A. 2007 May 15;143A(10):1120-5. doi: 10.1002/ajmg.a.31696.
  • Moutton S, et al. 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.
  • Murphy‑Ryan M, Babovic‑Vuksanovic D, Lindor N. Bifid tongue, corneal clouding, and Dandy‑Walker malformation in a male infant with otopalatodigital syndrome type 2. Am J Med Genet A. 2011 Apr;155A(4):855-9. doi: 10.1002/ajmg.a.33901.
  • Naudion S, et al. Fetal phenotypes in otopalatodigital spectrum disorders. Clin Genet. 2016 Mar;89(3):371-7. doi: 10.1111/cge.12679.
  • Robertson S, Wade E. FLNA‑Related Otopalatodigital Spectrum Disorders. GeneReviews® [Internet]. 2005 Nov 30 [updated 2025 Jun 26].
  • Robertson SP, et al. 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.
  • 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.

Frequently Asked Questions

Clinicians assess for a small, flat nose with a broad nasal bridge, downward‑slanting eyes, a very small lower jaw (micrognathia), and a cleft palate or a small opening in the roof of the mouth. Skeletal anomalies include bowed long bones, shortened or absent thumbs and big toes, and abnormal rib development that can make the chest wall appear narrow or misshapen. These features, combined with a history of hearing loss or heart defects, raise suspicion for the syndrome.
The FLNA gene encodes filamin A, a protein essential for cytoskeletal organization during bone formation. Mutations disrupt rib development, leading to an under‑developed or misshapen rib cage that compromises lung expansion. Infants may require mechanical ventilation or positive pressure support from birth, and in some cases surgical stabilization of the chest wall or thoracic expansion procedures may be considered to improve breathing. Early respiratory assessment and planning are critical.
Otopalatodigital syndrome type 2 is inherited in an X‑linked dominant pattern. Males with the mutation usually do not survive infancy, while females may be carriers or affected. Each pregnancy has a 50 % chance of inheriting the mutation if a parent is a carrier. Genetic testing options include targeted sequencing of the FLNA gene, karyotyping for larger rearrangements, and pre‑implantation genetic testing (PGT) during in vitro fertilization to select embryos without the mutation. Prenatal testing via CVS or amniocentesis can also detect the mutation early in pregnancy.
Cleft palate repair is usually performed within the first year of life to improve feeding and speech development. Hearing loss can be managed with hearing aids, and if the loss is conductive, surgical correction of ear ossicle malformations may be possible. In cases of sensorineural loss, cochlear implantation can be considered. Additionally, if hydrocephalus or heart defects are present, neurosurgical or cardiac interventions may be necessary to support overall development.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

Meyahealth

Ⓒ 2026. All rights reserved by MEYA

About UsTerms & PolicyFAQ