Otopalatodigital Spectrum Disorders

The X-linked otopalatodigital (X-OPD) spectrum disorders, characterized primarily by skeletal dysplasia, include the following:

  • Otopalatodigital syndrome type 1 (OPD1)
  • Otopalatodigital syndrome type 2 (OPD2)
  • Frontometaphyseal dysplasia type 1 (FMD1)
  • Melnick-Needles syndrome (MNS)
  • Terminal osseous dysplasia with pigmentary skin defects (TODPD)

In OPD1, most manifestations are present at birth; females can present with severity similar to affected males, although some have only mild manifestations. In OPD2, females are less severely affected than related affected males. Most males with OPD2 die during the first year of life, usually from thoracic hypoplasia resulting in pulmonary insufficiency. Males who live beyond the first year of life are usually developmentally delayed and require respiratory support and assistance with feeding. In FMD1, females are less severely affected than related affected males. Males do not experience a progressive skeletal dysplasia but may have joint contractures and hand and foot malformations. Progressive scoliosis is observed in both affected males and females. In MNS, wide phenotypic variability is observed; some individuals are diagnosed in adulthood, while others require respiratory support and have reduced longevity. MNS in males results in perinatal lethality in all recorded cases. TODPD, seen only in females, is characterized by a skeletal dysplasia that is most prominent in the digits, pigmentary defects of the skin, and recurrent digital fibromata.