Terminal osseous dysplasia with pigmentary defects
TODPD demonstrates wide phenotypic variability. Clinical features include atrophic pigmented plaques on the face and scalp, skeletal abnormalities of the limbs, and digital fibromatosis in infancy and childhood. Other less common findings include joint contractures, dysmorphic facial features, colobomas of the iris, more than one oral frenulum, and urogenital and cardiac abnormalities.
Digital fibromas are the most prominent and common feature of TODPD and are observed between birth (see infantile digital fibromatosis) and age 5. These fibromas are often recurrent after surgical excision, but they tend to resolve with age, and so are an infrequent finding in adults. Another cutaneous finding is the presence of hyperpigmented, atrophic papules and plaques that are often found on the face, particularly the temporal regions, malar regions, and scalp. There may be associated alopecia. Skin lesions in TODPD may not appear until late childhood or early adulthood.
Skeletal findings in TODPD include abnormal ossification of the bones of the hands and feet, brachydactyly, and clinodactyly. Metacarpal bones may be shortened and irregularly shaped with fusion at the base or with the carpal bones. Bowing and mesomelic shortening of the long bones may also be seen.
TODPD is caused by a mutation in exon 31 of the FLNA gene that encodes the filamin A protein, a cytoplasmic protein that links actin filaments to membrane glycoproteins and participates in modeling of the cytoskeleton. Given the wide phenotypic variation of the disease, it is thought that mutations implicated in TODPD involve X-inactivation. TODPD is the only FLNA-related disorder that has been reported with skin findings.
For more information, see OMIM.
Q87.2 – Congenital malformation syndromes predominantly involving limbs
723578001 – Terminal osseous dysplasia and pigmentary defect syndrome
- Infantile digital fibromatosis – characteristically spares the thumbs and great toes; no associated skeletal abnormalities are present
- Juvenile hyaline fibromatosis
- Supernumerary digit
- Focal dermal hypoplasia (ie, Goltz syndrome) – no digital fibromas; characterized by linear atrophic streaks with telangiectasias on the trunk and extremities
- Aplasia cutis
- Nevus sebaceus
- Setleis syndrome
- Melnick-Needles syndrome
- Otopalatodigital syndrome
- Microphthalmia with linear skin defects (MLS)
- Oculocerebrocutaneous syndrome (OCCS)