DISEASE CARD

Definition

Limb-mammry syndrome (LMS) is a rare autosomal dominant disorder characterized by ectrodactyly (congenital abnormality involving the absence of some fingers or toes) and hypoplastic breasts/nipples. An association with p63 gene mutations was first described by Van Bokhoven et al. in 1999. Mutations in this transcription factor have also been identified in other ectodermal dysplasia syndromes including AEC (ankyloblepharon-ectodermal dysplasia-clefting; Hay Wells; OMIM 106260) syndrome, EEC (ectrodactyly, ectodermal dysplasia, cleftting; OMIM 129900), split-hand split-foot malformation syndrome (OMIM 605289) and Rapp-Hodgkin syndrome (OMIM 129400).

Clinical Description

Infants are born with ectrodactyly and hypoplasia/aplasia of breasts and/or nipples. Additional clinical features may include lacrimal-duct atresia, nail dysplasia, hypohidrosis, hypodontia, and cleft palate with or without bifid uvula.

Pathogenesis

Mutations in the p63 gene have been identified as the molecular basis of LMS. The p63 gene is a p53 homolog and is an important transcription factor in the development of skin and ectodermal structures.

Diagnosis

Diagnosis is usually made by assessment of the clinical features either at, or soon after birth. In those individuals with milder phenotypes, the diagnosis may only become evident when the hair, teeth or nails fail to develop normally. If a p63 gene mutation is identified, this will help confirm the diagnosis. No other diagnostic tests are available at present.

Treatment

Limb, mammary gland and cleftlip/palate deformities require corrective surgical procedures. Dental treatment is extremely important as many individuals require successive dentures as a child with addition of dental implants and bridges later in adult life. Topical emollients are required to treat dry, eczematous areas of skin and many affected individuals require ophthalmological review regarding lacrimal duct abnormalities.