DISEASE CARD

Definition

Limb-mammary syndrome (LMS) is a rare autosomal dominant disorder characterized by ectrodactyly and hypoplastic breasts/nipples. An association with TP63 gene mutations (chromosome 3q28) was first described in 1999.¹

Further mutations in this transcription factor have been identified in other ectodermal dysplasia syndromes with similar features, including ADULT syndrome (acro-dermato-ungual-lacrimal-tooth; OMIM 103285), AEC syndrome (ankyloblepharon-ectodermal dysplasia-clefting; Hay Wells; OMIM 106260), 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 (congenital abnormality involving the absence or deficiency of one or more fingers or toes), also known as split hand/foot malformation, with varying degree of severity as well as syndactyly. This feature is present in up to 85% of individuals. Hypoplasia/aplasia of breasts (in females) and/or nipples is the second prominent feature and may present symmetric or asymmetric. It is also seen in ADULT syndrome, a similar TP63 related disorder with several overlapping features, but not in other TP63 related disorders. Additional clinical features of LMS may include lacrimal-duct atresia (presenting with chronic conjunctivitis, blepharitis in childhood) in about 50% of patients, nail dysplasia, hypohidrosis and hypodontia (reduced number of teeth). Patients may present with cleft lip (with or without cleft palate). Otherwise, hair and skin are normal.^{1, 2}

Table: TP63-related Disorders ³

Pathogenesis

Mutations in the TP63 gene have been identified as the molecular basis of LMS. The p63 protein 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 hair, teeth or nails fail to develop normally. Identification of a p63 gene mutation will help confirm the diagnosis.

Treatment

Limb, mammary gland and cleft palate deformities usually require corrective surgical procedures. Specialists should be consulted early on. Dental assessment is important as many individuals require successive dentures as a child with addition of dental implants and bridges later in adult life. Topical emollients are indicated for dry, eczematous skin and many affected individuals require ophthalmological consultation due to lacrimal duct abnormalities.

References