Limb-mammary syndrome (LMS) associated with internal female genitalia dysgenesia: a new genotype/phenotype correlation?

摘要

EEC syndrome (ectrodactyly-ectodermal dysplasia and cleft lip/palate, OMIM 604292) is an autosomal dominant disorder involving tissues of epithelial mesenchyme origin and is characterized by ectro-dactyly (split-hand and split-foot malformation); anomalies of the skin, hair, teeth and nails; cleft palate (CP) with or without cleft lip (CL). LMS syndrome (limb-mammary syndrome, OMIM 603543) is a condition whose features overlap EEC and is characterized by ectrodactyly, mammary-gland and nipple hypoplasia, cleft palate without cleft lip, and absence of hair and skin defects [van Bokhoven et al, 19991. Other common manifestations of related conditions include lacrimal duct stenosis, conductive hearing loss, and structural urogenital anomalies [Roelfsema and Cobben, 1996; Rinne et al., 2006]. Heterozygous mutations in the TP63 gene of chromosome 3q27 [van Bokhoven et al., 19991 are associated with all reported cases of LMS syndrome and most cases with EEC syndrome. The TP63 gene encodes various isoforms of the transcription factor p63; the variants hold different functional roles in the developing epidermis [Yang et al., 1998; Wu et al., 20031. Expression of p63 mRNAs is not restricted to the skin; it has been detected in a variety of other tissues including placenta, skeletal muscle, heart, thymus, trachea, gonads and uterus [Osada et al., 1998; Dellavalle et al., 2001].