Limb/Pelvis-Hypoplasia/Aplasia syndrome (LPHAS) is a rare autosomal recessive disorder, characterized by a profound deficiency of the limbs, absent or hypoplastic pelvic bones, skull defects, thoracic dystrophy, unusual facies, and genital malformations. Pelvic bones show sacral agenesis or hypoplasia, whereas the skull might show a defect of the occipital bone with or without meningocele. Characteristic facial features include dysplastic and large ears, high and narrow palate, broad nasal bridge and nose, and a broad neck. Genital malformations include Mullerian aplasia, and agenesis of the uterus and vagina in females, and micropenis with cryptorchidism in males. Affected patients display normal growth and intelligence.
Most patients reported with LPHAS have been born to consanguineous parents, suggesting an autosomal recessive mode of inheritance. Linkage studies identified mutations in the WNT7A (Wingless Type MMTV Integration Site Family Member 7A) gene to be the cause of the disease. The protein product of this gene plays a major role in several developmental processes, including dorso-ventral patterning, and development of the anterior-posterior axis in the female reproductive tract.