The extreme Spectrum of Pallister-Hall syndrome

Abstract

Pallister-Hall syndrome can result from GLI 3 gene mutation and is characterized by hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly. It has a wide spectrum of severity, from perinatal lethal to minimally symptomatic. Familial cases with different expressiveness were reported before. We herein report a 22-week terminated fetus, which was a product of a GIPO 16-year-old healthy mother. Initial ultrasound at 20 weeks gestation revealed severe oligohydramnios and a small fetus. Subsequent ultrasound revealed absent stomach, dysplastic kidneys, short limbs, distal dysplasia, abnormal facies and the possibility of Roberts syndrome was discussed. The patient was counseled and pregnancy termination was sought. Cytogenetic studies revealed a normal 46,XY male karyotype and negative study for centromere analysis. Autopsy revealed a normally grown 22-23 week male fetus with hypothalamic hamartoma, polydactyly, imperforate anus and multiple other congenital anomalies. He had small, wide-spaced eyes, bilateral choanal atresia, soft tissue mass of the philtrum, small mouth with soft tissue fusion between alveolar ridges, lips and tongue, abnormal palate with possible midline clefting, micrognathia and simple lowset ears. There were short upper extremity digits with hypoplastic nail bed and bilateral partial duplication and fusion of the fourth digits. The feel were markedly everted with small medially placed great toes. The third, fourth and fifth digits are all short with poor nail bed. All digits had prominent syndactyly. There was anal atresia with blind rectosigmoid colon emptying into the bladder region without rectovesicular fistula. There was bilateral renal hypoplastic dysplasia with disorganization of the cortex. Brain examination revealed hypothalamic hamartoblastoma, 1.0 × 1.5 × 1.0 cm. There was absent cerebellar vermis, absent corpus callosum, probable absent olfactory grooves and tracts and sella turica wilh no pituitary gland present. Small adrenal glands with disorganization of the adrenal cortex were also noted. Cardiac exam revealed malrotation of the great vessels and cardiomegaly. Pulmonary hypoplasia and oligohydramnios sequence was noted with flexion conlractures of the joints. Our patient represents an extreme spectrum of PHS and emphasizes the importance of recognition of fetal syndrome and documented autopsy for genetic counseling.