ESPE Abstracts

Introduction: Pallister-Hall syndrome (PHS) is a rare disease with autosomal dominant pattern of inheritance caused by CHD7 gene mutation and characterized by epiglottis malformation, polydactyly or oligodactyly, hypothalamic hamartoma and visceral abnormalities. Central precocious puberty is the most common endocrine abnormality detected in PHS. Regardless isolated growth hormone deficiency, pan hypopituitarism and genitourinary malformation are reported in PHS it is still not clear if they are secondary due to hamartoma or represent independent manifestations of hypothalamic-pituitary dysfunction.

Case report: patient S. was admitted to the Pediatric department of «Endocrinology Research Center» at the age of 3 with complains to precocious puberty and increased height velocity. Anamnesis revealed that from the day one after birth, the boy suffered from respiratory insufficiency. The malformation of the larynx and the right side of the bronchial tree was diagnosed, which required tracheostomy followed by several stages of reconstruction of the epiglottis and larynx. Also, hypoplasia of the right kidney, hypoplasia of the gallbladder, oligodactyly of both hands and syndactyly of 1 and 2 fingers of the feet were revealed. Due to intestinal obstruction in neonatal period cystic fibrosis was suspected. The diagnosis was confirmed by positive results of neonatal screening and genetic test (two heterozygous pathogenic variants in CFTR gene (NM 000492.4)). By physical examination: increased height velocity (height SDS: +2, 47), Tanner genital stage 3 (testicular volume 15 ml), advanced bone age (8,5 years by TW-20). GhRH stimulation test showed pubertal LH peak (25 u/L). MRI revealed a hypothalamic hamartoma. Given the presence of malformations of larynx and kidneys in combination with oligodactyly and hamartoma, which are not typical for cystic fibrosis, full exome sequencing was conducted. Heterozygous variant c.3454G>T: p.E1152X in GLI3 gene was detected.

Conclusion: the primary criterias for diagnosing PHS are hypothalamic hamartoma, oligodactyly or polydactyly and epiglottis malformation. Imperforate anus, renal malformations, congenital heart disease, growth hormone deficiency or hypopituitarism and genital hypoplasia are also common. Due to the autosomal-dominant type of inheritance, presence of pathogenic variant in GLI3 in combination with one of the diagnostic criteria is sufficient to confirm the PHS. It helps to diagnose patients with partial forms (sub-PHS) of disorder.