Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly—a new syndrome? Part I: Clinical, causal, and pathogenetic considerations

TLDR

The study reports six neonates with a lethal malformation syndrome characterized by hypothalamic hamartoblastoma, postaxial polydactyly, and imperforate anus. The infants exhibited a spectrum of anomalies—including laryngeal cleft, abnormal lung lobulation, renal dysplasia, short fourth metacarpals, nail dysplasia, multiple buccal frenula, hypoadrenalism, microphallus, congenital heart defects, and intrauterine growth retardation—alongside hypopituitarism, with all cases sporadic, normal karyotypes, unremarkable family histories, and no common exposures, suggesting a previously unreported syndrome of unknown etiology.

Abstract

Abstract We report on six infants with a neonatally lethal malformation syndrome of hypothalamic hamartoblastoma, postaxial polydactyly, and imperforate anus. Some, but not all, patients had laryngeal cleft, abnormal lung lobulation, renal agenesis and/or renal dysplasia, short 4th metacarpals, nail dysplasia, multiple buccal frenula, hypoadrenalism, microphallus, congential heart defect, and intrauterine growth retardation. The infants also had hypopituitarism and hypoadrenalism. All were sporadic cases, parents were not consanguineous, chromosomes were apparently normal. Family histories were unremarkable. There was insecticide and/or herbicide exposure in several of the cases, but no exposures were common to all 6 mothers. Five of the patients were born within an 8‐month period, but all in different geographic locations. It is postulated that this is a previously apparently unreported syndrome of presently unknown cause.