A new FOXE1 homozygous frameshift variant expands the genotypic and phenotypic spectrum of Bamforth-Lazarus syndrome.

ABSTRACT

Bamforth-Lazarus syndrome is a rare autosomal recessive disease caused by biallelic loss-of-function variants in the FOXE1 gene. The condition is characterized by congenital hypothyroidism due to thyroid agenesis or thyroid hypoplasia, cleft palate, spiky hair, with or without choanal atresia, and bifid epiglottis. To date, seven pathogenic variants have been reported in the FOXE1 gene causing Bamforth-Lazarus syndrome. Here we report a novel homozygous loss-of-function variant in the FOXE1 gene NM_004473.4c.141dupCp.(Leu49Profs*75) leading to congenital hypothyroidism due to thyroid agenesis, scalp hair abnormalities, cleft palate, small areola, cafe-au-lait spots, mild bilateral hearing loss, skin abnormalities, and facial dysmorphism. We describe the evolving phenotype in the patient with age and review previous variants reported in FOXE1. This report further expands the clinical and molecular spectrum of Bamforth-Lazarus syndrome.