Hypogonadotropic Hypogonadism and Kleefstra Syndrome due to a Pathogenic Variant in the EHMT1 Gene: An Underrecognized Association

Abstract

Kleefstra syndrome is a genetic condition characterized by intellectual disability, childhood hypotonia, and facial dysmorphisms. Genital anomalies such as micropenis, cryptorchidism, and hypospadias have been reported in 30-40% of males diagnosed with the disease. However, endocrinological investigations have been limited. We describe a case of an adolescent male with Kleefstra syndrome due to a pathogenic variant in the EHMT1 gene whose workup for isolated micropenis is suggestive of a partial hypogonadotropic hypogonadism. A possible endocrine mechanism of the genital anomaly associated with Kleefstra syndrome is discussed.