Newly recognized recessive syndrome characterized by dysmorphic features, hypogonadotropic hypogonadism, severe microcephaly, and sensorineural hearing loss maps to 3p21.3

Abstract

We present a newly recognized, likely autosomal recessive, pleiotropic disorder seen in four individuals (three siblings and their nephew) from a consanguineous family of Pakistani origin. The condition is characterized by hypogonadotropic hypogonadism, severe microcephaly, sensorineural deafness, moderate learning disability, and distinctive facial dysmorphic features. Autozygosity mapping using SNP array genotyping defined a single, large autozygous region of 13.1 Mb on chromosome 3p21 common to the affected individuals. The critical region contains 227 genes and initial sequence analysis of a functional candidate gene has not identified causative mutations.

Perspectives in Pediatric Pathology, Chapter 18. Hypogonadotropic Hypogonadisms. Pediatric and Pubertal Presentations

“…Hypogonadotropic hypogonadism also has been observed in the following syndromes: Carpenter, Biemond, and Fraser syndromes. Hypogonadotropic hypogonadism also can be associated with congenital adrenal hypoplasia, Moebius syndrome, POEMS syndrome, congenital nonprogressive myopathy due to multicore disease, hypotonia–cystinuria syndrome, MEHMO syndrome, mitochondrial progressive external ophthalmoplegia, mitochondrial 10-DNA depletion syndrome 7, microcephaly, bilateral sensorineural hearing loss and facial dysmorphic features [254,255].…”