Trichohepatoneurodevelopmental Syndrome

A number sign (#) is used with this entry because of evidence that trichohepatoneurodevelopmental syndrome (THNS) is caused by homozygous or compound heterozygous mutation in the CCDC47 gene (618260) on chromosome 17q23.

Description

Trichohepatoneurodevelopmental syndrome is a complex multisystem disorder characterized by woolly or coarse hair, liver dysfunction, pruritus, dysmorphic features, hypotonia, and severe global developmental delay (Morimoto et al., 2018).

Clinical Features

Morimoto et al. (2018) reported 4 unrelated children with a complex multisystem disorder. All 4 probands exhibited dysmorphic facial features, with coarse facies, ptosis, downturned mouth, and simple ears, as well as unusual hair that was coarse and/or woolly and/or curly. Other features present in all included microcephaly, brachycephaly, severe global developmental delay, liver dysfunction, pruritus, hypotonia, joint laxity or distal arthrogryposis, nipple hypoplasia, and overlapping toes. Most probands also showed midface hypoplasia, hypertelorism, dental abnormalities, plagiocephaly, narrow chest, hip dysplasia, and bilateral clubfoot. The patients also exhibited severe developmental delay and were nonverbal with generalized hypotonia at 5 to 8 years of age; neuroimaging revealed cerebral atrophy in all 4 patients, with abnormal ventricular morphology in 3 of them. Two of the patients were immunodeficient and experienced recurrent infections.

Molecular Genetics

In 4 unrelated children with woolly hair, liver dysfunction, pruritus, dysmorphic features, and developmental delay, Morimoto et al. (2018) performed whole-exome sequencing and identified homozygosity or compound heterozygosity for mutations in the CCDC47 gene (618260.0001-618260.0004).