Hypertrichosis, hyperkeratosis, abnormal corpus callosum, mental retardation and dysmorphic features in three unrelated females

Abstract

We report three unrelated patients with hypertrichosis, mild to moderate mental retardation, and dysmorphic facial features including low anterior hairline, thick arched eyebrows, nose with broad tip and columella below alae nasi, short philtrum, thick drooping lower lip and simple posteriorly rotated ears. They also had rough skin with hyperkeratotic plaques. Feet and finger tips were broad. All of them had personality problems like aggressiveness, stubborn temperament or tendency to withdraw. Brain MRI showed thick and short corpus callosum. We believe that these patients represent a new syndrome of unknown aetiology.

Thick Corpus Callosum in Children

“…Contrary to most reports in the literature that claim that a TCC usually involves a grave prognosis, mental retardation, and/or serious developmental delay,202123 our results consistently excluded its specific association with a serious prognosis. Of course, the prognosis in an individual patient is dependent upon the underlying condition with which the thick CC was described, and one cannot infer from our cases that a TCC is a prognosis-determining feature.…”

The HHID syndrome of hypertrichosis, hyperkeratosis, abnormal corpus callosum, intellectual disability, and minor anomalies is caused by mutations in ARID1B

“…In 2004, Pöyhönen et al reported on three unrelated patients with hypertrichosis, hyperkeratosis, abnormal corpus callosum, intellectual disability (ID), and minor anomalies including low anterior hairline, thick arched eyebrows, broad nasal tip, columella below alae nasi, short philtrum, thick‐everted lower lip, simple posteriorly angulated ears, and broad feet and finger tips (Pöyhönen et al, 2004). This observation was recognized as an OMIM entity (OMIM 609943), hereafter referred to as HHID syndrome.…”

“…No further individual with suspected HHID has been published and the cause of their condition remained elusive. We now used whole exome sequencing (WES) in the three patients published by Pöyhönen et al (2004) and discuss the updated phenotype in the light of today's clinical knowledge and our genetic findings.…”

“…The detailed initial clinical description of patient 1 (P1, at age of 16 years), patient 2 (P2, at age of 17 years), and patient 3 (P3, at age of 10 years), all born to non‐consanguineous parents from different parts of Finland, is provided in the original article by Pöyhönen et al (2004). Clinical reassessment of the three patients after about 10 years revealed the previously described phenotype, except for hypertrichosis, which now resembled normal variation.…”

“…However, our patients show only mildly diminished nail size and demonstrate that the key feature of hypertrichosis vanishes to levels of normal variation during adolescence. Moreover, the most distinctive feature shared by all patients with suspected HHID (Dalal & Mehrotra, 2009; Pöyhönen et al, 2004) is the ectodermal sign of hyperkeratotic plaques which has not yet been reported in any patient with CSS or ARID1B ‐associated nonspecific ID. This might therefore constitute either an underreported or an infrequent but distinct novel feature of ARID1B ‐associated phenotypes.…”