Syndromic Intellectual Disability Caused by a Novel Truncating Variant in AHDC1: A Case Report

Abstract

Mutations in the AHDC1 gene are associated with the Xia-Gibbs syndrome (XGS), a sporadic genetic disorder characterised by developmental delay, intellectual disability, hypotonia, obstructive sleep apnoea, dysmorphic facial features, and cerebral malformations with plagiocephaly. Here we report the case of a 13-year-old Colombian female patient with a history of developmental delay, speech delay, sleep disturbances, and dysmorphic craniofacial features. The whole exome sequencing (WES) test revealed a novel de novo heterozygous frameshift mutation in AHDC1. The present case report describes the second case of mutations in AHDC1 in a Latin American patient. A literature review showed that the clinical features were similar in all reported patients. The WES test enabled the identification of the causality of this disorder characterised by high clinical and genetic heterogeneity.

Keywords: Frameshift mutations; Whole exome sequencing; Developmental disabilities.

Figure1

Facial features of the patient included a broad forehead, horizontal eyebrows, small and low-set ears, mild ptosis, proptosis; upslanting palpebral fissures, mild facial hypoplasia, flat nasal bridge, nasal root depression; and an acute nasal angle, long philtrum, thin upper lip, and micrognathia.

Figure2

Pedigree information of the patient and Sanger sequencing electropherogram of both the patient and her parents. The pedigree is consistent with a de novo frameshift mutation.

Figure3

Wildtype AHDC1 gene structure (A) and mutated AHDC1 gene suggested structure (B). The region of frameshift mutation in ADHC1 protein is shown (yellow ray: The mutation site, light colour: The region and domain lost due to the stop codon generated by frameshift mutation).