Abstract
INTRODUCTION: Xia-Gibbs syndrome (XGS) is a rare syndromic disorder characterized by developmental delay with intellectual disability, muscular hypotonia, brain anomalies, and nonspecific dysmorphic features. Different heterozygous variants in AHDC1 have been reported as causal for XGS, comprising mainly de novo stop-gain and frameshift events, but also missense variants, deletions, and a duplication of the locus. CASE PRESENTATION: We hereby report 2 patients with clinical features of XGS. In the first patient, a de novo interstitial deletion in 1p36.11p35.3 encompassing the entire coding region of AHDC1 was initially suspected by trio exome sequencing and subsequently confirmed by shallow genome sequencing. In the second patient, a de novo deletion comprising most of the 5' untranslated region of AHDC1 was detected by genome sequencing. CONCLUSION: We identified the smallest deletion comprising AHDC1 reported so far by shallow genome sequencing as well as another small AHDC1 deletion by genome sequencing. These methods represent useful techniques for the identification and confirmation of small deletions and structural variants. Furthermore, our data provide additional evidence of AHDC1 haploinsufficiency as a disease mechanism in XGS. Clinically, foot deformity, skin and connective tissue abnormalities observed in one of the patients are consistent with other reported cases of XGS. These findings suggest that these manifestations could be considered as more prevalent characteristics, underscoring the importance of in-depth phenotyping.