New Case of XIA-GIBBS Syndrome with Atypical Phenotype

Abstract

Introduction: XIA-GIBBS Syndrome (XGS) has an incidence of less than 1 in 1,000,000 live births. Mutations in the AHDC1 gene result in global developmental delay, speech delay, hypotonia, dysmorphic facial features, and structural brain abnormalities.

Objective: To describe a case of XGS.

Methods: An 8-year-old male, the third child of non-consanguineous parents, with no family history of the condition. He was born at 40 weeks of gestation. Developmental milestones included sitting at 24 months, walking at 3 years, bisyllabic speech at 4 years, inadequate school performance for his age, and limited interaction with his environment. Brain MRI showed central and cortical exvacuous changes, thinning of the corpus callosum, and a 23 mm arachnoid cyst in the right retrovermian parasagittal region. Skeletal survey was normal. Physical examination revealed a height of 116 cm (-2.33 SD), weight of 25.6 kg (-0.25 SD), head circumference of 52 cm, right-sided facial asymmetry, downward-slanting palpebral fissures, severely decayed and misshapen teeth, unfolded ears with helical hypoplasia, short crus, normal palate, Grade II mitral ejection murmur in the chest, bilateral simian crease, short hands, short feet, clinodactyly, non-verbal, hypotonia, global developmental delay, and thick skin.

Results: The karyotype was normal 46 XY [25], genomic hybridization was negative, and clinical exome sequencing revealed a heterozygous mutation in the AHDC1 gene, specifically a variant of c.2082C>T p.Arg688Ter, classified as pathogenic.

Conclusions: The heterogeneous spectrum of XGS requires regular interdisciplinary follow-up and evaluations to improve the quality of life for patients.