Xia-Gibbs syndrome

chromosome 1

Xia-Gibbs syndrome (XGS) is a rare disorder manifested by intellectual disability, speech delay, hypotonia, scoliosis, delayed brain myelination, and a large cisterna magna. In most cases XGS is caused by mutations in the AHDC1 gene, located at 1p36.11p35.3. Bertrand et al. presented two patients with XGS who had small deletions of the 1p36.11p35.3 segment involving the AHDC1 gene. The first patient was a 14-year-old male presenting with intellectual disability, dysmorphic features, pes cavus, and progressive scoliosis. As a baby, he was noted to have sucking weakness, muscular hypotonia, developmental delay, and an inguinal hernia (4 months old). Later he revealed delayed cerebral myelination, vision deficit and strabismus, joint hypermobility, luxation of the elbow and patella, an elongated and asymmetrical face, coarse facial features, large protruding ears, a long philtrum, prominent incisors, sparse body hair, soft and excessive palmar skin, and a stellate pattern of the iris. At 14, his brain MRI revealed a mega cisterna magna.  Genetic examination identified a de novo 17 kb interstitial heterozygous deletion at 1p36.11 to 1p35.3. The second patient was ten years old and presented with global development delay, scoliosis, and hypotonia. Between the patient’s first three to six months of life, he displayed hypotonia, global developmental delay, and macrocephaly. At 7 months, increased cerebral spinal fluid, a thin corpus callosum, mild cerebellar hypoplasia, mild ventricular enlargement, enlarged cisterna magna, and deep white matter volume loss were found on an MRI. Through the first 4.5 years of life, his head circumference was documented to be greater than the 99^th percentile. Exome sequencing and chromosomal microarray analysis were ordered and returned negative results. Trio genome sequencing was ordered, and a 58kb de novo deletion in the AHDC1 gene was reported. These two patients had small de novo heterozygous deletions in the AHDC1 gene and shared a few common symptoms of XGS. The authors showed that small deletions in 1p36.11-p35.3 should be considered as a possible cause of this disorder.

Bertrand M. et al. “De novo AHDC1 deletions identified by genome sequencing in two individuals with Xia-Gibbs syndrome”. “Molecular Syndromology”, 2024, 15(5), 389–397.