Two Chinese Xia‐Gibbs syndrome patients with partial growth hormone deficiency

Abstract

Background Heterozygous mutations in the AT‐hook DNA‐binding motif containing one (AHDC1, OMIM * 615790) gene cause an autosomal dominant multisystem developmental disorder known as Xia‐Gibbs syndrome (OMIM #615829). Xia‐Gibbs syndrome typically presented with global developmental delay, hypotonia, obstructive sleep apnea, seizures, delayed myelination, micrognathia, and other mild dysmorphic features. Methods Description of the clinical materials of two Chinese boys who were diagnosed with Xia‐Gibbs syndrome based on clinical presentations and next generation sequencing. Review of clinical features and AHDC1 mutations in previously reported Xia‐Gibbs syndrome patients together with our two new patients. Results The Xia‐Gibbs syndrome patients exhibited short stature, hypotonia, global developmental delay, speech delay, simian crease, and mild dysmorphic features. Next generation sequencing revealed de novo heterozygous variants in AHDC1 gene. In addition, laboratory test revealed partial growth hormone deficiency. Both patients underwent growth hormone replacement therapy for 24 and 9 months, respectively, and exhibited good response to the treatment. Conclusion This is the first report of Xia‐Gibbs syndrome patients to be treated with growth hormone. Review of previously reported Xia‐Gibbs syndrome patient indicated that short stature is a frequent feature of this condition, but its underlying cause needs to be further investigated.

Focusing on Autism Spectrum Disorder in Xia–Gibbs Syndrome: Description of a Female with High Functioning Autism and Literature Review

“…Based on the current systematic review of the literature, neuroimaging abnormalities are detected in the majority of patients, without preferential brain localization. The most frequent findings include thinning of the corpus callosum [2,4,15,26,27,30,[48][49][50], posterior fossa anomalies [4,15,27,30,51], cerebral atrophy [26,31,39,40,49,51,52], white matter anomalies [2,30], and cortical malformation/dysmorphism [15]. Previous studies frequently observed a reduction of CC volume in subjects with ASD (see [53] for a review) as well as a correlation between decreased CC volume and severity of ASD features, supporting the hypothesis of impaired interhemispheric connectivity in ASD [54].…”

Xia-Gibbs Syndrome: A Review of Literature

“…No side effects of the treatment were noticed during the study. This study demonstrated the beneficial effect of replacing growth hormone in patients with XGS [ 38 ]. Nonetheless, further evaluation into the matter is required to understand the long-term effects as well as the consistency of the effect of this treatment.…”

“…Cheng et al (2019) reported two cases from China who presented with short stature. On endocrinological work-up, they were found to be deficient in growth hormone [ 38 ]. Before the confirmatory genetic testing, growth hormone was used therapeutically.…”

Clinical presentation and evolution of Xia‐Gibbs syndrome due to p.Gly375ArgfsTer3 variant in a patient from DR Congo (Central Africa)

“…Xia‐Gibbs syndrome (XGS: OMIM # 615829) is a very rare genetic condition reported for the first time in 2014 (Xia et al, 2014). Manifestations include developmental delay and intellectual disability (DD/ID), behavior problems, hypotonia at birth, and brain anomalies (Cheng et al, 2019; Diaz‐Ordonez, Ramirez‐Montano, Candelo, Cruz, & Pachajoa, 2019; Gumus, 2020; Jiang et al, 2018; Wang et al, 2020). Speech is delayed, limited or absent.…”