Xia-Gibbs Syndrome

Excerpt

Clinical characteristics: The main features of Xia-Gibbs syndrome (XGS), present in a majority of affected individuals, include delayed motor milestones, speech delay with severely limited or absent speech, moderate-to-severe cognitive impairment, hypotonia, structural brain anomalies, and nonspecific dysmorphic features. Other features may include sleep apnea, movement disorders (ataxia, tremors, and bradykinesias) that often become apparent in childhood or adolescence, short stature, seizures, eye anomalies, behavioral concerns, autism spectrum disorder, scoliosis, and laryngomalacia.

Diagnosis/testing: The diagnosis of XGS is established in a proband with suggestive clinical findings and a heterozygous pathogenic variant in AHDC1 that is predicted to lead to a truncated protein, identified by molecular genetic testing

Management: Treatment of manifestations: Treatment is symptomatic and can include: speech, occupational, and physical therapy; specialized educational programs depending on individual needs; standard treatment of behavioral concerns (ADHD, anxiety) and autism spectrum disorders; treatment of movement disorders by a neurologist familiar with movement disorders; standard treatment of seizures, feeding difficulties, gastroesophageal reflux disease, obstructive sleep apnea; stridor/disordered breathing, scoliosis, ophthalmologic/vision issues, and hearing loss; consideration of growth hormone therapy in those with short stature who also have growth hormone deficiency.

Surveillance: At each visit monitor growth and nutrition, occupational and physical therapy needs; assess for seizures, movement disorders, developmental progress, behavioral issues, gastrointestinal issues, respiratory issues, and family needs. Clinical assessment for scoliosis at each visit in childhood until skeletal maturity. Annual vision and hearing assessments. Measurement of growth hormone level in those with poor growth velocity.

Genetic counseling: XGS is an autosomal dominant disorder typically caused by a de novo pathogenic truncating variant in AHDC1. The risk to other family members is presumed to be low, but parental testing should be done when possible to confirm that the variant is de novo. Once an AHDC1 pathogenic variant has been identified in an affected family member, prenatal testing and preimplantation genetic testing are possible.