HDR syndrome: Large cohort and systematic review

Area of Science:

• Genetics
• Endocrinology
• Otolaryngology

Background:

• Hereditary hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant disorder.
• It is caused by heterozygous pathogenic variants in the GATA3 gene, with variable penetrance of associated conditions.
• Understanding the genotype-phenotype relationship is crucial for managing HDR syndrome.

Approach:

• The study analyzed 28 patients with HDR syndrome and conducted a comprehensive literature review.
• Pathogenic GATA3 variants were modeled to identify patterns in their location.
• Audiograms were analyzed to establish a typical audiometric profile for the condition.

Key Points:

• Hearing loss is a near-universal feature of HDR syndrome.
• Genital malformations and basal ganglia calcifications, initially considered rare, appear more prevalent.
• Missense GATA3 variants cluster near the Zinc Finger domains, suggesting a specific mechanism of action.

Conclusions:

• Early and regular hearing assessments are essential for patients with HDR syndrome.
• Monitoring parathyroid function and vesicoureteral reflux is vital for preventing complications.
• New pathogenic GATA3 variants were identified, some linked to specific clinical manifestations.