Novel SLC26A4 variant in Pendred syndrome with non-classical inheritance: a case report.

PURPOSE: To evaluate the clinical and diagnostic implications of identifying only a single heterozygous SLC26A4 variant in a patient with the full clinical phenotype of Pendred syndrome.

METHODS

A 20‑year‑old woman with lifelong deaf‑mutism developed progressive retrosternal goitre with dysphagia and dyspnoea. Pure-tone audiometry demonstrated profound bilateral sensorineural hearing loss. CT revealed nodular goitre and bilateral large vestibular aqueducts. She underwent thyroid lobectomy‑isthmectomy. Whole‑exome sequencing and quantitative PCR were performed on blood, excised thyroid tissue and parental samples.

RESULTS

Histology confirmed benign nodular goitre. Genomics detected a heterozygous 57‑kb exons 2-3 deletion in SLC26A4, inherited from an asymptomatic mother; no second pathogenic variant was identified. Family studies confirmed maternal inheritance and absence of the variant in the father. The patient remained euthyroid and symptom‑free six months post‑surgery.

CONCLUSIONS

A single heterozygous structural variant can manifest full PDS, underscoring the importance of copy‑number analysis and segregation studies when only one SLC26A4 allele appears affected.