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Purpose <p>Harboyan syndrome is a rare autosomal recessive condition comprised of congenital hereditary endothelial dystrophy (CHED) and progressive, bilateral sensorineural hearing loss (SNHL) with a typical onset of 10–25&#xa0;years of age. Homozygous or compound heterozygous pathogenic variants in <i>SLC4A11</i> cause corneal edema due to increased sodium chloride concentrations and morphologic changes in inner ear fibrocytes leading to CHED and SNHL, respectively. We present a 4-year-old patient, now 10&#xa0;years old, with CHED and early-onset SNHL, whose clinical diagnosis of Harboyan syndrome was confirmed via molecular testing.</p> Methods <p>Next-generation sequencing (NGS) panels of genes responsible for hearing loss and congenital glaucoma were performed on the patient’s peripheral blood. Follow-up included evaluation by geneticists, ophthalmologists, audiologists, and otolaryngologists, and routine literature reviews for updates on variants of uncertain significance (VUS) reclassification.</p> Results <p>Initial results revealed two candidate genes: <i>SLC4A11</i> and <i>ADGRV1</i>. Novel <i>SLC4A11</i> variants were identified: c.623del (p.Val208Glyfs*14) classified as pathogenic and c.2606 + 1G &gt; A (maternal) classified as VUS. This <i>SLC4A11</i> VUS was later reclassified to pathogenic, confirming the diagnosis.</p> Conclusions <p>This case report describes a pediatric patient with deafness and blindness whose clinical diagnosis of Harboyan syndrome was confirmed via genotype–phenotype correlations. We recommend patients with multi-sensory disorders be evaluated in a multidisciplinary setting with access to molecular testing so genotype–phenotype correlations may be identified swiftly along with providing anticipatory guidance.</p>

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Diagnosing Harboyan syndrome in a patient with multiple variants of uncertain significance (VUS)

  • 期刊论文

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  • 发表日期：

    2025年7月16日

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  • Sloane Clay,
  • Adele K. Evans,
  • Regina Zambrano,
  • Luc Courtois,
  • Lena Al-Dujaili,
  • Belinda Mantle,
  • Fern Tsien

摘要

Purpose

Harboyan syndrome is a rare autosomal recessive condition comprised of congenital hereditary endothelial dystrophy (CHED) and progressive, bilateral sensorineural hearing loss (SNHL) with a typical onset of 10–25 years of age. Homozygous or compound heterozygous pathogenic variants in SLC4A11 cause corneal edema due to increased sodium chloride concentrations and morphologic changes in inner ear fibrocytes leading to CHED and SNHL, respectively. We present a 4-year-old patient, now 10 years old, with CHED and early-onset SNHL, whose clinical diagnosis of Harboyan syndrome was confirmed via molecular testing.

Methods

Next-generation sequencing (NGS) panels of genes responsible for hearing loss and congenital glaucoma were performed on the patient’s peripheral blood. Follow-up included evaluation by geneticists, ophthalmologists, audiologists, and otolaryngologists, and routine literature reviews for updates on variants of uncertain significance (VUS) reclassification.

Results

Initial results revealed two candidate genes: SLC4A11 and ADGRV1. Novel SLC4A11 variants were identified: c.623del (p.Val208Glyfs*14) classified as pathogenic and c.2606 + 1G > A (maternal) classified as VUS. This SLC4A11 VUS was later reclassified to pathogenic, confirming the diagnosis.

Conclusions

This case report describes a pediatric patient with deafness and blindness whose clinical diagnosis of Harboyan syndrome was confirmed via genotype–phenotype correlations. We recommend patients with multi-sensory disorders be evaluated in a multidisciplinary setting with access to molecular testing so genotype–phenotype correlations may be identified swiftly along with providing anticipatory guidance.