Severe congenital hearing loss due to a homozygous SLC26A4 splice variant

We present the case of a 6-year-old boy diagnosed with bilateral severe-to-profound sensorineural hearing loss, first identified during routine early childhood screening, accompanied by muscular hypotonia and a combined specific developmental disorder affecting speech, fine motor skills, and cognition. Standardized developmental testing demonstrated nonverbal intellectual abilities in the range of learning disability. The patient is fitted with bilateral hearing aids. Additional findings included poor dental health with multiple crowns.
Family history was notable for parental consanguinity (first cousins). A maternal uncle reportedly became blind early in life and died in his thirties, and second-degree cousins were said to have experienced hearing impairment.
Trio exome sequencing revealed a homozygous pathogenic splice variant in SLC26A4 (NM_000441.2:c.164+1del), consistent with autosomal-recessive Pendred syndrome (PDS, OMIM #274600) or non-syndromic hearing loss with enlarged vestibular aqueduct (NSRD4/NSEVA, OMIM #600791).
The SLC26A4 gene encodes pendrin, an anion transporter highly expressed in the inner ear and thyroid. The phenotype associated with biallelic pathogenic variants typically includes congenital sensorineural hearing loss, vestibular dysfunction, and thyroid enlargement developing later in childhood or adolescence. Developmental delay, however, has not been commonly described in association with SLC26A4-related disease. In this patient, the combined specific developmental disorder appears to extend beyond the delay expected as a consequence of severe hearing impairment.
In summary, this case illustrates a common genetic etiology for congenital hearing loss in a consanguineous family, but also presents developmental features unusual for SLC26A4-associated disease. This highlights the importance of ongoing clinical follow-up and potential future re-analysis of genetic data.