Syndromic hearing loss

Syndromic hearing loss combines hearing impairment with extra-auditory malformations or systemic clinical findings. The hearing loss is most commonly sensorineural, and currently lists more than 660 entries for syndromic forms of sensorineural hearing loss. Phenotypes range from forms in which hearing loss is the predominant feature to multisystem disorders in which hearing impairment is one component among cardiac, ocular, renal, pigmentary, or thyroid manifestations. Age of onset is highly variable across the spectrum: , , , and Jervell and Lange-Nielsen syndromes typically present congenitally or in early childhood, whereas the sensorineural hearing loss of typically begins after age 10 years and the vestibular typically present at 18-24 years. Approximately 20% of children with apparently nonsyndromic hearing loss at initial presentation are subsequently diagnosed with a syndromic form, which underscores the importance of careful clinical reassessment over time.

The estimated prevalence of congenital bilateral hearing loss is approximately 1.33 per 1,000 newborns, based on European data. Approximately 80% of prelingual hearing loss is attributed to genetic causes, of which syndromic forms account for approximately 20%.

A large number of genes have been associated with syndromic hearing loss. Within the autosomal recessive group, (hearing loss with retinitis pigmentosa) is the most common syndromic form. Other frequently identified causes include (hearing loss with pigmentary anomalies), (hearing loss with thyroid goitre), and (hearing loss with progressive nephropathy).

The genetic conditions associated with syndromic hearing loss follow heterogeneous inheritance patterns. Autosomal recessive, autosomal dominant, X-linked, and mitochondrial modes of inheritance are all documented across the spectrum, with most mitochondrial-DNA-related hearing loss being syndromic and involving multisystem disorders. De novo pathogenic variants are recognised contributors in some autosomal dominant entities.

• Where syndromic hearing loss is suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

• Shearer AE, Hildebrand MS, Odell AM, Smith RJH. Genetic hearing loss overview. 2023 Apr 6. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: PMID:20301607.
• Hatzopoulos S, Cardinali L, Skarżyński PH, Zimatore G. The otoacoustic emissions in the universal neonatal hearing screening: an update on the European data (2004 to 2024). Children (Basel). 2024;11(11):1276. doi:10.3390/children11111276. PMID:; PMCID: PMC11592710.
• Verstappen G, Foulon I, Van den Houte K, Heuninck E, Van Overmeire B, Gordts F, et al. Analysis of congenital hearing loss after neonatal hearing screening. Front Pediatr. 2023;11:1153123. doi:10.3389/fped.2023.1153123. PMID:; PMCID: PMC10226668.