STRC-Related Autosomal Recessive Hearing Loss

Clinical characteristics: STRC-related autosomal recessive hearing loss (STRC-HL) comprises both nonsyndromic sensorineural hearing loss and sensorineural hearing loss with decreased fertility in males who have biallelic contiguous gene deletions involving STRC and CATSPER2. The hearing loss is mild to moderate, congenital, bilateral, and symmetric. Mean pure tone hearing loss averages 40-50 decibels (dB) at the time of diagnosis; hearing loss is not severe to profound in children or young adults. Of note, while many newborns with STRC-HL will be identified by newborn hearing screening (NBHS), some newborns with STRC-HL will not because some screening methods may not detect milder hearing loss.

Males with biallelic contiguous gene deletions involving STRC and CATSPER2 are at risk for CATSPER2-related male infertility due to morphologic sperm abnormalities that affect sperm motility. In contrast, females with contiguous gene deletions do not have related fertility issues.

Diagnosis/testing: The diagnosis of STRC-HL is established in a proband with suggestive findings who has ONE of the following identified by molecular genetic testing: (1) biallelic STRC pathogenic variants; (2) one STRC pathogenic variant and one contiguous gene deletion involving STRC and CATSPER2; or (3) biallelic contiguous gene deletions involving STRC and CATSPER2.

Management: Treatment of manifestations: Multidisciplinary supportive treatment for hearing loss that includes an otolaryngologist with expertise in the management of early childhood otologic disorders, an audiologist experienced in the assessment of hearing loss in children, a speech-language pathologist, a clinical geneticist, a genetic counselor, and a pediatrician is recommended. Hearing aids (i.e., sound amplification), customized by an audiologist to the degree and frequency of hearing loss, may be recommended for individuals who have mild-to-moderate hearing loss.

When males with biallelic contiguous gene deletions involving STRC and CATSPER2 reach reproductive age, consultation with a reproductive specialist/endocrinologist for consideration of fertility-related evaluations is appropriate.

Surveillance: To monitor the degree of hearing loss, the individual's response to use of hearing aids, and development of speech and language, the following are recommended: (1) annual examination by an otolaryngologist familiar with genetic hearing loss to evaluate overall ear health; (2) repeat audiometry to identify any change in hearing, typically (a) every three months between birth and age two years, (b) every six months between ages two and five years, and (c) annually in children age five years and older if hearing is stable and there are no other otologic concerns; and (3) evaluation of speech/language/communication needs as recommended by a speech-language pathologist.

Agents/circumstances to avoid: Prolonged noise exposure exceeding 85 dB, including loud noise exposure from headphones and earbuds. Note that a headphone safety feature built into most smartphones can be set to limit the noise level.

Evaluation of relatives at risk: It is appropriate to clarify the genetic status of sibs of a proband with STRC-HL; early identification of infants and children with hearing loss allows appropriate support and management to be provided to the child and family.

Genetic counseling: STRC-HL is inherited in an autosomal recessive manner. The parents of an individual with STRC-HL are typically heterozygous for a genetic alteration involving STRC (i.e., a STRC pathogenic variant or a contiguous gene deletion involving STRC and CATSPER2). If both parents are known to be heterozygous for a genetic alteration involving STRC, each sib of the proband has at conception a 25% chance of having STRC-HL, a 50% chance of being a carrier and not having STRC-HL, and a 25% chance of not being a carrier and not having STRC-HL. Males with biallelic contiguous gene deletions involving STRC and CATSPER2 are at risk of decreased fertility due to abnormal sperm motility; thus, when they reach reproductive age they may benefit from fertility counseling and discussion of assistive reproductive technology options. Once the genetic alterations involving STRC have been identified in a family member with STRC-HL, prenatal and preimplantation genetic testing are possible.