Genetic deafness and blindness syndromes — formative SAQs

Question 1 (10 marks)

A newborn boy fails his universal hearing screen on both ears at day 3 and again at day 10. Diagnostic auditory brainstem response testing at six weeks confirms bilateral severe sensorineural hearing loss. His physical examination is entirely normal. There is no family history of hearing loss and no consanguinity. (a) Outline your initial aetiological workup. (b) Given negative GJB2 and CMV PCR with bilateral enlarged vestibular aqueducts, name the diagnosis and further workup. (c) State the recurrence risk and reproductive options. ^{[1] [2]}

Model answer

(a) The workup confirms the hearing loss with diagnostic ABR and OAE, then pursues the aetiology in a tiered sequence. CMV PCR on saliva or urine within the first three weeks of life excludes congenital cytomegalovirus, the most common non-genetic cause and a treatable one if identified early. An ECG is non-negotiable to exclude Jervell and Lange-Nielsen syndrome with its prolonged QT and sudden-death risk. GJB2 sequencing is the highest-yield single genetic test for congenital nonsyndromic sensorineural hearing loss. Temporal bone CT or MRI looks for enlarged vestibular aqueduct or cochlear malformation. A three-generation pedigree and parental examination complete the initial assessment. ^{[2] [7]}

(b) With negative GJB2 and CMV PCR but bilateral enlarged vestibular aqueducts on imaging, the diagnosis is Pendred syndrome caused by SLC26A4 variants affecting the pendrin transporter. The further workup includes SLC26A4 sequencing, thyroid function tests, and thyroid ultrasound, recognising that the goitre may be absent in childhood and biochemically euthyroid. The family is counselled that Pendred is autosomal recessive with variable expressivity, and that minor head trauma can worsen the hearing loss. ^[5]

(c) The recurrence risk for a confirmed autosomal-recessive condition is 25 per cent for each subsequent pregnancy. Reproductive options include prenatal diagnosis by chorionic villus sampling or amniocentesis with targeted SLC26A4 testing, and preimplantation genetic testing with in-vitro fertilisation. Cascade testing of first-degree relatives identifies carrier status and enables informed reproductive decisions. ^[1]