A 2-year-old child born to consanguineous parents presents with bilateral profound sensorineural hearing loss detected on newborn screening, delayed motor milestones (independent walking achieved only at 22 months), and recurrent falls with balance impairment that worsens in darkness. Ophthalmologic examination reveals bone-spicule pigmentation on fundus with attenuated retinal arterioles. The clinical and audiometric findings marked **A** in the diagram are most consistent with which genetic diagnosis?

Question

Accepted Answer

B. Usher Syndrome Type 1B (MYO7A mutation). ## Why Usher Syndrome Type 1B (MYO7A mutation) is right

The clinical triad of **bilateral profound congenital sensorineural hearing loss, vestibular areflexia (manifested as delayed motor milestones and independent walking ≥18 months), and retinitis pigmentosa (bone-spicule pigmentation, attenuated arterioles)** is pathognomonic for Usher Syndrome Type 1. MYO7A encodes myosin VIIA, a motor protein critical for stereocilia bundle stability and opsin trafficking in photoreceptors. It is the most common gene responsible for USH1B and accounts for the characteristic phenotype marked **A** in the diagram. Usher Type 1 is the most severe form and the most common cause of combined congenital deafness and blindness (~50% of deaf-blind individuals), with prevalence of 3–6/100,000 (Cummings Otolaryngology 7e; Smith RJH GeneReviews 2023).

## Why each distractor is wrong

- **Usher Syndrome Type 2A (USH2A mutation)**: USH2 presents with congenital moderate-to-severe SNHL (often better at low frequencies) and NORMAL vestibular function—no vestibular areflexia, no delayed motor milestones. RP onset is in the 2nd decade, not early childhood. This patient's profound hearing loss and vestibular dysfunction rule out Type 2.

- **Pendred Syndrome (SLC26A4 mutation)**: Pendred causes bilateral SNHL with thyroid goiter and enlarged vestibular aqueduct (EVA) on imaging. It does NOT cause retinitis pigmentosa or vestibular areflexia. The presence of RP and balance impairment excludes this diagnosis.

- **Connexin-26 related deafness (GJB2 mutation)**: GJB2 mutations cause nonsyndromic profound flat SNHL (marked **D** in the diagram). There is no associated retinitis pigmentosa, vestibular dysfunction, or progressive vision loss. This is a purely auditory phenotype.

**High-Yield:** Usher Type 1 = profound congenital SNHL + vestibular areflexia (delayed walking) + early-onset RP; MYO7A is the most common USH1 gene and the anchor for diagnosis in this clinical presentation.

[cite: Cummings Otolaryngology 7e; Smith RJH GeneReviews — Usher Syndrome Type 1 2023]

Answer

A. Usher Syndrome Type 2A (USH2A mutation)

Answer

C. Connexin-26 related deafness (GJB2 mutation)

Answer

D. Pendred Syndrome (SLC26A4 mutation)

Explanation

Why Usher Syndrome Type 1B (MYO7A mutation) is right

Why each distractor is wrong

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