A 12-year-old girl presents with progressive bilateral hearing loss detected on routine audiometry. The audiogram shows the pattern marked **B** in the diagram — high-frequency sensorineural loss. On examination, she has midface flattening with malar hypoplasia, a high-arched palate, and significant myopia (−8 D). Ophthalmologic evaluation reveals a characteristic membranous vitreous anomaly and early cataracts. Which genetic mutation is most likely responsible for this clinical presentation?
A. COL11A1 (Type 2 Stickler)
B. GJB2 on chromosome 13q12 (Connexin 26)
C. COL9A1 (Autosomal recessive Stickler)
D. COL2A1 on chromosome 12q13 (Type 1 Stickler)
Explanation
Why COL2A1 on chromosome 12q13 (Type 1 Stickler) is right
Stickler syndrome is an autosomal dominant collagenopathy, and Type 1 Stickler (caused by heterozygous COL2A1 mutations on chromosome 12q13) is the most common form, accounting for the majority of cases. The clinical presentation in this case—bilateral symmetric high-frequency sensorineural hearing loss (the pattern marked B), combined with the characteristic "MAR" phenotype (midface flattening/malar hypoplasia, high-arched palate, and arthropathy features), plus sight-threatening ocular manifestations (membranous vitreous anomaly, high myopia, early cataracts)—is pathognomonic for Type 1 Stickler. Defective type II collagen fibrillogenesis disrupts the structural integrity of the inner-ear basement membranes, vitreous body, and cartilage, producing this exact constellation of findings (Cummings Otolaryngology 7e; Glasscock-Shambaugh 7e).
Why each distractor is wrong
COL11A1 (Type 2 Stickler): While Type 2 Stickler also causes high-frequency SNHL and systemic features, COL11A1 mutations are responsible for a minority of cases and are less commonly encountered than COL2A1. Type 2 is not the most likely diagnosis when COL2A1 is available.
COL9A1 (Autosomal recessive Stickler): Autosomal recessive forms of Stickler syndrome are rare and caused by mutations in COL9A1 or COL9A2. The patient's presentation is consistent with autosomal dominant inheritance (no family history of consanguinity implied), making this unlikely.
GJB2 on chromosome 13q12 (Connexin 26): GJB2 mutations cause nonsyndromic sensorineural hearing loss (DFNB1/DFNA3), not syndromic hearing loss with the characteristic craniofacial, ocular, and skeletal features of Stickler syndrome. This is a common distractor for SNHL questions but does not explain the systemic phenotype.
High-YieldNEET PG
Type 1 Stickler (COL2A1, chromosome 12q13) is the most common form of Stickler syndrome and presents with bilateral high-frequency SNHL, the characteristic "flat" Stickler facies, high myopia, and a markedly elevated risk of retinal detachment in childhood/adolescence.
Cummings Otolaryngology 7e; Glasscock-Shambaugh 7e
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