Ataxia-Telangiectasia (AR) MCQ — NEET PG Practice Question | NEETPGAI
Ataxia-Telangiectasia (AR)
medium
stethoscope Medicine
A 7-year-old girl is referred for progressive gait instability since age 18 months. On examination, she has cerebellar ataxia with truncal titubation, oculomotor apraxia with head thrusts to initiate saccades, and telangiectasias over the bulbar conjunctivae and nasal bridge. Laboratory studies show low serum IgA, low IgG2, and markedly elevated alpha-fetoprotein. Her parents are first cousins with no family history of similar disease in previous generations. Her older brother was similarly affected and died of T-cell leukemia at age 12. The pedigree pattern shown in the diagram at **B** is most consistent with which inheritance pattern?
A. X-linked recessive with male predominance
B. Autosomal recessive with consanguinity
C. Autosomal dominant with incomplete penetrance
D. Y-linked inheritance with paternal transmission only
Explanation
Why "Autosomal recessive with consanguinity" is right
The clinical presentation—progressive cerebellar ataxia, oculomotor apraxia, telangiectasias, immunodeficiency (low IgA, IgG2), elevated alpha-fetoprotein, and recurrent infections—is pathognomonic for Ataxia-Telangiectasia (A-T). The pedigree pattern at B shows the hallmark features of autosomal recessive inheritance: (1) affected siblings (the proband and her older brother) born to unaffected parents, (2) consanguinity (first-cousin parents), (3) horizontal transmission (single generation affected), and (4) equal sex distribution. This pattern is diagnostic of AR inheritance. A-T results from biallelic loss-of-function mutations in the ATM gene on chromosome 11q22-23, encoding the ATM protein—a master regulator of DNA double-strand break response. Consanguinity increases the probability of rare recessive alleles meeting in offspring (Gatti & Perlman, GeneReviews — Ataxia-Telangiectasia).
Why each distractor is wrong
Autosomal dominant with incomplete penetrance: AD inheritance shows vertical transmission across generations (affected parent to affected child). Here, both parents are unaffected, ruling out AD. Incomplete penetrance would not explain why both unaffected parents have two affected children.
X-linked recessive with male predominance: X-linked recessive shows affected males with carrier mothers; affected females are rare. This pedigree has an affected female (the proband) with an affected brother and unaffected parents—inconsistent with X-linked inheritance, which would require the mother to be at least a carrier (and typically symptomatic if homozygous).
Y-linked inheritance with paternal transmission only: Y-linked inheritance shows father-to-son transmission only. Here, the proband is female and affected, which is impossible with Y-linked inheritance. Additionally, the father is unaffected.
High-YieldNEET PG
Ataxia-Telangiectasia is autosomal recessive; consanguinity + affected siblings with unaffected parents = AR. Elevated AFP is the pathognomonic biochemical marker (>95% of A-T patients). Avoid ionizing radiation in these patients due to profound radiosensitivity from ATM deficiency.
