A 14-year-old girl with Turner syndrome (45,X) is evaluated for short stature and primary amenorrhea. On examination, the structure marked **A** (webbed neck) is noted along with low posterior hairline, shield chest, and cubitus valgus. Which of the following best explains the pathophysiology underlying the webbed neck and other skeletal dysmorphology seen in this patient?
A. Mutation of the DAX1 gene causing adrenal hypoplasia congenita
B. Haploinsufficiency of the SHOX gene on the pseudoautosomal region of the X chromosome
C. Deletion of the SRY gene on the Y chromosome resulting in gonadal dysgenesis
D. Complete loss of the XIST gene leading to failure of X-inactivation
Explanation
Why haploinsufficiency of the SHOX gene is correct
The webbed neck (pterygium colli), short stature, cubitus valgus, low posterior hairline, and other skeletal dysmorphology in Turner syndrome are directly caused by haploinsufficiency of the SHOX gene located on the pseudoautosomal region of the X chromosome. In 45,X individuals, there is only one copy of the SHOX gene instead of the normal two, leading to insufficient gene dosage and the characteristic skeletal and connective tissue abnormalities. This is the established molecular basis for the skeletal phenotype in Turner syndrome (Nelson Textbook of Pediatrics 21e).
Why each distractor is wrong
Complete loss of the XIST gene: XIST is responsible for X-inactivation in normal XX females. While Turner syndrome involves abnormal X chromosome dosage, the skeletal dysmorphology is not caused by XIST dysfunction; rather, it results from SHOX haploinsufficiency. XIST loss would not explain the specific pattern of webbed neck and skeletal features.
Mutation of the DAX1 gene: DAX1 mutations cause adrenal hypoplasia congenita and X-linked adrenal insufficiency, not the skeletal dysmorphology of Turner syndrome. While Turner syndrome does involve gonadal dysgenesis, this is due to streak gonads from accelerated oocyte loss, not DAX1 mutations.
Deletion of the SRY gene: SRY is located on the Y chromosome and is responsible for testis-determining factor. Turner syndrome (45,X) involves complete or partial absence of the X chromosome, not Y chromosome abnormalities. SRY deletion would be relevant in XY gonadal dysgenesis, not Turner syndrome.
High-YieldNEET PG
SHOX haploinsufficiency on the pseudoautosomal region explains the short stature and skeletal dysmorphology (webbed neck, cubitus valgus, low hairline) in Turner syndrome; streak gonads and oocyte loss explain the gonadal failure and primary amenorrhea.
Nelson Textbook of Pediatrics 21e — Turner Syndrome section
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