Clinical scenario:
A 6-year-old girl is referred for short stature. Height is -2.5 SD, weight is proportionate, and she has a webbed neck and widely spaced nipples. Karyotype shows 45,X/46,XX mosaicism. Which of the following best explains why this patient may have a milder phenotype than classic Turner syndrome?
A. Presence of a normal cell line reduces the severity of haploinsufficiency of SHOX gene
B. Mosaicism increases the risk of gonadoblastoma, which is protective against growth failure
C. The 46,XX cell line is confined to the gonads only
D. SHOX gene is only active in the 45,X cell line
E. Mosaic Turner syndrome patients always have normal ovarian function
Correct answer & Explanation:
Answer: A — Milder phenotypes in mosaic Turner syndrome result from the presence of a normal cell line that partially compensates for SHOX haploinsufficiency and other X-linked gene dosage effects; the degree of mosaicism (and tissue distribution) determines phenotypic severity.
