Familial Turner Syndrome With Distinct Karyotypes in Two Cousins: Phenotypic Convergence and Genotypic Heterogeneity

Area of Science:

• Genetics
• Endocrinology
• Reproductive Medicine

Background:

• Familial Turner syndrome (TS) is rare, usually involving identical X-chromosome aberrations.
• Distinct karyotypes within the same generation are exceptionally rare, posing challenges for genetic counseling.

Purpose of the Study:

• To report a rare case of familial TS with phenotypic uniformity despite genotypic heterogeneity.
• To investigate the underlying genetic mechanisms and implications for counseling.

Main Methods:

• Case report of two cousins with primary amenorrhea and hypogonadism.
• Karyotyping, pelvic ultrasonography, cardiac and renal screening.
• Whole-exome sequencing, copy number variation analysis, and literature review.

Main Results:

• Two cousins presented with similar TS phenotypes but distinct karyotypes: 46,X,i(X)(q10) and 45,X.
• No pathogenic variants in known TS loci were found; mosaicism was not excluded.
• Literature review confirmed the rarity of this genotypic heterogeneity.

Conclusions:

• Functional haploinsufficiency of the X-chromosome short arm (Xp) may explain the uniform TS phenotype despite varying cytogenetic errors.
• Familial TS can arise from different mechanisms, necessitating broad prenatal screening and careful counseling on heritability.