Is Fragile X syndrome inherited, and what is the chance my other children could

[Anonymous]

Is Fragile X syndrome inherited, and what is the chance my other children could be affected?

[Genetic Counselor]

Yes – Fragile X syndrome follows an X-linked pattern, but with an important twist: the CGG repeat can grow larger as it passes from parent to child, so a parent’s own test result does not always predict a child’s outcome directly.

A man who carries a premutation (55–200 repeats) passes it to all of his daughters, because they inherit his X chromosome, and to none of his sons, because sons inherit his Y chromosome instead. His daughters become premutation carriers themselves but are not at risk of having a child with the full mutation directly from him – the repeat generally stays stable when passed from father to daughter.
A woman who carries a premutation faces a different situation: her repeat can expand when passed to her children, and the risk of expansion to a full mutation rises with the size of her own repeat. A woman with a full mutation has a 50 percent chance, with each pregnancy, of passing on the affected X chromosome to a child of either sex; whether that child is significantly affected depends partly on which sex they are, since a second X chromosome offers girls some protection.

Because the intermediate and premutation ranges can be present in a family for generations without anyone showing symptoms, a diagnosis in one child often prompts genetic counseling and testing for parents, siblings, and sometimes grandparents, aunts, uncles, and cousins on the maternal side. A genetic counselor can map the specific family pattern using the CGG repeat sizes found and, where relevant, AGG sequences that sit within the repeat and affect how likely it is to expand further. Prenatal testing is available for future pregnancies once a familial mutation is identified.

[Author]

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