Fragile X syndrome — formative SAQs

SAQ 1 (10 marks)

A three-year-old boy is referred for global developmental delay and "autistic features". He walked at 20 months and has fewer than ten single words. His mother's brother has intellectual disability and lives in supported accommodation. A previous paediatrician sent a chromosomal microarray, which returned normal. The parents ask why you are ordering more tests. ^{[1] [5]}

a) Explain why a normal chromosomal microarray does not exclude fragile X syndrome, and name the specific two-part molecular test you will order. (3 marks) ^{[1] [5]}

b) Define the four FMR1 CGG-repeat allele classes, giving the repeat boundaries and methylation status of each. (3 marks) ^{[3] [5]}

c) Outline the comorbidity-driven management plan for this child, naming four domains beyond the genetic result that require active surveillance and support. (2 marks) ^[1]

d) Describe the cascade-testing obligation to the wider family, including the premutation-associated conditions you would screen for in his mother. (2 marks) ^{[1] [9]}