Genotype-phenotype correlations exist (see table below) and this Inform on prognosis: information is useful in helping to counsel families on what to expect clinically.2 Types of FMR1 Repeat Expansion Mutations Number of CGG Clinical Status Mutation Methylation Status Trinucleotide Type of FMR1 Male Female Repeats At risk for ~55-200 Unmethylated At risk for FXTAS POI and Premutation FXTAS ~50% with Completely ID, ~50% >200 100% with MR Full methylated normal intellect Partial: Varies between unmethylated in the premutation and premutation cell line; Repeat size full in different Nearly 100% with ID; methylated in the cell lines may be higher full- cell line Highly functioning than Partial: mixture of variable: males with full methylated and ranges from >200 Methylation unmethylated cell normal lines intellect to Nearly all have ID but often have Unmethylated >200 Unmethylated full MR to intellect ID=intellectual disability The following Change treatment plan (e.g. medical or surgical decision-making or treatment). evaluations are recommended following initial diagnosis:2 developmental and educational assessments ●Complete and psychological evaluations ●Behavioral assessments in infants ●Feeding auscultation for mitral valve prolapse with consideration of ●Cardiac echocardiography if a murmur is detected monitoring ●Hypertension threshold for seizure concern given the increased risk ●Low evaluation for strabismus ●Ophthalmologic for recurrent otitis media ●Monitoring
Inform on prognosis: Genotype-phenotype correlations exist (see table below) and this information is useful in helping to counsel families on what to expect clinically.2 Types of FMR1 Repeat Expansion Mutations Mutation Type Number of CGG Trinucleotide Repeats Methylation Status of FMR1 Clinical Status Male Female Premutation ~55-200 Unmethylated At risk for FXTAS At risk for POI and FXTAS Full >200 Completely methylated 100% with MR ~50% with ID, ~50% normal intellect Repeat size Varies between premutation and full in different cell lines Partial: unmethylated in the premutation cell line; methylated in the full- cell line Nearly 100% with ID; may be higher functioning than males with full Highly variable: ranges from normal intellect to Methylation >200 Partial: mixture of methylated and unmethylated cell lines Unmethylated full >200 Unmethylated Nearly all have ID but often have MR to intellect ID=intellectual disability Change treatment plan (e.g. medical or surgical decision-making or treatment). The following evaluations are recommended following initial diagnosis:2 ●Complete developmental and educational assessments ●Behavioral and psychological evaluations ●Feeding assessments in infants ●Cardiac auscultation for mitral valve prolapse with consideration of echocardiography if a murmur is detected ●Hypertension monitoring ●Low threshold for seizure concern given the increased risk ●Ophthalmologic evaluation for strabismus ●Monitoring for recurrent otitis media
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