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FRAGILE X SYNDROME

Most frequent form of inherited intellectual disability

1 in 4000 in 6000 in males

Prevalence in females is half of that in males

X-linked disorder

FMRP

Clinical features vary

Physical, cognitive and behavioural

Associated Conditions

Autism25% + 20% PDD NOS

Epilepsy10-20% M & 5% F

Clinical Features

Males

Full Mutation Significant impairment

Physical

Craniofacial

Mitral valve prolapse (50%)

Hypotonia, joint hyperlaxity

Testicular enlargement (>8yrs)

Cognitive

Global developmental delay

Intellectual disability

Learning disabilities

Behavioural

ADHD/ Anxiety/ ASD

Females

Full Mutation Variable


Impairment

Milder phenotype than male


counterpartslyonisation

50% have normal intellect

Some characteristic physical


features

Premature ovarian failure (20%


with premutation)

Long, narrow face

Prominent forehead & chin

Large ears

Sunken eyes

Strabismus

Diagnosis

Molecular genetic testing (FMR1 gene)

It is important to make the diagnosis asap so that appropriate


interventions can be initiated

American Academy of Paediatrics Committee on Genetics


recommends testing for FXS in children with any of the following:

Developmental delay

Borderline intellectual abilities

Mental retardation

Diagnosis of autism without a specific aetiology

Management

Educational Interventions

Speech and language therapy

Occupational therapy

Phamacotherapy

Stimulants

SSRIs

Antipsychotics

Anticonvulsant

Normal life expectancy

Genetic Counselling

Rett Syndrome

Neurodevelopmental disorder
that occurs almost exclusively in
females

MECP2 gene

>99% are sporadic mutations

Klinefelters syndrome/
mosaicism

Clinical Features

Developmentally normal for 1st 6 months!

Deceleration of head growth

12-18 months regression appears:

Fine motor, communicative and intellectual decline

Stereotypies

Inconsolable screaming

Rapid/ insidious

Period of partial recovery/ stabilization

Slow Deterioration

Decline in gross motor function (ataxic gait)

Growth failure (severe in 33%)

Scoliosis (70% by 16)

Epilepsy (80% by 15)

Respiratory dysfunction (70%)

ANS dysfunction (cardiac electrical instability)

Diagnosis

TYPICAL RETT SYNDROME

Regression followed by stabilization

All of:

Loss of purposeful hand movements

Loss of speech

Impaired gait

Stereotypies

None of:

Organic brain injury

Abnormal psychomotor development in 1st 6/12

Variants

Atypical

Preserved speech

less severe variant

Early seizure

2/4 main criteria + 5/11 supportive

epilepsy before 5 months

Congenital

onset in 1st 6 months

Management

MDT approach

Pharmacotherapy for associated conditions e.g. antiepileptic

Nutrition

ECG