34 HOW TO TREAT : FRAGILE X SYNDROME
34 HOW TO TREAT : FRAGILE X SYNDROME
6 DECEMBER2024 ausdoc . com . au
Box 6 . Testing for FXS
• FXS testing for :
— People with intellectual disability , developmental delay or learning disability , together with features of FXS such as anxiety , ADHD or autism-like behaviours .
• Fragile X premutation carrier testing for : — People with a family history of FXS , intellectual disability or autism spectrum disorders . — Men or women over 50 years of age with shaking ( intention tremor ), unsteadiness ( ataxia ), dementia or other Parkinson ’ s-like features . — All women considering pregnancy or in the early stages of pregnancy
( during the first 12 weeks ). — Any woman with primary ovarian insufficiency or experiencing early menopause .
Protic DD et al . Int J Mol Sci 2022 / CC BY 4.0 / bit . ly / 3YzrAHh
Source : Fragile X Association of Australia 13
pharmacological modalities . Medication includes metformin 50mg a day , and clonidine 25μg with breakfast and lunch , and 50μg before bed to assist with impulsive aggressive behaviour during the day and sleep onset at night .
Methylphenidate 5mg immediate release ( 1 / 2 of 10mg immediate release tablet ) is added a few weeks later to assist further with hyperactivity and concentration , in the morning with breakfast , and four hours later with lunch .
Jack receives speech therapy , occupational therapy and behavioural therapy to aid with his anxiety and tantrums . This is all funded via the NDIS pathway .
Genetic testing of his family reveals FXS premutations with CGG counts of 105 and 68 in his mother and maternal grandmother , respectively .
1 . Which THREE statements regarding FXS are correct ? a It is the leading inherited cause of intellectual developmental disorder . b An association has not been demonstrated between FXS and ASD . c FXS may cause cognitive , behavioural and physical abnormalities . d Males with FXS typically present in the first two years of life .
2 . Which TWO statements regarding FXS are correct ? a Males with a full mutation frequently present only with learning disabilities , socioemotional difficulties and mental health issues . b The presentation in females may be milder . c Females are frequently treated for the specific developmental concern but not tested for FXS and are therefore misdiagnosed . d The prevalence of full mutation FXS is more common than those with the premutation carriers .
3 . Which THREE statements regarding the genetics of FXS are correct ?
Case study two
Elsa , a six-year-old girl , presents to the child development unit together with her parents . The parents are concerned about Elsa ’ s speech delay , social anxiety and a preference for routine and sameness .
Elsa had previously been referred by her GP to a speech therapist , and her expressive language is making slow progress , although she often refuses to speak in public and hides behind her mother . The GP had also requested a hearing assessment , which was within normal limits . No other investigations were requested . The preschool requested a more formal developmental assessment , as there were concerns regarding her pre-academic skills , attention and concentration . The staff had noted that Elsa struggled with following instructions , refused to eat at preschool , tended to play repeatedly with the
How to Treat Quiz .
a Premutation carriers are always asymptomatic . b Fathers with a premutation will pass on their premutation to all their daughters and not their sons . c There is a 50 % chance of a mother passing on her affected X chromosome equally to her sons and daughters . d The FMRP levels are a key factor in the severity of the presentation .
4 . Which ONE is not a physical feature of FXS ? a Hypotonia . b Hypogonadism . c Large ears . d Hyperflexible joints .
5 . Which THREE are the most commonly encountered behavioural issues in FXS ? a Anxiety . b Avoidance . c Arousal . d Lack of stranger danger .
Figure 10 . A schematic presentation of non-pharmacological interventions for fragile X syndrome .
same toys , and would hand flap and rock when she was distressed .
The pregnancy with Elsa was uncomplicated . She was an irritable neonate and experienced reflux and sleep difficulties . Her parents could never leave her with a babysitter because she became very distressed , and attempts to take her to preschool failed because of extreme separation anxiety . Elsa is the eldest of three children to a non-consanguineous couple , both with successful careers ; the
GO ONLINE TO COMPLETE THE QUIZ ausdoc . com . au / how-to-treat
6 . Which ONE is not a differential diagnosis of FXS ? a ASD without FXS . b ADHD without FXS . c Prader-Willi syndrome . d Cerebral palsy .
7 . Which TWO statements regarding FXS are correct ? a About 50 % of males with
FXTAS develop dementia . b FXTAS occurs in up to 50 % of men and women over the age of 60 with the FXS premutation . c Anxiety often presents in childhood in premutation carriers . d Females with an FXS premutation can develop primary ovarian insufficiency in childhood .
EARN CPD OR PDP POINTS
• Read this article and take the quiz via ausdoc . com . au / how-to-treat
• Each article has been allocated one hour by the RACGP and ACRRM .
• RACGP points are uploaded every six weeks and ACRRM points quarterly .
FRAGILE X SYNDROME
father is a lawyer and the mother a social worker . The middle child is a three-year-old boy who has global developmental delay and is awaiting assessment at the child development unit . The youngest child , a ninemonth-old boy , has been diagnosed with very low tone , with feeding difficulties and significantly delayed motor milestones .
On formal assessment , Elsa is diagnosed with a mild intellectual disability with more severely impaired
8 . Which THREE statements regarding the management of FXS are correct ? a Genetic counselling is the cornerstone of prevention . b Always use medication in conjunction with nonpharmacological strategies . c The alpha-2 adrenergic receptor agonists are the first-line pharmacological treatment for ADHD . d SSRIs are usually the firstline treatment for managing anxiety .
9 . Which TWO statements regarding the management of FXS are correct ? a It is vital to understand the drivers for behavioural issues . b Mitral valve incompetence , middle ear infection , hernias and musculoskeletal conditions are common and require anticipatory guidance and active management . c Risperidone is the drug of choice for sleep disorders in FXS . d Methylphenidate is the drug of choice in FXS with ASD .
10 . In which THREE groups is fragile X testing recommended ? a Any woman with primary ovarian insufficiency . b All women considering pregnancy or in the first trimester of pregnancy . c Those with a family history of fragile X syndrome . d All children with recurrent otitis media . language skills . Her severe anxiety meets the DSM-5-TR for a diagnosis of generalised anxiety disorder . While some features of autism are noted , Elsa does not meet the full criteria for a formal diagnosis of autism .
Elsa is treated with a combination of medication ( metformin 100mg a day , fluoxetine initially 10mg a day and then increased to 20mg a day two months later ) for her anxiety , and multidisciplinary intervention that includes speech therapy and sessions with a clinical psychologist . As Elsa is due to start school the following year , consideration is given to enrolling her in a support class placement in a mainstream school .
On investigation for FXS , Elsa is found to have 800 CGG repeats . Both her brothers are subsequently identified to have a full mutation for FXS and are diagnosed with moderate developmental delay and autism spectrum disorder . Cascade testing of the extended family identifies three female premutation carriers of childbearing age who undergo genetic consultation and discussions around family planning options .
CONCLUSION
FXS is the leading inherited cause of intellectual developmental disorder and the leading single gene cause of ASD .
GPs are in a unique position to identify developmental concerns early , investigate appropriately and refer for multidisciplinary individualised intervention . While there is no cure for FXS , much can be done to improve the lives and prognosis of those affected . Furthermore , a diagnosis of FXS has broad ramifications and benefits . It may impact family planning and the understanding and management of health conditions of individuals in the extended family that may otherwise have been misdiagnosed .
RESOURCE
Fragile X Association of Australia : Web — www . fragilex . org . au Helpline — 1300 394 636
References Available on request from howtotreat @ adg . com . au