Fragile X Syndrome
What is Fragile X Syndrome?
Fragile X Syndrome (FXS) is a genetic disorder caused by a mutation in the FMR1 (scientists call this “Fragile X Mental Retardation 1”) gene (please note: we wouldn’t use this word if it weren’t the scientific name). The gene is located on the X chromosome and found in nearly every tissue of the body.
This gene tells the body how to make a specific protein, the FMR protein (aka FMRP). This protein is needed for normal brain development. With Fragile X syndrome, the gene either does not make this protein or does not make enough of it.
The condition causes a variety of developmental issues including learning disabilities, behavior issues, and cognitive impairment. [1]
This condition occurs in 1 in 4,000 males and 1 in 8,000 females. It is the most common cause of inherited intellectual disability. Intellectual impairment is typically milder in females than males. [1]
Fragile X syndrome is diagnosed with genetic testing via a blood test.
Signs & Symptoms
Developmental delays in childhood milestones. Most parents notice these before their child’s first birthday.
Learning disabilities
Social and behavioral issues
Certain physical features
Prominent forehead
Large ears
Long face
Prominent jaw
Hypotonia (low muscle tone)
Next Steps
Diet
People with both Fragile X Syndrome and ASD were about 3 times more likely to experience seizures than people with FXS alone. [7]
The ketogenic diet may be of consideration for those experiencing seizures, as it alone selectively reduces seizures and weight gain in male fragile x mice. [3]
In one study, the Specific Carbohydrate Diet was investigated as potential diet therapy for Fragile X Syndrome. The results indicated that the diet was well tolerated. Improvements in nutrient status, GI symptoms, and behavioral domains were reported. The use of the SCD protocol in children with ASD/FXS and GI symptoms warrants further investigation. [5]
Since there is no known cure for either Fragile X Syndrome or Autism, nutritional strategies should focus on addressing root causes of symptoms that co-occur with FXS and/or ASD. For example, irritability or self-injury may be caused by pain due to inflammation from an underlying or unaddressed food sensitivity. Biomedical testing can help provide clarity on potential underlying causes of visible symptoms. Nutritional strategies may not cure or reverse Fragile X Syndrome or autism but they may help reduce or eliminate symptoms associated with the condition and improve the person’s quality of life.
Supplements
Lithium is both a psychiatric medication and trace element/dietary supplement that has been explored in animal models.
Anxiety and hyperactivity were reversed in mouse models with lithium treatment. [9]
Omega 3 supplementation has shown promise in animal studies.
Juvenile and adult Fragile X rats showed deficits in the social and cognitive domains, which were counteracted by perinatal omega-3 PUFAs supplementation. [4] (See also: Fish Oil)
Omega-3 PUFA supplementation rescued most of the behavioral abnormalities displayed by Fragile X mice, including alterations in emotionality, social interaction, and non-spatial memory, along with most neuroinflammatory imbalances. [6]
Further research is needed on prenatal exposure to high omega-3s and a high-fat diet as a potential treatment for communication deficits Fragile X syndrome. [8]
DISCLAIMER: Before starting any supplement or medication, always consult with your healthcare provider to ensure it is a good fit for your child. Dosage can vary based on age, weight, gender, and current diet.
Lifestyle
Obesity is more likely in males with FXS than typically developing males. [7]
Steps should be taken to ensure a balanced and nutritious diet, and adequate physical activity.
Providing opportunities for physical activity is also important because physical exercise not only counteracts obesity but also brain injury in ASD patients. Exercise promotes brain vascularization and stimulates neuronal and glial genesis. Exercise also enhances memory and cognitive functions. [10]
Approximately 4 in 10 people with both FXS and ASD had sleep problems that required treatment, compared to 3 in 10 people with FXS alone. [7] There are many simple lifestyle modifications that can help children fall asleep and stay asleep.
Toilet training can be a challenge but there are many resources available to help parents and caregivers achieve this milestone. [12]
Feeding can be another challenge both for children with Autism and FXS. Both feeding and behavioral therapists can assist with this daily activity. [13] (See: Picky Eating note)
Education and Therapies
Early intervention services for children 0-3 years old and special education for older children, including an individualized education plan (IEP), appropriate therapies (occupational, physical, speech/language, feeding, behavioral) and family support, give children the greatest chance of developing a full range of skills. [9]
Other helpful lifestyle considerations include [11]
Developing a consistent daily routine
Determine the person’s individual learning style
Using visual signs to communicate instructions or ideas
Preparing the child for change in advance by explaining and giving forewarning before changes occur
Providing quiet places where a child can calm down and gather themselves when overwhelmed
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[1] CDC. Fragile X Syndrome (FXS). Cdc.gov. Published November 13, 2020. Accessed January 8, 2021. https://www.cdc.gov/ncbddd/fxs/index.html
[2] NFXF. The similarities and differences between FXS and autism. Fragilex.org. Published December 18, 2014. Accessed January 8, 2021. https://fragilex.org/support-and-resources/fragile-x-syndrome-and-autism-spectrum-disorder-similarities-and-differences/
[3] Westmark PR, Gutierrez A, Gholston AK, Wilmer TM, Westmark CJ. Preclinical testing of the ketogenic diet in fragile X mice. Neurochem Int. 2020;134:104687.
[4] Schiavi S, Carbone E, Melancia F, et al. Perinatal supplementation with omega-3 fatty acids corrects the aberrant social and cognitive traits observed in a genetic model of autism based on FMR1 deletion in rats. Nutr Neurosci. 10.1080/1028415X.2020.1819107
[5] Barnhill K, Devlin M, Moreno HT, et al. Brief Report: Implementation of a Specific Carbohydrate Diet for a Child with Autism Spectrum Disorder and Fragile X Syndrome. J Autism Dev Disord. 2020;50(5):1800-8.
[6] Pietropaolo S, Goubran MG, Joffre C, et al. Dietary supplementation of omega-3 fatty acids rescues fragile X phenotypes in Fmr1-Ko mice. Psychoneuroendocrinology. 2014;49:119-29.
[7] CDC. Data and Statistics on Fragile X Syndrome. Cdc.gov. Published July 16, 2020. Accessed January 8, 2021. https://www.cdc.gov/ncbddd/fxs/data.html
[8] Nolan SO, Hodges SL, Okoh JT, Binder MS, Lugo JN. Prenatal High-Fat Diet Rescues Communication Deficits in Fmr1 Mutant Mice in a Sex-Specific Manner. Dev Neurosci. 10.1159/000509797
[9] Liu Z, Smith CB. Lithium: a promising treatment for fragile X syndrome. ACS Chem Neurosci. 2014;5(6):477-83.
[10] Lee M, Won J, Lee S, Hong Y, Kim JH, Hong Y. Benefits of Physical Exercise for Individuals with Fragile X Syndrome in Humans. J Lifestyle Med. 2015;5(2):35-8.
[11] Educational Treatments. Nih.gov. Accessed January 8, 2021. https://www.nichd.nih.gov/health/topics/fragilex/conditioninfo/EducationalTreatments
[12] Fragilex.org. Accessed January 8, 2021. https://fragilex.org/wp-content/uploads/Toileting-Issues-in-Fragile-X-syndrome-Dec-2019.pdf
[13] NFXF. Feeding and Fragile X. Fragilex.org. Published September 14, 2016. Accessed January 8, 2021. https://fragilex.org/treatment-and-intervention/feeding-and-fragile-x/
Authors
Elisa Rocks, RDN
Edited & Reviewed by Brittyn Coleman, MS, RDN/LD, CLT
