Phelan McDermid Syndrome
What is Phelan McDermid Syndrome?
Phelan McDermid Syndrome (PMS) is a rare genetic condition caused by a mutation or deletion of chromosome 22. [1] This may or may not impact the SHANK3 gene and PMS may be referred to as PMS-SHANK3 related or PMS-SHANK3 unrelated. [5]
The condition causes developmental and speech delays, behavioral problems, and low tone (hypotonia). 75% of those with PMS are also diagnosed with autism spectrum disorder. It is estimated that 1% of all people with autism have PMS. [2]
In terms of the general population, Phelan McDermid syndrome is very rare and occurs in about 2-10 in 1 million births. However, it is likely underdiagnosed. It occurs equally in males and females. [3]
There are no characteristic structural abnormalities that allow diagnosis by an ultrasound exam before birth although some tests prenatal tests like amniocentesis and/or chorionic villus sampling (CVS) may be able to detect PMS. [3]
After birth, the diagnosis of PMS is based on genetic testing for the identification of a deletion or disruption of the chromosome region 22q13. [3]
75% of those with PMS are also diagnosed with autism spectrum disorder.
Signs & Symptoms
Symptoms of Phelan McDermid syndrome are often noticeable very early on, within the first 6 months of life and even more so in early childhood. [2]
Symptoms include [2]:
Low muscle tone (hypotonia)
Developmental delay (not achieving typical milestones like sitting up, crawling, rolling, walking or talking)
Repetitive behaviors
Delayed speech and language
Seizures (in about 40% of people)
High pain tolerance
Reduced sweating which makes it difficult to regulate temperature and puts them at risk for overheating
Contributing Factors
Most cases occur randomly in-utero due to genetic mutations. [3]
Most cases of PMS are due to a spontaneous break in the long arm of chromosome 22 that occurs for unknown reasons. The segment of chromosome 22 beyond the break is lost (deleted). In such cases, called simple deletions, the disorder is not inherited from the parents. [3]
Ring 22 is another structural chromosome change that can result in PMS. Chromosome 22 breaks at both ends (i.e., the ends of the long arm [22q] and the short arm [22p]) and the distal segments are lost (deleted). The “new” chromosomal ends then join, forming a circular structure, or ring. About 14-33% of individuals with PMS carry a ring 22, although this is likely to be an underestimate. The formation of the ring is usually accompanied by a similar loss of genetic material as seen in cases of 22q13 deletion, and the symptoms observed to date appear to be consistent between the two conditions. [3]
Next Steps
Diet
Because so many people with PMS are also diagnosed with autism spectrum disorder, many of the same nutritional considerations apply. An experienced nutrition practitioner can help determine if the child with PMS has:
Nutritional deficiencies
Physical feeding challenges
Sensory challenges that impact feeding
Food sensitivities that may be causing inflammation
Gastrointestinal problems like constipation, digestive insufficiency or intestinal permeability
Supplements
Because so many people with PMS are also diagnosed with autism spectrum disorder, many of the same supplement considerations apply.
Those with autism, and especially selective eaters, are at risk for many nutritional deficiencies. A skilled practitioner can evaluate the child’s diet, using micronutrient testing and/or diet analysis to determine what vitamins, minerals or macronutrients need to be prioritized in the diet or supplemented in cases where the diet isn’t meeting nutritional needs.
There is some research to suggest that supplementation with zinc, b vitamins, coq10 ubiquinol and vitamin E may be beneficial for children with neurodevelopmental disorders. [7,8]
Lifestyle
Many lifestyle considerations center around treatments for the symptoms of PMS, which can vary from person to person. Forming a team of experienced practitioners can make all the difference. When seeking out your team, look for a:
Developmental pediatrician (pediatricians can often refer out to other medical specialists if needed)
Registered Dietitian with experience working with children developmental delays or autism
Occupational therapist
Behavioral therapist
Speech therapist
Physical therapist
Feeding therapist
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.
Phelan McDermid Syndrome & Autism in the Research
Gut Issues
Parent-reported history of symptoms were common: constipation (65%), reflux (59%), choking/gagging (41%), and more than half received gastrointestinal specialty care. Incontinence is common in PMS and associated with intellectual functioning and gene deletion size. Management strategies may differ based on the presence of non-retentive fecal incontinence, functional constipation, and degree of intellectual disability for children with PMS. [4]
In a mouse model, SHANK3 proteins are not only expressed in the central nervous system but also in the gastrointestinal (GI) epithelium. Further, we detected a significantly altered microbiota composition measured in feces of Shank3 KnockOut mice that may contribute to inflammatory responses affecting brain development. In line with this, we found higher E. coli lipopolysaccharide levels in liver samples of Shank3 KO mice, and detected an increase in Interleukin-6 and activated astrocytes in Shank3 KO mice. We conclude that apart from its well-known role in the CNS, SHANK3 plays a specific role in the GI tract that may contribute to the ASD phenotype by extracerebral mechanisms. [6]
Supplements
Zinc deficiency (assessed by either dietary intake, blood, hair, or tooth matrix) was shown to be highly prevalent in ASD and PMS patients as well as in preclinical models of ASD and PMS. Zinc supplements improved the behavioral deficits in animal models of ASD and PMS. [7]
This retrospective chart review suggests that metabolic support therapy with Q10 ubiquinol, vitamin E and complex-B vitamins is well tolerated and produces some improvement in the majority of patients with neurodevelopmental disorders, especially in the presence of intellectual disability. [8]
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[1] Home - Phelan-McDermid Syndrome Foundation - An international alliance of science and support. Phelan-McDermid Syndrome Foundation. Published December 26, 2018. Accessed December 10, 2022. https://pmsf.org/
[2] What is Phelan-McDermid syndrome? Phelan-McDermid Syndrome Foundation. Published December 28, 2020. Accessed December 10, 2022. https://pmsf.org/about-pms/
[3] Phelan-McDermid syndrome - NORD (national organization for Rare disorders). NORD (National Organization for Rare Disorders). Published February 11, 2015. Accessed December 10, 2022. https://rarediseases.org/rare-diseases/phelan-mcdermid-syndrome/
[4] Witmer C, Mattingly A, DʼSouza P, Thurm A, Hadigan C. Incontinence in Phelan-McDermid Syndrome. J Pediatr Gastroenterol Nutr. 2019;69(2):e39-e42.
[5] Phelan K, Boccuto L, Powell CM, et al. Phelan-McDermid syndrome: a classification system after 30 years of experience. Orphanet J Rare Dis. 2022;17(1):27.
[6] Sauer AK, Bockmann J, Steinestel K, Boeckers TM, Grabrucker AM. Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model. Int J Mol Sci. 2019;20(9):2134.
[7] Alsufiani HM, Alkhanbashi AS, Laswad NAB, et al. Zinc deficiency and supplementation in autism spectrum disorder and Phelan-McDermid syndrome. J Neurosci Res. 2022;100(4):970-8.
[8] Cucinotta F, Ricciardello A, Turriziani L, et al. Efficacy and Safety of Q10 Ubiquinol With Vitamins B and E in Neurodevelopmental Disorders: A Retrospective Chart Review. Front Psychiatry. 2022;13:829516.
