SYNGAP1-Related Intellectual Disability

 

James Clement, PhD studied as a post-doc under Super Syngapian Scientist, Gavin Rumbaugh, PhD from 2010-13.
Dr. Clement is the author of 'SynGAP1: Mind the Gap.' and he offered SGN to create with the help of his student a lay man summary of one of the latest paper published by Jimmy Holder, PhD:

SYNGAP1 Encephalopathy

The brain is a complex organ that functions as the coordinating system of the body. Any influence posed to the brain during its development due to environmental or genetic influence can potentially lead to neurodevelopmental disorders, including Intellectual Disability and Autism Spectrum Disorders and Epileptic Encephalopathy. SYNGAP1 related intellectual disability (SYNGAP1-ID) is one of the most important neurodevelopmental disorders characterized by significant impairments in the ability to learn, think, and adapt to the surrounding.

SYNGAP1 gene is a critical player in early brain development, which produces a protein essential for learning and memory. Mutation(s) in a single copy of the gene lead(s) to a reduction in the levels of SYNGAP1 protein by at least half, eventually leading to the symptomologies of intellectual disability, involving cognitive and behavioural deficits. The condition can also be characterised by aversion to social situations and speech impediments.

A recent study by Vlaskamp et al that was published in the journal ‘Neurology’ involved 57 patients with SYNGAP1 mutations. The investigating group took intricate notice into each patient’s phenotype, medical records from neuroimaging, MRI and EEG (electroencephalogram) reports, and seizure videos. In this study, they have highlighted the clinical characteristics, Diagnosis/testing, management and genetic counselling of patients with SYNGAP1 mutation.

Highlights of their study:

  • 53% of the patients studied were males and 8 years of median age.

  • Thirty-nine patients were found to have novel, de novo mutations in the SYNGAP1 gene.

  • Seizures appeared to be a very common feature, seen in 56 of the 57 subjects.

  • 93% of the patients showed absence seizures, as characterized by a sudden lapse in attention.

  • For the first time, they observed a combination of two epileptic syndromes in 35% of total patients. The patient faces a sudden eyelid myoclonic (eyelid fluttering) with drop attack and followed by myoclonic-atonic seizures.

  • 68% of the patients had eating problems, whereas 25% of them had seizures which were triggered by eating.

  • Proportion of patients as high as 72 % showed high threshold of tolerance for pain, sometimes leading to the delay in diagnosing of injuries and inflammation, suggesting a role of SYNGAP1 in sensory processing.

  • 73% had behavioural problems, and 51% faced a problem with their body balance and had gait abnormalities. 67% also had low muscle tone.

  • Among 57 patients, 55 had an intellectual disability (ID).

  • 62% had sleeping problems and 54% had an autism diagnosis.

This paper brings about a very important lacunae between science and society, an existing lack of awareness in ‘Syngap families’ about the ongoing research. Right in between the two parties of scientists and clinicians are patients and their families, who, right from the very beginning, need not only an understanding of the science behind the pathological symptoms, but also of the potential intervention therapies available.

 

However, beside all these are other families, whose children might be exhibiting mild symptoms, but are unaware of those. As such, awareness related to this must reach through to every households, making use of the available medical technologies, be it delayed onset of developmental milestone or classical epileptic symptoms, for better use of behavioural therapies

Reference:

SYNGAP1-Related Intellectual Disability Synonym: SYNGAP1-Related Developmental and Epileptic Encephalopathy J Lloyd Holder, Jr, MD, PhD, Fadi F Hamdan, PhD, and Jacques L Michaud, MD. GeneReviews® [Internet]. Adam MP, Ardinger HH, Pagon RA, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2019. (https://www.ncbi.nlm.nih.gov/books/NBK537721/)

 

 

Fulll paper link : https://www.ncbi.nlm.nih.gov/books/NBK537721/?fbclid=IwAR2MhC4dVFw7FtWHbUmyToN_JNXGWC3MzL37pQGHruElA1TyKRXcV1mHqio