Related Experiment Videos
Three families with mild PMM2-CDG and normal cognitive development
Mari-Anne Vals1,2,3, Eva Morava4,5, Kai Teeäär6
1Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.
American Journal of Medical Genetics. Part A
|April 21, 2017
Summary
This study identifies mild variants of PMM2-congenital disorder of glycosylation (CDG) in six patients with normal cognitive development, delayed motor skills, and mild neurological findings. Specific PMM2-CDG genotypes may be associated with these milder clinical presentations.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Congenital disorders of glycosylation (CDG) result from impaired protein and lipid glycosylation.
- PMM2-CDG is the most prevalent CDG subtype, typically presenting with variable, often severe, neurological and multisystemic symptoms.
- Mild PMM2-CDG phenotypes are less commonly documented, particularly those with normal cognitive development.
Purpose of the Study:
- To describe the clinical and genetic characteristics of patients with a clinically mild form of PMM2-CDG.
- To investigate potential genotype-phenotype correlations in PMM2-CDG.
- To highlight the variability in PMM2-CDG presentation and diagnostic timing.
Main Methods:
- Clinical assessment of six patients from three families with suspected PMM2-CDG.
- Neurological examination and brain MRI.
- Cognitive assessment using the Wechsler Intelligence Scale for Children (WISC).
- Genetic analysis to identify PMM2 gene mutations.
Main Results:
- All six patients exhibited delayed gross motor skills and mild-to-moderate neurological findings.
- Cerebellar hypoplasia was observed in all siblings who underwent brain MRI.
- Five out of six children demonstrated normal cognitive development (WISC full scale IQ scores from borderline to average).
- Four patients were diagnosed with PMM2-CDG after age 8 due to mild symptoms and regular school participation.
- Identified genotypes include p.Val231Met/p.Arg239Trp and p.Ile120Thr/p.Gly228Cys, potentially linked to milder PMM2-CDG variants.
Conclusions:
- Mild PMM2-CDG variants can present with normal cognitive development and delayed motor skills.
- Cerebellar hypoplasia may be a consistent finding even in milder cases.
- Delayed diagnosis is possible in PMM2-CDG patients with subtle neurological symptoms.
- Specific PMM2 genotypes may predispose individuals to milder PMM2-CDG phenotypes.