Clinical studies on submicroscopic subtelomeric rearrangements: a checklist
B B de Vries1, S M White, S J Knight
1Clinical and Molecular Genetics Unit, Institute of Child Health and Great Ormond Street Hospital, London, UK.
Journal of Medical Genetics
|March 10, 2001
Summary
Submicroscopic subtelomeric chromosome defects are linked to prenatal growth issues and family history of intellectual disability. A new checklist aids in identifying these genetic conditions in children with developmental delays.
Area of Science:
- Genetics
- Developmental Biology
- Clinical Diagnostics
Background:
- Submicroscopic subtelomeric chromosome defects occur in a significant percentage of children with mental retardation.
- Clinical preselection is crucial due to the complexity and cost of subtelomere deletion screening.
Purpose of the Study:
- To identify clinical indicators for subtelomeric defects in children with mental retardation.
- To develop a checklist for improved diagnostic accuracy of subtelomeric abnormalities.
Main Methods:
- Studied 29 patients with known subtelomeric defects and assessed clinical variables.
- Compared cases with 110 children with mental retardation and normal karyotypes (controls).
- Assessed birth history, facial dysmorphism, congenital malformations, and family history.
Main Results:
- Prenatal growth retardation (37%) and positive family history (50%) were significantly higher in cases versus controls.
- Common features included microcephaly, short stature, hypertelorism, and various anomalies.
- A five-item checklist excluded 20% of children from further testing without missing subtelomere cases.
Conclusions:
- Prenatal onset of growth retardation and positive family history are key indicators for subtelomeric defects.
- A checklist incorporating these criteria and chromosomal phenotype features improves diagnostic rates for subtelomeric defects in intellectually disabled children.
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