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Published on: February 21, 2015
Chromosomal Aberrations in Pediatric Patients With Moderate/Severe Developmental Delay/Intellectual Disability With
Dan Wu1, Yi Wu2, Yulong Lan3
1Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia.
Insights
Chromosome microarray (CMA) is clinically useful for diagnosing moderate to severe developmental delay/intellectual disability (DD/ID) in Chinese pediatric patients. Higher diagnostic yields were observed with increased congenital abnormalities, supporting CMA as a first-tier test.
Area of Science:
- Genetics
- Pediatrics
- Clinical Diagnostics
Background:
- Developmental delay/intellectual disability (DD/ID) and dysmorphic features are significant pediatric concerns.
- Accurate genetic diagnosis is crucial for effective management and genetic counseling.
- The utility of chromosome microarray (CMA) in specific pediatric populations requires further investigation.
Purpose of the Study:
- To evaluate the clinical usefulness of chromosome microarray (CMA) in Han Chinese pediatric patients with unexplained moderate or severe developmental delay/intellectual disability (DD/ID).
- To assess the diagnostic yield of CMA in patients with combined dysmorphic features or other congenital anomalies.
- To determine the prevalence and types of pathogenic copy number variations (pCNVs) in this cohort.
Main Methods:
- Retrospective analysis of 122 pediatric patients with unexplained moderate/severe DD/ID and/or associated features.
- Data collected from a single-center neurorehabilitation clinic in southern China.
- Chromosome microarray (CMA) analysis was performed to detect copy number variations (CNVs).
Main Results:
- Chromosome microarray (CMA) identified pathogenic copy number variations (pCNVs) in 37.7% (46/122) of patients.
- Excluding certain genetic variations, 37 patients had 39 pathogenic copy number variations (pCNVs), with a high prevalence of Angelman/Prader-Willi syndrome.
- The diagnostic yield and pCNV prevalence increased significantly with the number of congenital abnormalities present (P < 0.05).
Conclusions:
- Chromosome microarray (CMA) is a valuable tool for diagnosing genetic causes of moderate/severe DD/ID in pediatric patients.
- Implementing CMA as a first-tier test, especially in patients with congenital structural anomalies, improves diagnostic rates.
- These findings support the selective use of CMA for enhanced clinical management in affected children.
Background:
This study aimed to examine the clinical usefulness of chromosome microarray (CMA) for selective implementation in patients with unexplained moderate or severe developmental delay/intellectual disability (DD/ID) and/or combined with different dysphonic features in the Han Chinese population.
Methods:
We retrospectively analyzed data on 122 pediatric patients with unexplained isolated moderate/severe DD/ID with or without autism spectrum disorders, epilepsy, dystonia, and congenital abnormalities from a single-center neurorehabilitation clinic in southern China.
Results:
A total of 46 probands (37.7%) had abnormal CMA results among the 122 study patients. With the exclusion of aneuploidies, uniparental disomies, and multiple homozygotes, 37 patients harbored 39 pathogenic copy number variations (pCNVs) (median [interquartile range] size: 3.57 [1.6 to 7.1] Mb; 33 deletions and 6 duplications), enriched in chromosomes 5, 7, 15, 17, and 22, with a markedly high prevalence of Angelman/Prader-Willi syndrome (24.3% [nine of 37]). Three rare deletions in the regions 5q33.2q34, 17p13.2, and 13q33.2 were reported, with specific delineation of clinical phenotypes. The frequencies of pCNVs were 18%, 33.3%, 38.89%, 41.67%, and 100% for patients with 1, 2, 3, 4, and 5 study phenotypes, respectively; patients with more concomitant abnormalities in the heart, brain, craniofacial region, and/or other organs had a higher CMA diagnostic yield and pCNV prevalence (P < 0.05).
Conclusions:
Clinical application of CMA as a first-tier test among patients with moderate/severe DD/ID combined with congenital structural anomalies improved diagnostic yields and the quality of clinical management in this series of patients.
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