Case series: array CGH as a tier 1 testing in diverse neurodevelopmental disorders evaluation

Case presentation: Comparative genomic hybridization based on microarrays (array CGH) is a reality in clinical practice in the neuropediatric population. It allows a high-resolution assessment of DNA copy number changes associated with chromosomal abnormalities. Objective: To highlight the importance of using the technique in the investigation of patients with diverse phenotypes. Methods: Series of case studies.

Discussion: Case 1: A 9-year-old boy with intellectual disability (ID), wide hypertelorism, wide philtrum of the nasal bridge, smooth nasolabial philtrum and shortening and fingers. CGH array showed chromosome 8 microdeletion, q23.3124.12, 2820Kb, containing 14 genes, including TRPS1, EXT1 and RAD21. Final diagnosis of Trichorhinophalangeal Syndrome type 2. Case 2: A 7-year-old boy with neurodevelopmental disorder disease (NDD), congenital clubfoot, sleep apnea, hypothyroidism and precocious pubarche. CGH with a pathogenic 4,9Mb 19p13.3p13.2 duplication. Other cases described in the literature with a similar phenotype in the same region. Case 3: A 2-year-old boy presenting with NDD and hypotonia. MRI showed agenesis of corpus callosum. CGH with a pathogenic 13q32.3 microdeletion. The older brother of the index case died with a severe form of holoprosencephaly and had the same microdeletion. Parents CGH were normal, with a suspicion of gonadal mosaicism in one of the parents causing both brothers to be affected by midline defects related to chromosome 13. Case 4: A 4-year-old boy with non-syndromic ASD. CGH evidenced duplication in the 2p25.3 region (366kb), probable pathogenic, containing MYT1L (*613084), a gene associated with neurodevelopmental disorders (NDD). Case 5: A 12-year-old girl diagnosed as cerebral palsy (CP), severe ID, refractory seizures with neurodevelopmental regression. CGH reported with a pathogenic deletion of 7.3 Mb of chromosome 2 (2q24.1q24.2), containing important genes such as SLC4A10, GCG and TBR1 (OMIM *604616) whose loss of function is associated with epilepsy and NDD.

Final comments: The use of the CGH-array is a fundamental part in the evaluation of children with ID, NDD and CP. The syndromes of microdeletions and microduplications can present with diverse phenotypes and it is up to the specialist physician to guide the family to the right diagnosis and genetic counseling.

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
18 September 2023