Chromosome 15q Structural Variants Associated with Syndromic Autism Spectrum Disorder: Clinical and Genomic Insights from Three Case Reports in a Brazilian Reference Center.

This study looked at three Brazilian children with autism who also had genetic changes on chromosome 15. Each child had different genetic changes and different additional health problems like seizures, intellectual disability, or muscle weakness. The researchers used several genetic tests to identify these changes. The findings show that chromosome 15 problems can cause autism along with other health issues, and genetic testing can help doctors better understand and treat each child's specific needs.

This Brazilian case report describes three patients with autism spectrum disorder (ASD) and chromosome 15q structural variants. Case 1 had an 8.4 Mb triplication at 15q11.2-q13.1 with epilepsy and developmental delays. Case 2 presented a 418 kb duplication at 15q13.3 with intellectual disability and speech apraxia. Case 3 showed maternal uniparental disomy consistent with Prader-Willi syndrome, manifesting hypotonia and seizures.

All cases underwent comprehensive genetic testing including chromosomal microarray analysis and methylation assays. The findings demonstrate diverse pathogenic mechanisms involving chromosome 15q in syndromic ASD and highlight the importance of genomic profiling for diagnosis and individualized care planning.

Findings support comprehensive genetic testing for patients with syndromic ASD, particularly involving chromosome 15q structural variants. Results emphasize need for individualized care planning based on specific genetic findings and associated comorbidities. Genetic counseling and multidisciplinary management approaches are indicated for affected families.

Very small sample size (n=3) limits generalizability. Case report design provides descriptive data only without controls or statistical analysis. Phenotypic characterization appears limited to clinical observations without standardized assessment tools. Long-term outcomes not reported.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition often associated with genetic syndromes. Structural variants on the long arm of chromosome 15 (15q) are recurrently implicated in syndromic ASD, yet their phenotypic spectrum remains insufficiently characterized in diverse populations. We retrospectively analyzed clinical and molecular data from three patients with ASD treated at a Brazilian public reference center who also presented neurological and systemic comorbidities. Genetic investigations included G-banded karyotyping, chromosomal microarray analysis (CMA), methylation assays, and multiplex ligation-dependent probe amplification (MLPA) when indicated.

Variants were classified according to ACMG guidelines and correlated with individual phenotypes. Case 1 showed an 8.4 Mb triplication at 15q11.2-q13.1 encompassing,, and, which are associated with epilepsy, delayed neuropsychomotor development, and dysmorphic traits. Case 2 presented a 418 kb duplication at 15q13.3 involvingand, a variant of uncertain significance correlated with intellectual disability, speech apraxia, and self-injurious behavior. Case 3 demonstrated extensive loss of heterozygosity at 15q11.2-q13.1 and 15q21.3-q26.2, which is compatible with maternal uniparental disomy and Prader-Willi syndrome, manifesting hypotonia, seizures, and global delay.

These findings underscore the potential involvement of the 15q region in syndromic ASD and related neurological comorbidities, highlighting the diverse pathogenic mechanisms and the importance of comprehensive genomic profiling for diagnosis, counseling, and individualized care.