Classical West "syndrome" phenotype with a subtelomeric 4p trisomy

Area of Science:

• Genetics
• Neurology
• Pediatrics

Background:

• West syndrome, characterized by infantile spasms, is often diagnosed as idiopathic.
• Genetic factors can contribute to West syndrome, but are not always apparent in initial assessments.

Observation:

• A girl presented with infantile spasms and mild intellectual disability, initially diagnosed with idiopathic West syndrome.
• Despite successful treatment with adrenocorticotropic hormone (ACTH), mild dysmorphic features prompted further investigation.
• Parental karyotyping revealed a balanced paternal translocation (4p;17q), leading to partial 4p trisomy in the proband.

Findings:

• The proband had an undetected cytogenetic anomaly (partial 4p trisomy) associated with transient hypsarrhythmia.
• This contrasts with typical chromosomal abnormalities in West syndrome, which usually present with severe outcomes.
• The patient exhibited a milder clinical course and good neurological outcome post-treatment.

Implications:

• Suggests the need for systematic telomeric screening in patients diagnosed with "idiopathic" West syndrome, especially those with mild intellectual disability and subtle dysmorphic features.
• Highlights the importance of considering genetic etiologies even when initial karyotypes are normal.
• This case broadens the understanding of genotype-phenotype correlations in West syndrome.