Wolf-Hirschhorn syndrome: a case with normal karyotype, demonstrated by array CGH (aCGH)

Area of Science:

• Genetics
• Molecular Biology
• Clinical Genetics

Background:

• Wolf-Hirschhorn syndrome (WHS) is a rare genetic disorder characterized by distinctive facial features, developmental delay, intellectual disability, and seizures.
• Diagnosis of WHS can be challenging, particularly when conventional karyotype analysis appears normal.

Observation:

• A 27-month-old girl presented with classic clinical manifestations of WHS.
• Her initial karyotype analysis was normal, despite significant clinical suspicion for a chromosomal abnormality.

Findings:

• Array comparative genomic hybridization (aCGH) revealed a 1.7 Mb microdeletion at chromosome 4q16.3-q15.3.
• This microdeletion was identified in DNA extracted from the patient's peripheral blood.

Implications:

• This case highlights the importance of advanced molecular cytogenetic techniques for diagnosing chromosomal abnormalities.
• Array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH) are crucial for evaluating patients with suspected chromosomal disorders and normal karyotypes.
• Accurate diagnosis through molecular methods can guide appropriate clinical management and genetic counseling for WHS patients.