Chapter 41 - 4p (Wolf–Hirschhorn) syndrome

Summary

Wolf-Hirschhorn syndrome (WHS) is a multiple congenital anomalies/intellectual disability disorder due to deletion, or loss of material, of the distal portion of the short arm of chromosome 4. Seizures/epilepsy represents one of the main clinical challenges in 4p WHS. Epilepsy is well controlled in most WHS individuals (80%). Phenobarbital has been reported as the most effective drug against tonic-clonic seizures. About 30-40% of the deletions will not be detected by karyotype. Therefore, fluorescence in situ hybridization (FISH) with cosmid probes from the WHS critical region (WHSCR), or comparative genomic hybridization microarray (aCGH) are necessary to confirm the diagnosis. Brain magnetic resonance imaging (MRI) should be performed in all individuals with seizures, since malformation of the cerebral cortex may modify prognosis and management. A waking/sleeping video-EEG-polygraphic study, electrocardiogram [ECG], surface electromyogram [EMG]) is recommended in infancy and childhood, in order to achieve the best characterization of seizures.