Epilepsia, 44(9):1183–1190, 2003 Blackwell Publishing, Inc. C  2003 International League Against Epilepsy Electroclinical Patterns and Evolution of Epilepsy in the 4p– Syndrome ∗ Domenica Battaglia, ‡Giuseppe Zampino, †Marcella Zollino, ∗ Paolo Mariotti, ∗ Celeste Acquafondata, ∗ Donatella Lettori, ∗ Marika Pane, ‡Isabella Vasta, †Giovanni Neri, ∗ Charlotte Dravet, and ∗ Francesco Guzzetta Departments of ∗ Child Neurology and Psychiatry and †Medical Genetics, ‡Institute of Pediatrics, Catholic University, School of Medicine, Rome, Italy Summary: Background: Wolf–Hirschhorn syndrome (WHS) is a well-known clinical entity caused by partial deletion of the short arm of one chromosome 4 (4p– syndrome). Seizures oc- cur in almost all the cases, but studies on the electroclinical disorder and its evolution are still scarce. We present a longi- tudinal study of the electroclinical features in 10 children with WHS. Methods: Ten patients (five boys and five girls) underwent a detailed clinical assessment and a prolonged EEG study. Six of the 10 also had video-polygraphy. Results: Nine of the 10 patients had seizures; they were gen- eralized or unilateral clonic and tonic–clonic, and atypical ab- sences associated with myoclonic jerks. Age at onset of seizures varied from 1 day to 2.5 years. In all the patients, including the only one without seizures, two stereotyped EEG patterns were observed, consisting of (a) bursts of rhythmic (3–5 Hz), high-voltage slow waves located in the posterior regions and in- creased by sleep, or bursts of rapid spike–wave complexes in the centroparietal and parietooccipital regions; and (b) repetitive rapid posterior spikes. Sleep organization was constantly absent or very poor. The evolution of epilepsy was frequently good, with four seizure-free cases at the end of follow-up, two of them weaned from antiepileptic drugs (AEDs). Conclusions: Seizure onset in WHS also can occur at neonatal age. At least two electrical stereotyped patterns of the epileptic disorder are associated with a relevant disorganization of the sleep states. Prognosis of epilepsy is generally good both for the seizure control and for its evolution. Key Words: Wolf– Hirschhorn syndrome—Electroclinical patterns—Epileptic evolution. Wolf–Hirschhorn syndrome (WHS) is a well-known clinical entity caused by partial deletion of the short arm of one chromosome 4 (4p– syndrome). Clinical manifes- tations include a typical craniofacial appearance with mi- crocephaly, hypertelorism, large and protruding eyes, high nasal bridge, short philtrum, and micrognathia, associated with major malformations (congenital heart defects, mid- line defects, and renal and skeletal anomalies), intrauterine and postnatal growth retardation, and neurologic abnor- malities (hypotonia, mental retardation, and epilepsy). Seizures occur in practically all the cases (1–3). Only a few studies have reported electroclinical features (4– 10) in WHS, stressing the similarities to EEG findings in Angelman syndrome (AS) (8). Several points concerning the mechanism of seizures, their age at onset, and their evolution, however, have not been investigated. Accepted May 2, 2003. Address correspondence and reprint requests to Professor F. Guzzetta at Department of Child Neurology and Psychiatry, Catholic University Medical School, Rome 00168, Italy. E-mail: fguzzetta@rm.unicatt.it We report the results of a serial electroclinical study of 10 patients with WHS. PATIENTS AND METHODS Our series consists of 10 patients (five boys and five girls) with partial deletion of the short arm of chromo- some 4. Prometaphase chromosome analysis (600–800 bands) was performed on peripheral lymphocyte by the R(RBG) banding method. A minimum of 20 metaphases were scored in each patient. Fluorescent in situ hy- bridization (FISH) analysis was carried out in all pa- tients with the subtelomeric probe pC847.351 and with probes 190b4 and 174g8, delimiting, distally and prox- imally, the first defined WHS critical region (WHSCR) (10,11). The proximal breakpoint of the deletion varied from p15.1 to p16.2. By FISH, the deletion was demon- strated to be terminal, and to include the WHSCR on each occasion. The newly defined critical region, WHSCR-2 (12), also was included in the deletion interval in all patients. 1183