Spectrum of epilepsy and electroencephalogram patterns in Wolf-Hirschhorn syndrome: Experience with 87 patients

To define the spectrum of epilepsy in Wolf-Hirschhorn syndrome (WHS) better, we studied 87 patients (54 females, 33 males; median age 5.6 years; age range 1-25.6 years) with confirmed 4p16.3 deletion. On the basis of clinical charts, we retrospectively analyzed the evolution of the electroencephalogram (EEG) findings and seizures. Epilepsy occurred in 81 patients (93%) within the first 3 years of life. Sixty out of 81 (74%) had generalized tonic-clonic seizures, which was the only seizure pattern in 32. Tonic spasms occurred in 15 out of 81 (18%), complex partial seizures in 10 out of 81 (12%), and clonic seizures in 6 out of 81 (7%). Seizures were frequently triggered by fever (59 out of 81; 73%), and occurred in clusters in 36 out of 72 (50%). In the same 36 (50%), unilateral or generalized clonic or tonic-clonic status epilepticus occurred during the first 3 years of life. Twenty-seven out of 81 patients (33%) developed atypical absences between 1 and 6 years, accompanied by a myoclonic component involving the eyelids and the hands. Distinctive EEG abnormalities were observed in 73 out of 81 (90%). Epilepsy was well controlled in 65 out of 81 (81%), mainly with valproate and phenobarbital, and improved with age in all. Thirty-two out of 58 (55%) are currently seizure-free. Seizures stopped at a median age of 4 years 6 months. Epilepsy represents a major clinical challenge in WHS; however, it has a good prognosis. Early diagnosis and treatment of atypical absences, subtle and often misdiagnosed, is mandatory.