A characteristic electroclinical pattern is described in a child with Pitt-Rogers-Danks syndrome (PRDS) and in 14 reports of Wolf-Hirschorn syndrome (WHS) reviewed at the Division of Medical Genetics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Both syndromes are caused by deletions of the short arm of chromosome 4.

A 13 month-old female child presented with persistent growth failure and developmental delay. She could not sit and exhibited stereotyped hand-wringing movements. Dysmorphic features included a triangular face, prominent eyes, hypertelorism, and micrognathia. A relative macrocephaly (50th percentile) contrasted with a height and weight below the 3rd percentile. At reevaluation at 3 years, the developmental level was at 18 months, and she had tonic and generalized myoclonic seizures, controlled by valproate. In video-EEG recordings, 2-3 Hz high-voltage spike-wave bursts were associated with myoclonic jerks, and some without clinical manifestations. The bursts were localized over the centro-occipital area and became diffuse and generalized in sleep. The parents karyotypes were normal. [1]

COMMENT. Wolf-Hirschhorn syndrome (WHS) is characterized by severe growth and psychomotor retardation, microcephaly, dysmorphic triangular facies (“Greek helmet” appearance), skeletal and cardiac defects. Pitt-Rogers-Danks syndrome (PRDS) shares features like microcephaly, growth and mental retardation, but is less severe than WHS, without skeletal and cardiac anomalies. Both syndromes are caused by 4p deletions. Seizures occur in the majority of patients reported, and the EEG findings appear to be characteristic and common to both syndromes, and similar to those in Angelman’s syndrome (AS). Periodic bursts of 2-3 Hz high-voltage slow waves with spike wave activity are typically biparietal and associated with myoclonic jerks in sleep in WHS and PRDS, and are usually bifrontal or generalized in AS. Most cases of AS are caused by deletions on chromosome 15qll-13, involving GABA receptor genes. Other GABA receptor genes have been mapped to chromosome 4p. Electroclinical and genetic similarities in WHS and AS suggest a common epileptic mechanism involving GABA pathways. The EEG might be of value in early diagnosis of these syndromes.