Neuropediatrics 2005; 36 - V16
DOI: 10.1055/s-2005-867975

Breakage of the ERBB4-gene in a girl with reciprocal translocation t(1;2) (p22.3;q34) – Is there a relation to severe infantile epilepsy?

E Maier 1, PM Kroisel 2, L Claes 3, P De Jonghe 3, M Mach 4, E Petek 4, B Plecko 1
  • 1Univ.- Klinik für Kinder- und Jugendheilkunde, Ambulanz für Neuropädiatrie und angeborene Stoffwechselerkrankungen, Graz
  • 2Humangenetisches Institut, Universität Greifswald, Abteilung für klinische Genetik, Greifswald
  • 3Born- Bunge Foundation, University of Antwerp, Department of Molecular Genetics, Antwerp
  • 4Medizinische Universität Graz, Institut für Biologie und Humangenetik, Graz

We report on a now 4 ½ year old female patient, who has been suffering from severe epilepsy from the age of 6 weeks onward. Beside mild hypertrichosis no stigmata or dysmorphic signs were detected. Cranial imaging, routine CSF analysis and biochemical screening for amino- and organoacidopathies were normal. Seizures initially were therapyresistant to pyridoxine, phenobarbitone and valproate but by age 3 years could be controlled by a low dose combination of valproate, clonazepam and topiramate. Developmental delay was evident from early infancy with marked delay of motor milestones and severe mental retardation. At the age of 4 years she had poor visual contact, absent speech, insensitivity to pain and generalized dyspraxia. Mild muscular hypotonia with scoliotic posture of the upper spine was present, deep tendon reflexes were preserved. EEG showed a monomorphic pattern of rhythmic high-voltage alpha/theta activity with lack of fronto-occipital differentiation and of epileptic discharges. Motor nerve conduction velocity as well as cranial MRI were normal.

Chromosomal analysis including BAC-FISH revealed a reciprocal t(1;2) (p22.3;q34) translocation, leading to breakage of a single gene (ERBB4- gene) on chromosome 2, while on chromosome 1 no gene was located close to the breakpoint. The human ERBB4-gene consists of 28 exons and spans a genomic region of about 1.15 Mb. The gene product is a transmembrane receptor tyrosine kinase, involved in neuronal cell proliferation and differentiation. To further investigate the relevance of our single case findings the ERBB4-gene was analyzed in another 47 patients with epileptic encephalopathy of unknown origin. Exons and flanking introns of the ERBB4- gene were analyzed by direct sequencing. Aside from polymorphisms no disease causing mutations could be identified in this cohort of patients.

Further studies are pending to investigate the role of ERBB4-gene mutations in severe infantile epilepsies.