Abstracts

RATIONALE: Describe the epilepsy characteristics of 1p36 monosomy syndrome in the first patient also presenting with polymicrogyria and emphasize the importance of a clinical diagnosis for genetic counseling.
METHODS: To confirm the vlinical hypothesis of monosomy 1p36 fluorescence in situ hybridization (FISH) using a subtelomeric probe 1p was used.
RESULTS: Monosomy 1p36 is a recently delineated microdeletion syndrome, characterized by moderate to severe mental retardation, growth delay, seizures and distinct cranio-facial features (large anterior fontanel, prominent forehead, horizontal eyebrows, deep set eyes, flat nasal bridge, midface hypoplasia, ear asymmetry and oro-facial clefting). Congenital heart defects are also part of the microdeletion 1p36 syndrome. Other features include hearing loss and hypothyroidism. Incidence is estimated to be 1 in 5000 births. The majority of the deletions are maternally derived. In some cases, the deletion is the result of a parental rearrangement. The deletion size is quite variable and appears to correlate with clinical complexity. Loss of the potassium channel b-subunit gene KCNAB2 has been recently reported in patients with 1p36 and intractable epilepsy.
Our patient, the first child of non-consanguineous parents presented with hypotonia at birth and was initially followed for an Ebstein anomaly. At 4 months of age, she experienced four seizures described as tonic-clonic. A month later, she developed typical infantile spasms and hypsarrhythmia. Episodes limited to an upward eye deviation were also extremely frequent. Several AEDs, including vigabatrin proved inefficient. Steroids allowed a transient control. At the age of 8 months interictal EEG showed a very slow background activity and a right temporal spike-wave focus. MRI evidenced bilateral, predominantly fronto-parietal, polymicrogyria. Complete metabolic screening was normal. A first routine chromosomal analysis was unrevealing.
The diagnosis of monosomy 1p36 was primarily suggested on the basis of a distinct pattern of facial anomalies associated with a cardiac malformation (Ebstein anomaly). Fluorescence in situ hybridization (FISH) using a subtelomeric probe 1p (Vysis) showed the lack of a signal on one chromosome 1. Parental chromosomes were normal.
CONCLUSIONS: Polymicrogyria and related disorders are not an uncommon findings in children presenting with epileptic spasms but genetic counseling is difficult on this sole element. To our knowledge this is the first reported case of polymicrogyria and spasms also presenting with 1p36 monosomy. It illustrates that although routine karyotyping may be unrevealing, the syndrome is clinically recognizable. The subsequent use of the appropriate techniques may allow a chromosomal diagnosis, rendering genetic counseling possible.