2013
American Epilepsy Society Poster 3.276
An uncommon presentation of a mecp2 mutation: malignant migrating partial epilepsy of infancy with cataracts and upper motor neuron deficits
Authors: E. Segal, E. Fertig, S. Parisotto, H. Pedro
Rationale:
MECP2-related disorders include Rett Syndrome, atypical Rett Syndrome, and mild intellectual impairment. In these syndromes, epilepsy, psychomotor regression, and interictal electrographic abnormalities have been described. MECP2 mutations have never previously been associated with cataracts or malignant migrating partial epilepsy of infancy.
Methods:
Proband: A full-term female presented at 5 weeks of life with seizures that met International League Against Epilepsy(ILAE) criteria for malignant migrating partial epilepsy of infancy, exam findings consistent with bilateral cataracts and right-body upper motor neuron injury, was found to have a MECP2 likely disease causing mutation (identified by GeneDx, Gaithersburg, MD).
Results:
The patient has an Arg190Cys missense mutation in exon 4 of the MECP2 gene, who initially presented at 5 weeks of life having unilateral, alternating twitching of her face and extremities for 4 days. The patient was born full-term via C-section due to transverse lie. Prenatally, the patient was suspected to have bilateral cataracts. There were no neonatal complications. By 10 weeks of age, a polysomnogram diagnosed her with central sleep apnea. There is no family history of cataracts, Rett Syndrome, or epilepsy. Initially on examination, the patient was found to have bilateral cataracts, right ptosis, and right pes planus. By 20 weeks of age, the right patellar and ankle developed an asymmetric 3/4 reflex and a flattened right naso-labial fold. The patient was noted to have a head circumference deceleration within the first 6 months of life. The patient was found to have both electroclinical and subclinical focal seizures with multifocal onsets in both hemispheres (right>left). The patient’s seizures have decreased only with phenobarbital. She failed levetiracetam and oxcarbazepine due to ineffectiveness. Patient had normal plasma amino acids, urine organic acids, biochemical galactosemia and chromosome microarray analysis. Brain MRI was normal. Other genes tested in the comprehensive epilepsy panel, including SCN1A, were not found to contain disease-causing mutations. Variants of unknown significance in the TSC2 and SLC9A6 genes were also identified.
Conclusions:
This is a unique presentation for a patient with a MECP2-related disorder. In addition to an early presentation of seizures, the patient meets the ILAE criteria for malignant migrating partial epilepsy of infancy. Beyond the expected head circumference deceleration, the patient has bilateral cataracts and right ptosis with increased right lower extremity reflexes. This neurological examination is concerning for an upper motor neuron injury. The initial MRI may have been normal due to sensitivity limitations of imaging a 5 week old patient. To our knowledge, these electrographic and physical findings have not been described before. This is an example of the importance of genetic testing for the appropriate diagnosis and treatment for patients with refractory epilepsy.