Isaac Disease: Does the Clinical Spectrum Include White Matter Disease in the Brain? (P05.160)

Abstract

Objective: Presenting the phenotypic variability of hereditary Issac9s Syndrome. Background Isaac syndrome is a disorder of peripheral nerve hyperexcitability (PNH) manifesting as myokymia, muscle cramps, and neuromyotonia. It is considered to be an acquired condition with antibodies directed against voltage-gated potassium channels. More recently, hereditary cases have been described in association with episodic ataxia and benign familial neonatal epilepsy. These pedigrees have exhibited a wide phenotypic spectrum even within families with the same mutations. Until now, mutations in KCNA1 and KCNQ2 have been described in hereditary cases of Isaacs syndrome. In patients with KCNA1, neuromyotonia occurs in association with episodic ataxia and skeletal deformities. KCNQ2 mutations were initially identified in patients with benign familial neonatal epilepsy but now, peripheral nerve hyperexcitability may also occur. There are also cases of hereditary Issacs syndrome described without the presence of an identifiable mutation in either gene. We describe a three-generation family with inherited Issacs syndrome. Design/Methods: Case Report. Results: In the first 2 generations features of peripheral nerve hyperexcitability was present, and in the third generation refractory epilepsy is described in a child. The proband also has white matter changes on MRI resembling demyelinating disease. Cerebrspinal fluid studies show normal levels of IgG and oligoclonal bands. Abnormal MRI findings have not been described in Isaac syndrome before. Conclusions: The spectrum of abnormalities for Isaac syndrome may include central nervous system white matter disease, cognitive dysfunction, in addition to seizures and peripheral nerve disease with muscle spasm, twitching, and hypetrophy. Patients with white matter disease and recurrent muscle spasm and hypertrophy may be included in the spectrum of antibody mediated central nervous system disorders, such as Isaac syndrome. Family history of other neurological disease may provide important clues as to the cause of such symptoms. Disclosure: Dr. Sedarous has nothing to disclose. Dr. Lange has nothing to disclose.