Benign nocturnal alternating hemiplegia of childhood: A clinical and nomenclatural reappraisal. (November 2018) - Maas, Roderick P.P.W.M.
Abstract: Objective: To describe the clinical spectrum of benign nocturnal alternating hemiplegia of childhood (BNAHC) including long-term follow-up data of previously published cases and to propose an underlying genetic cause of this disorder. Methods: We studied the medical data of two novel patients, reviewed the literature on BNAHC, and gathered information of the most recent follow-up of published cases regarding the course of episodes, further development, attempted drugs, ancillary investigations, and sequelae. Results: All patients, i.e. two novel cases and twelve patients identified in the literature (13 boys, 1 girl, age at onset four months to three years), experienced episodes of hemiplegia during nocturnal or daytime sleep heralded by inconsolable crying. Possible triggers included stress and sleep deprivation. Eleven of fourteen patients had a family history of migraine or 'intermittent headache' and two sets of siblings are reported. In one case, exome sequencing revealed a heterozygous 16p11.2 deletion involving 33 genes, including the PRRT2 gene. EEG showed ictal and/or interictal contralateral slowing in four patients. Treatment efficacy was generally disappointing. A complete disappearance of attacks appeared in nearly all cases at most recent follow-up. In a remarkably high number of cases (10/14, 71%), hyperactive behaviour was reported during follow-up. Conclusion: We underscore the phenotypic homogeneity including the self-limiting course of BNAHC episodes and suggest the condition be renamed 'benign childhood hemiplegia during sleep' (BCHS). We propose a role for the PRRT2 gene and the resulting neuronal hyperexcitability as one of its possible underpinning mechanisms and discuss the clinical similarities of BCHS with the recognized PRRT2 -related disorders. Highlights: Benign nocturnal alternating hemiplegia of childhood (BNAHC) is a rare, usually self-limiting entity of unknown etiology. Two novel case histories and long-term follow-up data of previously published patients are presented here. In one of our cases exome sequencing revealed a 16p11.2 deletion involving 33 genes including the PRRT2 gene. We propose a role for the PRRT2 gene and resulting neuronal hyperexcitability as one of the underpinning mechanisms of BNAHC. As hemiplegic bouts also occur during daytime naps, we suggest BNAHC be renamed "benign childhood hemiplegia during sleep.