Clinical and genetic analysis of a family with two rare reflex epilepsies.

PURPOSE: To determine clinical phenotypes, evolution and genetic background of a large family with a combination of two unusual forms of reflex epilepsies. METHOD: Phenotyping was performed in eighteen family members (10 F, 8 M) including standardized EEG recordings with intermittent photic stimulation (IPS). Genetic analyses (linkage scans, Whole Exome Sequencing (WES) and Functional studies) were performed using photoparoxysmal EEG responses (PPRs) as affection status. RESULTS: The proband suffered from speaking induced jaw-jerks and increasing limb jerks evoked by flickering sunlight since about 50 years of age. Three of her family members had the same phenotype. Generalized PPRs were found in seven members (six above 50 years of age) with myoclonus during the PPR. Evolution was typical: Sensitivity to lights with migraine-like complaints around adolescence, followed by jerks evoked by lights and spontaneously with dropping of objects, and strong increase of light sensitivity and onset of talking induced jaw jerks around 50 years. Linkage analysis showed suggestive evidence for linkage to four genomic regions. All photosensitive family members shared a heterozygous R129C mutation in the SCNM1 gene that regulates splicing of voltage gated ion channels. Mutation screening of 134 unrelated PPR patients and 95 healthy controls, did not replicate these findings. CONCLUSION: This family presents a combination of two rare reflex epilepsies. Genetic analysis favors four genomic regions and points to a shared SCNM1 mutation that was not replicated in a general cohort of photosensitive subjects. Further genetic studies in families with similar combination of features are warranted.

[A 9-year-old boy with sudden memory loss]. / Een 9-jarige jongen met plotseling geheugenverlies.

BACKGROUND: Transient global amnesia is a recognised phenomenon in adults. However in children it is rarely described. It is characterised by a sudden loss of memory in an otherwise healthy patient. What is striking is that other cognitive functions and neurological examination are normal. CASE DESCRIPTION: A 9-year-old boy presented at the paediatric ward with acute onset retrograde and anterograde amnesia. He had no history of headache or other (neurological) symptoms. There were no known emotional or physical stressors. A general physical and neurological examination showed no abnormalities. The boy was hospitalised for observation overnight. The next day he was fully recovered. CONCLUSION: Transient global amnesia may occur in childhood. Since patients recover spontaneously, watchful waiting is justified.