Coexistence of fixation-off sensitivity and inverted fixation-off sensitivity in a female child with Panayiotopoulos syndrome: Video-electroencephalography documentation.

Fixation-off sensitivity (FOS) is a rare phenomenon elicited by elimination of central vision and fixation, which even in the presence of light induces occipital paroxysms or generalized paroxysmal discharges. It is most commonly encountered in patients with idiopathic childhood occipital epilepsies but may also be observed in cases of symptomatic focal and generalized epilepsies. We describe a female Emirati child with Panayiotopoulos syndrome who exhibited FOS in addition to the reverse phenomenon called "inverted fixation-off sensitivity," in which the electroencephalographic discharges were suppressed by the absence of central vision or fixation and activated by central vision or fixation.

Clinical and molecular analysis of a novel COLQ missense mutation causing congenital myasthenic syndrome in a Syrian family.

BACKGROUND: Congenital myasthenic syndromes with end-plate acetylcholinesterase deficiency are rare autosomal recessive disorders characterized by onset of the disease in early childhood, general weakness exacerbated by exertion, ophthalmoplegia, and refractoriness to anticholinesterase drugs. To date, all reported cases have been attributed to mutations in 18 genes including the COLQ gene that encodes a specific collagen that anchors acetylcholinesterase at the basal lamina of the neuromuscular junction. We identified a Syrian family with two children of consanguineous parents from two branches affected with congenital myasthenic syndrome with end-plate acetylcholinesterase deficiency. METHOD: The absence of acetylcholinesterase antibodies was demonstrated biochemically. Consequently, all the coding regions, exon-intron boundaries, and the 5' and 3' untranslated regions of the COLQ gene were amplified and sequenced using the Sanger sequencing method. RESULTS: We observed that the severity of the phenotype in the two affected children differed. One child had mild symptoms that included difficulties in gait and feeding with mild respiratory insufficiency. Her sibling died in the first months of life because of severe respiratory failure. The second patient had severe symptoms from birth and has been mechanically ventilated. DNA sequencing revealed a novel homozygous single nucleotide substitution mutation (c.1010T>C) in the COLQ gene in both patients. This substitution leads to a missense amino acid substitution at position 337 of the protein (p.Ile337Thr). This mutation is likely to impair ColQ's trimeric organization and therefore its anchoring within the synaptic basal lamina. CONCLUSION: We identified the molecular cause underlying congenital myasthenic syndrome in two patients. The marked phenotypic variation suggests that other factors including modifier genes may affect the severity of this disease.

Novel KCNQ2 mutation in a large Emirati family with benign familial neonatal seizures.

Mutations in voltage-gated potassium channel Kv7.2 are responsible for benign familial neonatal seizures type 1, a rare monogenic autosomal dominant inherited epilepsy syndrome. We describe a novel mutation (c.1126_1127delA) in exon 9 of KCNQ2, the gene encoding for the Kv7.2 channel, in a large Emirati family with benign familial neonatal seizures type 1. The mutation leads to a frameshift at amino acid position 376, triggering loss of function and haploinsufficiency. Patients with this mutation manifest repeated clonic seizures with normal interictal electroencephalograms and favorable prognoses. Signs occur within the first days of age, lingering well into puberty. KCNQ2 mutation screening, alongside genetic counseling, should be included in diagnostic evaluations of neonatal epileptic patients, potentially sparing the need for unnecessary investigations and treatment. To our knowledge, this report is the first of a KCNQ2 mutation in an Emirati family with benign familial neonatal seizures type 1.