The GABRB3 gene encodes the β3 subunit of the γ-aminobutyric acid (GABA) _A receptor, and its mutation causes developmental and epileptic encephalopathy. Intractable focal epilepsy associated with a characteristic interictal EEG pattern started at 2 months of age in a female pediatric patient who exhibited a novel de novo GABRB3 variant, NM_000814.5:c.778C＞A:p. (Leu260Met). Her epilepsy was characterized by multifocal onset seizures with rare migrating foci. The seizures were refractory but were suppressed at 15 months of age by the administration of potassium bromide (KBr), and she is currently seizure-free at 4 years and 5 months of age. Although her development had been stagnant during the active epilepsy period, it progressed after seizure termination ; she became able to sit by herself before 19 months and stand without support at 35 months of age. The interictal EEG continued to show unique multifocal spikes and prominent fast activity, which was observed before treatment was initiated and remarkably intensified in amplitude even after seizure suppression. We believe that her EEG pattern, which contained a large amount of fast activity, was characteristic, and we speculated that such unusual fast activity might be related to dysfunction of the GABA system associated with the GABRB3 variant. This is the first report on the efficacy of KBr in GABRB3-related epilepsy, and it suggests a treatment option for this intractable epilepsy.

  Camurati-Engelmann disease (MIM : 131300) is a rare autosomal dominant skeletal dysplasia characterized by cortical thickening and fusiform enlargement of the diaphysis of the long bones caused by gain-of-function variants in the transforming growth factor-β1 (TGFB1) gene. Most patients present with muscle weakness, waddling gait and easy fatigability in early childhood, followed by bone symptoms, such as limb pain, after adolescence. We report two boys who were initially suspected of having neuromuscular disease but were later diagnosed with Camurati-Engelmann disease in early childhood. Their perinatal courses and early gross motor development were normal. Both patients developed a waddling gait shortly after they achieved walking at the age of 12 and 14 months, respectively. They were referred to our hospital because they exhibited Gowers sign at the 3-year-old medical examination. Although serum CK values and electromyography were normal, routine skeletal muscle imaging studies (CT, MRI) revealed bone lesions. Plain X-ray of the lower limb demonstrated bone involvement characteristic of Camurati-Engelman disease. The diagnosis was confirmed by identification of a missense variant (NM_000660.7 : c.652C＞T [p.Arg218Cys], rs104894721) in the TGFB1 gene in both patients. In one patient, treatment with losartan was initiated at the age of 3 years, which improved exercise capacity. Camurati-Engelmann disease should be considered in children with proximal muscle weakness. When no specific neuromuscular disease can be identified in children with muscle weakness, physicians should perform skeletal muscle CT or MRI examination of lower limbs to evaluate the bone involvement.