ClinVar Genomic variation as it relates to human health

Unsteady gait (present) , Truncal titubation (present) , Seizures (present) , Recurrent upper respiratory tract infections (present) , Primary Caesarian section (present) , Poor speech (present) , Paroxysmal dystonia (present) , Paroxysmal dyskinesia (present) , Nystagmus (present) , Limb tremor (present) , Headache (present) , Episodic ataxia (present) , Dysmetria (present) , Dysarthria (present) , Difficulty walking (present) , Delayed gross motor development (present) , Delayed fine motor development (present) , Cognitive impairment (present) , Caesarian section (present) , Autistic behavior (present) , Abnormal delivery (present) (less)

Cognitive impairment (present) , Global developmental delay (present) , Seizure (present) , Intellectual disability, profound (present) , Microcephaly (present) , Short stature (present) , Autistic behavior (present) , Absent speech (present) , Reduced eye contact (present) , Aplasia/Hypoplasia of the cerebellum (present) (less)

Episodic Ataxia Type 9 In an 11-year-old boy with episodic ataxia type 9 (EA9; 618924), Liao et al. (2010) identified a de novo heterozygous c.788C-T transition in the SCN2A gene, resulting in an ala263-to-val (A263V) substitution in a highly conserved residue in the S5 segment of transdomain I. The mutation was not found in 93 controls. Electrophysiologic studies showed that the A263V mutation resulted in a 3-fold increase in persistent sodium current, indicating a profound gain of function. Other changes including slowed fast inactivation and accelerated recovery of slow inactivation. These findings were consistent with a gain-of-function effect and neuronal hyperexcitability. Schwarz et al. (2016) reported a boy (patient 3) with EA9 who carried a de novo A263V mutation in the SCN2A gene. In 2 unrelated patients with EA9, Johannesen et al. (2016) and Gorman and King (2017) independently identified a de novo A263V mutation in the SCN2A gene. Functional studies of the variant were not performed. Developmental and Epileptic Encephalopathy 11 Wolff et al. (2017) identified a de novo A263V mutation in a 13-year-old patient (patient 34) with developmental and epileptic encephalopathy-11 (DEE11; 613721). He presented at 3 weeks of age with intractable seizures. He had severely impaired intellectual development and microcephaly. Brain imaging showed atrophy and hypomyelination. He died at 13 years of age. The report expanded the phenotype associated with this mutation. Phenotypic Overlap Touma et al. (2013) reported a pair of monozygotic twin boys who carried the same de novo heterozygous A263V mutation identified in the patient reported by Liao et al. (2010). On the first day of life, both boys developed refractory seizures (up to 60 per day) associated with a burst-suppression pattern on EEG. One twin died on day 19 from iatrogenic cardiopulmonary arrest. The other twin became seizure-free on medication at age 8 months, and seizure-free without medication at age 2 years; this corresponded to improvement of the EEG abnormalities. The surviving twin showed global developmental delay; he could say short sentences but had head lag, axial hypotonia, and inability to crawl. Brain imaging of the surviving twin showed diffuse signal abnormalities in the basal ganglia and brainstem suggestive of cytotoxic edema; these abnormalities improved with age. The phenotype was reminiscent of developmental and epileptic encephalopathy-11 (613721). However, the seizure remission was also consistent with EA9, even though episodic ataxia was not reported. The surviving patient was only 2.5 years of age at the time of the report. (less)

Episodic Ataxia Type 9 In an 11-year-old boy with episodic ataxia type 9 (EA9; 618924), Liao et al. (2010) identified a de novo heterozygous c.788C-T transition in the SCN2A gene, resulting in an ala263-to-val (A263V) substitution in a highly conserved residue in the S5 segment of transdomain I. The mutation was not found in 93 controls. Electrophysiologic studies showed that the A263V mutation resulted in a 3-fold increase in persistent sodium current, indicating a profound gain of function. Other changes including slowed fast inactivation and accelerated recovery of slow inactivation. These findings were consistent with a gain-of-function effect and neuronal hyperexcitability. Schwarz et al. (2016) reported a boy (patient 3) with EA9 who carried a de novo A263V mutation in the SCN2A gene. In 2 unrelated patients with EA9, Johannesen et al. (2016) and Gorman and King (2017) independently identified a de novo A263V mutation in the SCN2A gene. Functional studies of the variant were not performed. Developmental and Epileptic Encephalopathy 11 Wolff et al. (2017) identified a de novo A263V mutation in a 13-year-old patient (patient 34) with developmental and epileptic encephalopathy-11 (DEE11; 613721). He presented at 3 weeks of age with intractable seizures. He had severely impaired intellectual development and microcephaly. Brain imaging showed atrophy and hypomyelination. He died at 13 years of age. The report expanded the phenotype associated with this mutation. Phenotypic Overlap Touma et al. (2013) reported a pair of monozygotic twin boys who carried the same de novo heterozygous A263V mutation identified in the patient reported by Liao et al. (2010). On the first day of life, both boys developed refractory seizures (up to 60 per day) associated with a burst-suppression pattern on EEG. One twin died on day 19 from iatrogenic cardiopulmonary arrest. The other twin became seizure-free on medication at age 8 months, and seizure-free without medication at age 2 years; this corresponded to improvement of the EEG abnormalities. The surviving twin showed global developmental delay; he could say short sentences but had head lag, axial hypotonia, and inability to crawl. Brain imaging of the surviving twin showed diffuse signal abnormalities in the basal ganglia and brainstem suggestive of cytotoxic edema; these abnormalities improved with age. The phenotype was reminiscent of developmental and epileptic encephalopathy-11 (613721). However, the seizure remission was also consistent with EA9, even though episodic ataxia was not reported. The surviving patient was only 2.5 years of age at the time of the report. (less)

Neonatal seizure (present) , Abnormality of vision (present) , Myopia (disease) (present) , Seizures (present) , Generalized tonic-clonic seizures (present) , Abnormality of the skin (present) , Hemangioma (present) , Allergy (present) , Drug allergy (present) , Food allergy (present) (less)