1,721,179 research outputs found
The expanding phenotype of GLUT1-deficiency syndrome
No full textTransport of glucose from the bloodstream across the blood-brain barrier to the central nervous system is facilitated by glucose transport protein type I (GLUT1), the first member of the solute carrier family 2 (SLC2). Heterozygous Mutations in the GLUT1/SLC2A1 gene, occurring de novo or inherited as in autosomal dominant trait, result in cerebral energy failure and a clinical condition termed GLUT1-deficiency syndrome (GLUT1-DS). Clinical features usually comprise motor and mental developmental delay, seizures with infantile onset, deceleration of head growth often resulting in acquired microcephaly, and a movement disorder with ataxia, dystonia, and spasticity. Subsequent to the delineation of this classic phenotype the variability of signs and symptoms in GLUT1-DS is being recognized. Patients with (i) carbohydrate-responsive symptoms, with (ii) predominant ataxia or dystonia, but without seizures, and with (iii) paroxysmal exertion-induced dyskinesia and seizures have been reported. Common laboratory hallmark in all phenotypes is the reduced glucose level in cerebrospinal fluid with lowered CSF-to-blood glucose ratio. Treatment with a ketogenic diet results in marked improvement of seizures and movement disorders. (C) 2009 Elsevier B.V. All rights reserved
Episodic Movement Disorders: From Phenotype to Genotype and Back
No full textEpisodic dyskinetic movement disorders are a heterogeneous group of rare conditions. Paroxysmal dyskinesias constitute the core of this group and usually exhibit normal interepisodic neurologic findings. Contrariwise, episodic dyskinesias occur as a particular feature of complex chronic neurologic disorders. Conjunction of accurate phenotyping with upto-date methods of molecular genetics recently provided remarkable new insights concerning the genetic causes of episodic dyskinesia. The identification of heterozygous mutations in the PRRT2 gene in paroxysmal kinesigenic dyskinesia as well as in benign familial infantile seizures linked episodic movement disorders with epilepsy. Alternating hemiplegia of childhood, the prototype of a chronic multisystem disease with episodic dyskinesia as a clinical hallmark, was recently found to be caused by heterozygous de novo mutations in the ATP1A3 gene. The clinical spectra of PRRT2 as well as of ATP1A3 mutations are still expanding. This review summarizes new genetic findings and clinical aspects in episodic dyskinesias
FOXG1 Syndrome
No full textClinical characteristics: FOXG1 syndrome is characterized by moderate-to-profound developmental delay and intellectual disability, postnatal growth deficiency, congenital or postnatal microcephaly, hyperkinetic/dyskinetic movement disorder, hypotonia, neurobehavioral/psychiatric manifestations (motor stereotypies, impairment of social interaction, abnormal sleep patterns, unexplained episodes of crying, restlessness, and bruxism), feeding difficulties with poor weight gain, strabismus, seizures, spasticity, gastroesophageal reflux, and aspiration. Some individuals have cortical visual impairment, kyphosis, scoliosis, and/or abnormal breathing. Characteristic neuroimaging findings include corpus callosum anomalies (especially a marked, filiform thinning of the rostrum of the corpus callosum), a simplified gyral pattern, and hyperplasia of the fornices.
Diagnosis: The diagnosis of FOXG1 syndrome is established in a proband with clinical and/or characteristic neuroimaging findings and a heterozygous pathogenic variant in FOXG1 identified by molecular genetic testing.
Management: Treatment of manifestations: Developmental and educational support; consideration of anti-dyskinetic pharmacotherapy; treatment for seizures by an experienced neurologist; treatment of spasticity per orthopedist; physical medicine and rehabilitation, physical therapy, and occupational therapy to help avoid contractures and falls; anti-spasmodic pharmacotherapy; feeding therapy with gastrostomy tube placement as needed; standard treatment of gastroesophageal reflux; treatment for refractive errors and strabismus per ophthalmologist; standard treatments for scoliosis; social work and family support.
Surveillance: At each visit, monitor developmental progress, educational needs, seizures, changes in tone, movement disorders, growth, nutritional status, and safety of oral intake; behavioral assessment for irritability and sleep issues; assess for evidence of gastroesophageal reflux, aspiration, and/or respiratory insufficiency; physical medicine, occupational therapy, physical therapy assessment for mobility and self-help skills; monitor for strabismus and need for low vision services per treating ophthalmologist; assess family needs.
Genetic counseling: FOXG1 syndrome is an autosomal dominant disorder typically caused by a de novo pathogenic variant. Risk to future pregnancies is presumed to be low as the proband most likely has a de novo FOXG1 pathogenic variant. There is, however, a recurrence risk to sibs based on the possibility of parental germline mosaicism. Given this risk, prenatal and preimplantation genetic testing may be considered
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