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GeneReviews((R))-/-? 1993[]; ? (?): ? PMID41343687show ga
CLINICAL CHARACTERISTICS: TAF8-related neurodevelopmental disorder (TAF8-NDD) is characterized by brain malformations, microcephaly, severe-to-profound global developmental delays, and often epilepsy. Clinical features may present initially in utero with fetal growth restriction and possibly brain anomalies seen on prenatal imaging. TAF8-NDD is a progressive neurodegenerative condition, with progressive global cerebral and cerebellar atrophy and grossly enlarged ventricles. Both gray and white matter are affected. Motor development is severely impaired in all affected individuals, initially marked by axial hypotonia in infancy, followed by progressive spasticity of the upper and lower limbs during childhood and adolescence. Clinically, this progression is characterized by increasing spasticity, a reduction in spontaneous movements, and the development of epilepsy in most individuals. No reported affected individual has achieved the ability to sit independently, ambulate, or use verbal language skills. All affected individuals have severe-to-profound intellectual disability. Other reported features include developmental regression, severe visual impairment, and feeding difficulties (dysphagia, gastroesophageal reflux disease) that may warrant placement of a feeding tube. DIAGNOSIS/TESTING: The diagnosis of TAF8-NDD is established in a proband with suggestive findings and biallelic pathogenic variants in TAF8 identified by molecular genetic testing. MANAGEMENT: Treatment of manifestations: Standardized treatment with anti-seizure medication by an experienced neurologist for epilepsy. Feeding therapy for poor growth with low threshold for gastrostomy tube placement for persistent feeding issues and/or dysphagia. Standard treatment for developmental delay / intellectual disability, spasticity, contractures, gastroesophageal reflux disease, and low vision. Surveillance: At each visit, measurement of growth parameters; evaluation of nutritional status and safety of oral intake; monitor for signs/symptoms of gastroesophageal reflux disease, evidence of aspiration, and respiratory insufficiency; monitor for new manifestations such as seizures, changes in tone, and regression of skills; monitor developmental progress and educational needs; and assess mobility. Two to three years after original brain MRI, consider repeat brain MRI to assess for evidence of cerebral atrophy. Ophthalmology evaluation per treating clinician. GENETIC COUNSELING: TAF8-NDD is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a TAF8 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the TAF8 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.
GeneReviews((R))-/-? 1993 ; ? (?): ?
