CHEDDA syndrome is an underrecognized neurodevelopmental disorder with a highly restricted ATN1 mutation spectrum
| Autor: | Fowzan S. Alkuraya, Eric J. Mallack, Ingrid M. Wentzensen, John Karl de Dios, Subhadra Ramanathan, Robin D. Clark, Alpa Sidhu, Mais Hashem, Valérie Cormier-Daire, Maya Chopra, Danita Velasco, Shenela Lakhani, Lois J. Starr, Emily Singh, Didier Lacombe, Karin Panzer, Chloe Whitton, Elizabeth E. Palmer, Vincent Michaud, Lance H. Rodan, Christoffer Nellåker |
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| Přispěvatelé: | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2021 |
| Předmět: |
Male
Pediatrics medicine.medical_specialty Developmental delay Intellectual disability Nerve Tissue Proteins 03 medical and health sciences Epilepsy Exon 0302 clinical medicine Atrophy Neurodevelopmental disorder Genetics Medicine Missense mutation Humans Genetic Predisposition to Disease Global developmental delay Genetics (clinical) Genetic Association Studies 030304 developmental biology Arthrogryposis 0303 health sciences business.industry Facies Genomics Syndrome medicine.disease Rare diseases 3. Good health Phenotype Neurodevelopmental Disorders Child Preschool Mutation Female medicine.symptom business [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology 030217 neurology & neurosurgery |
| Zdroj: | Clinical Genetics Clinical Genetics, Wiley, 2021, 100 (4), pp.468-477. ⟨10.1111/cge.14022⟩ |
| ISSN: | 1399-0004 0009-9163 |
| DOI: | 10.1111/cge.14022⟩ |
| Popis: | We describe the clinical features of nine unrelated individuals with rare de novo missense or in-frame deletions/duplications within the « HX motif » of exon 7 of ATN1. We previously proposed that individuals with such variants should be considered as being affected by the syndromic condition of congenital hypotonia, epilepsy, developmental delay, and digital anomalies (CHEDDA), distinct from dentatorubral-pallidoluysian atrophy (DRPLA) secondary to expansion variants in exon 5 of ATN1. We confirm that the universal phenotypic features of CHEDDA are distinctive facial features and global developmental delay. Infantile hypotonia and minor hand and feet differences are common and can present as arthrogryposis. Common comorbidities include severe feeding difficulties, often requiring gastrostomy support, as well as visual and hearing impairments. Epilepsy and congenital malformations of the brain, heart, and genitourinary systems are frequent but not universal. Our study confirms the clinical entity of CHEDDA secondary to a mutational signature restricted to exon 7 of ATN1. We propose a clinical schedule for assessment upon diagnosis, surveillance, and early intervention including the potential of neuroimaging for prognostication. |
| Databáze: | OpenAIRE |
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