Journal article
CHEDDA syndrome is an underrecognized neurodevelopmental disorder with a highly restricted ATN1 mutation spectrum
Clinical genetics, Vol.100(4), pp.468-477
10/2021
DOI: 10.1111/cge.14022
PMID: 34212383
Abstract
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.
Details
- Title: Subtitle
- CHEDDA syndrome is an underrecognized neurodevelopmental disorder with a highly restricted ATN1 mutation spectrum
- Creators
- Elizabeth E Palmer - UNSW SydneyChloe Whitton - UNSW SydneyMais O Hashem - King Faisal Specialist Hospital & Research CentreRobin D Clark - Loma Linda UniversitySubhadra Ramanathan - Loma Linda UniversityLois J Starr - University of Nebraska Medical CenterDanita Velasco - University of Nebraska Medical CenterJohn Karl De Dios - Dayton Children's HospitalEmily Singh - Children's Hospital of WisconsinValerie Cormier-Daire - Hôpital Necker-Enfants MaladesMaya Chopra - Boston Children's HospitalLance H Rodan - Boston Children's HospitalChristoffer Nellaker - Institute of Biomedical ScienceShenela Lakhani - MIND Research InstituteEric J Mallack - MIND Research InstituteKarin Panzer - University of Iowa Hospitals and ClinicsAlpa Sidhu - University of Iowa Hospitals and ClinicsIngrid M Wentzensen - GeneDxDidier Lacombe - Maladies Rares Génétique et Métabolisme (MRGM), U 1211 INSERM/Université de Bordeaux Bordeaux FranceVincent Michaud - Maladies Rares Génétique et Métabolisme (MRGM), U 1211 INSERM/Université de Bordeaux Bordeaux FranceFowzan S Alkuraya - King Faisal Specialist Hospital & Research Centre
- Resource Type
- Journal article
- Publication Details
- Clinical genetics, Vol.100(4), pp.468-477
- DOI
- 10.1111/cge.14022
- PMID
- 34212383
- ISSN
- 0009-9163
- eISSN
- 1399-0004
- Grant note
- MR/M014568/1 / Medical Research Council
- Language
- English
- Date published
- 10/2021
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984354150502771
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