title: The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy.
abstract: The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.
authors.affiliation: Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fehr
authors.forename: Meredith
authors.initials: M
authors.lastname: Wilson
authors.forename: Jenny
authors.initials: J
authors.lastname: Downs
authors.forename: Simon
authors.initials: S
authors.lastname: Williams
authors.forename: Alessandra
authors.initials: A
authors.lastname: Murgia
authors.forename: Stefano
authors.initials: S
authors.lastname: Sartori
authors.forename: Marilena
authors.initials: M
authors.lastname: Vecchi
authors.forename: Gladys
authors.initials: G
authors.lastname: Ho
authors.forename: Roberta
authors.initials: R
authors.lastname: Polli
authors.forename: Stavroula
authors.initials: S
authors.lastname: Psoni
authors.forename: Xinhua
authors.initials: X
authors.lastname: Bao
authors.forename: Nick
authors.initials: N
authors.lastname: de Klerk
authors.forename: Helen
authors.initials: H
authors.lastname: Leonard
authors.forename: John
authors.initials: J
authors.lastname: Christodoulou
mesh_terms: D000015:Abnormalities, Multiple / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005145:Face / Q000002:abnormalities; D005260:Female; D006225:Hand / Q000503:physiopathology; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015518:Rett Syndrome / Q000453:epidemiology / Q000235:genetics; D012640:Seizures / Q000235:genetics; D055815:Young Adult
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human