TY - JOUR
TI - The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy
AU - Fehr, S.
AU - Wilson, M.
AU - Downs, J.
AU - Williams, S.
AU - Murgia, A.
AU - Sartori, S.
AU - Vecchi, M.
AU - Ho, G.
AU - Polli, R.
AU - Psoni, S.
AU - Bao, X.
AU - De Klerk, N.
AU - Leonard, H.
AU - Christodoulou, J.
JO - European Journal of Human Genetics: EJHG
PY - 2013
VL - 21
TODO - 3
SP - 266-273
PB - 
SN - 1018-4813, 1476-5438
TODO - 10.1038/ejhg.2012.156
TODO - cyclin dependent kinase;  cyclin dependent kinase like 5;  methyl CpG binding protein 2;  unclassified drug, adolescent;  article;  birth;  child;  developmental disorder;  female;  gene mutation;  human;  major clinical study;  male;  onset age;  preschool child;  priority journal;  Rett syndrome;  school child;  seizure;  sleep disorder, Abnormalities, Multiple;  Adolescent;  Age of Onset;  Child;  Child, Preschool;  Face;  Female;  Hand;  Humans;  Infant;  Logistic Models;  Male;  Methyl-CpG-Binding Protein 2;  Mutation;  Protein-Serine-Threonine Kinases;  Rett Syndrome;  Seizures;  Young Adult
TODO - 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. © 2013 Macmillan Publishers Limited All rights reserved.
ER -