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Epilepsia. 2019 Aug;60(8):1733-1742. doi: 10.1111/epi.16285. Epub 2019 Jul 16.

CDKL5 deficiency disorder: Relationship between genotype, epilepsy, cortical visual impairment, and development.

Demarest ST1,2,3,4,5, Olson HE6, Moss A2, Pestana-Knight E7,8,9, Zhang X7,8,9, Parikh S9,10, Swanson LC6, Riley KD6, Bazin GA6, Angione K1,3, Niestroj LM11, Lal D7,9,11,12,13,14, Juarez-Colunga E2,15, Benke TA1,3,4,5,16,17.

Author information

1
Children's Hospital Colorado, Aurora, Colorado.
2
Adult and Child Consortium for Health Outcomes Research and Delivery Science, Aurora, Colorado.
3
University of Colorado School of Medicine, Aurora, Colorado.
4
Department of Pediatrics, Colorado School of Public Health, Aurora, Colorado.
5
Department of Neurology, Colorado School of Public Health, Aurora, Colorado.
6
Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, Massachusetts.
7
Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio.
8
Department of Neurology, Lerner Research Institute, Cleveland, Ohio.
9
Genomic Medicine Institute, Lerner Research Institute, Cleveland, Ohio.
10
Department of Neurogenetics, Lerner Research Institute, Cleveland, Ohio.
11
Cologne Center for Genomics, University of Cologne, Cologne, Germany.
12
Cleveland Clinic Children's, Cleveland, Ohio.
13
Stanley Center for Psychiatric Research, Cambridge, Massachusetts.
14
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts.
15
Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado.
16
Department of Pharmacology, Colorado School of Public Health, Aurora, Colorado.
17
Department of Otolaryngology, Colorado School of Public Health, Aurora, Colorado.

Abstract

OBJECTIVE:

The cyclin-dependent kinase like 5 (CDKL5) gene is a known cause of early onset developmental and epileptic encephalopathy, also known as CDKL5 deficiency disorder (CDD). We sought to (1) provide a description of seizure types in patients with CDD, (2) provide an assessment of the frequency of seizure-free periods and cortical visual impairment (CVI), (3) correlate these features with genotype and gender, and (4) correlate these features with developmental milestones.

METHODS:

This is a cohort study of patients with CDD. Phenotypic features were explored and correlated with gene variant grouping and gender. A developmental score was created based on achieving seven primary milestones. Phenotypic variables were correlated with the developmental score to explore markers of better developmental outcomes. Multivariate linear regression was used to account for age at last visit.

RESULTS:

Ninety-two patients with CDD were seen during the enrollment period. Eighteen were male (19%); median age at last visit was 5 years (interquartile range = 2.0-11.0). Eighty-one percent of patients developed epileptic spasms, but only 47% of those also had hypsarrhythmia. Previously described hypermotor-tonic-spasms sequence was seen in only 24% of patients, but 56% of patients had seizures with multiple phases (often tonic and spasms). Forty-three percent of patients experienced a seizure-free period ranging from 1 to >12 months, but only 6% were still seizure-free at the last visit. CVI was present in 75% of all CDD patients. None of these features was associated with genotype group or gender. CVI was correlated with reduced milestone achievement after adjusting for age at last visit and a history of hypsarrhythmia.

SIGNIFICANCE:

The most common seizure types in CDD are epileptic spasms (often without hypsarrhythmia) and tonic seizures that may cluster together. CVI is a common feature in CDD and is correlated with achieving fewer milestones.

KEYWORDS:

CDKL5 deficiency disorder; cortical visual impairment; hypermotor-tonic-spasms sequence; hypsarrhythmia; spasms

PMID:
31313283
DOI:
10.1111/epi.16285

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