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. 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

Scott T Demarest  1   2   3   4   5 , Heather E Olson  6 , Angela Moss  2 , Elia Pestana-Knight  7   8   9 , Xiaoming Zhang  7   8   9 , Sumit Parikh  9   10 , Lindsay C Swanson  6 , Katherine D Riley  6 , Grace A Bazin  6 , Katie Angione  1   3 , Lisa-Marie Niestroj  11 , Dennis Lal  7   9   11   12   13   14 , Elizabeth Juarez-Colunga  2   15 , Tim A Benke  1   3   4   5   16   17
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CDKL5 deficiency disorder: Relationship between genotype, epilepsy, cortical visual impairment, and development

Scott T Demarest et al. Epilepsia. 2019 Aug.

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.

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Conflict of interest statement

Disclosures of Conflicts of Interest

Dr. Demarest has consulted for Upsher Smith and BioMarin on subject matter unrelated to this project and sits on the advisory board for the SLC6A1 Connect family foundation. Dr. Benke has consulted for IFCR, LouLou foundation, Marinus, Avexis, Takeda, Ovid, Adadia and Neuren. Dr. Olson has consulted for Takeda. All other authors have no conflicts of interests or disclosures.

Figures

Figure 1:
Figure 1:
Multivariable Linear Regression Model
See this image and copyright information in PMC

Comment in

  • Phenotype to Genotype and Back Again.
    Mefford HC. Mefford HC. Epilepsy Curr. 2020 Feb 17;20(2):88-89. doi: 10.1177/1535759720901734. eCollection 2020 Mar-Apr. Epilepsy Curr. 2020. PMID: 32313504 Free PMC article. No abstract available.

References

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