CDKL5-deficiency disorder

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ORPHA:505652OMIM:300672G40.4
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1FDA treatments5Active trials25Specialists8Treatment centers

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UniteRare data is sourced from FDA.gov, ClinicalTrials.gov, Orphanet, OMIM, and NORD.
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Overview

CDKL5 deficiency disorder (CDD), sometimes called CDKL5 disorder or early-onset seizure variant of Rett syndrome, is a rare brain condition caused by changes (mutations) in the CDKL5 gene. This gene gives the body instructions for making a protein that is important for normal brain development and function. When this protein does not work properly, it leads to serious problems with brain activity. The condition mainly affects babies and young children. The most noticeable sign is seizures that start very early in life, often in the first few months. These seizures can be very hard to control, even with multiple medications. Children with CDD also have significant developmental delays, meaning they may not reach milestones like sitting, walking, or talking at the expected ages. Many children have very limited or no ability to speak and need help with daily activities throughout their lives. Other common features include problems with muscle tone (muscles may be too floppy or too stiff), difficulty with hand use, vision problems, sleep disturbances, and gastrointestinal issues like constipation. While there is currently no cure, treatments focus on managing seizures and supporting development through therapies. Research into targeted treatments is actively ongoing, giving families reason for hope.

Also known as:

Key symptoms:

Frequent and hard-to-control seizures starting in early infancySevere intellectual disabilityLittle or no ability to speakDifficulty or inability to walk independentlyPoor muscle tone (floppy muscles) or stiff musclesLimited purposeful hand useVision problems or difficulty tracking objects with the eyesSleep disturbances and irregular sleep patternsConstipation and other digestive problemsRepetitive hand movements or hand wringingBreathing irregularitiesScoliosis (curved spine) in some childrenFeeding difficulties, especially in infancy

Clinical phenotype terms (50)— hover any for plain English
Generalized tonic seizureHP:0010818BruxismHP:0003763Abnormal muscle toneHP:0003808
Inheritance

X-linked dominant

Carried on the X chromosome; a single copy can cause the condition

Age of Onset

Infantile

Begins in infancy, roughly 1 month to 2 years old

Orphanet ↗OMIM ↗NORD ↗

FDA & Trial Timeline

8 events
Jun 2026Double-blind, Randomized, Placebo-controlled Trial of Ganaxolone in CDKL5 Deficiency Patients 6 Months to Less Than 2 Years Old

Immedica Pharma AB — PHASE3

TrialNOT YET RECRUITING
May 2026A Multicenter Open-label Phase II Study of Cemiplimab Plus Chemotherapy, Selected on the Basis of Baseline Cytidine Deaminase Activity, in Advanced Squamous Non-small Cell Lung Cancer

Gruppo Oncologico Italiano di Ricerca Clinica — PHASE2

TrialNOT YET RECRUITING
Apr 2024Targeting the Gut to Improve Seizure Control in CDKL5 Deficiency Disorder (CDD)

University of Milan — NA

TrialRECRUITING
Sep 2022Observational Study in Patients With Cyclin-dependent Kinase-like 5 Deficiency Disorder

Loulou Foundation

TrialACTIVE NOT RECRUITING
Mar 2022A Study to Investigate the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder

Zogenix, Inc. — PHASE3

TrialACTIVE NOT RECRUITING
Feb 2021International CDKL5 Clinical Research Network

University of Colorado, Denver

TrialRECRUITING
Apr 2019Dose-Escalation Study of E7727, an Oral Cytidine Deaminase Inhibitor With Oral Decitabine in Subjects With Solid Tumors

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins — PHASE1

TrialACTIVE NOT RECRUITING
Dec 2018International CDKL5 Registry

University of Pennsylvania — NA

TrialRECRUITING

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Treatments

1 available

Ztalmy

ganaxolone· Marinus PharmaceuticalsOrphan Drug

Treatment of seizures associated with CDKL5-deficiency disorder (CDD) in patients 2 years of age and older. Ganaxolone is a neuroactive steroid GABAA receptor modulator.

Clinical Trials

5 recruitingView all trials with filters →
Phase 31 trial
A Study to Investigate the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder
Phase 3
Active
PI: UCB Cares (001 844 599 2273) · Sites: Birmingham, Alabama; Los Angeles, California +44 more · Age: 135 yrs
N/A2 trials
International CDKL5 Registry
N/A
Actively Recruiting
PI: Dan Lavery, PhD (Director, CDKL5 Program of Excellence, Orphan Dise) · Sites: Philadelphia, Pennsylvania
Targeting the Gut to Improve Seizure Control in CDKL5 Deficiency Disorder (CDD)
N/A
Actively Recruiting
PI: Aglaia Vignoli, MD (University of Milan) · Sites: Milan · Age: 350 yrs
Other2 trials
Observational Study in Patients With Cyclin-dependent Kinase-like 5 Deficiency Disorder
Active
· Sites: Los Angeles, California; Aurora, Colorado +21 more · Age: 055 yrs
International CDKL5 Clinical Research Network
Actively Recruiting
PI: Timothy A Benke, MD PhD (University of Colorado, Denver) · Sites: Los Angeles, California; Aurora, Colorado +7 more · Age: 0100 yrs

Specialists

25 foundView all specialists →
TP
Timothy A Benke, MD PhD
AURORA, CO
Specialist
PI on 1 active trial
IH
Isabel Haviland
LOS ANGELES, CA
Specialist
2 CDKL5-deficiency disorder publications
AQ
Anita Quigley
WHITEHALL, PA
Specialist
2 CDKL5-deficiency disorder publications
TB
Tim A Benke
AURORA, CO
Specialist
3 CDKL5-deficiency disorder publications
SD
Scott Demarest
AURORA, CO
Specialist
4 CDKL5-deficiency disorder publications
HO
Heather E Olson
Specialist
4 CDKL5-deficiency disorder publications
HL
Helen Leonard
Specialist
2 CDKL5-deficiency disorder publications
NB
Nicole J Van Bergen
Specialist
2 CDKL5-deficiency disorder publications
SM
Sean Massey
Specialist
2 CDKL5-deficiency disorder publications
JC
John Christodoulou
Specialist
2 CDKL5-deficiency disorder publications
EP
Elia Pestana-Knight
Specialist
2 CDKL5-deficiency disorder publications
JW
Judith L Weisenberg
SAINT LOUIS, MO
Specialist
2 CDKL5-deficiency disorder publications
EM
Eric D Marsh
Specialist
2 CDKL5-deficiency disorder publications
BZ
Bo Zhang
Specialist
2 CDKL5-deficiency disorder publications
JD
Jenny Downs
Specialist
1 CDKL5-deficiency disorder publication
TB
Timothy A Benke
AURORA, CO
Specialist
2 CDKL5-deficiency disorder publications
AM
Alan K Percy, MD
BIRMINGHAM, AL
Specialist
PI on 2 active trials1 CDKL5-deficiency disorder publication
OM
Orrin Devinsky, MD
NEW YORK, NY
Specialist
PI on 4 active trials
DM
Dennis J Dlugos, MD
PHILADELPHIA, PA
Specialist
PI on 2 active trials
LM
Liankun Ren, MD
Specialist
PI on 4 active trials1 CDKL5-deficiency disorder publication
JP
Jeffrey L Neul, MD, PhD
NASHVILLE, TN
Specialist
PI on 2 active trials
AM
Aglaia Vignoli, MD
Specialist
PI on 1 active trial1 CDKL5-deficiency disorder publication
JM
Joseph Hulihan, MD
NEWTOWN, PA
Specialist
PI on 2 active trials
DP
Dan Lavery, PhD
Philadelphia, Pennsylvania
Specialist

Rare Disease Specialist

PI on 1 active trial
PB
Paula Bokesch
LEXINGTON, MA
Specialist
PI on 1 active trial

Treatment Centers

8 centers
⚗️ Trial Site

Washington University

📍 St Louis, Missouri

👤 Sawa M Ito, MD, PhD

👤 Anthony A. Amato, MD

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

Travel Grants

No travel grants are currently matched to CDKL5-deficiency disorder.

Search all travel grants →NORD Financial Assistance ↗

Community

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Latest news about CDKL5-deficiency disorder

Disease timeline:

New recruiting trial: Targeting the Gut to Improve Seizure Control in CDKL5 Deficiency Disorder (CDD)

A new clinical trial is recruiting patients for CDKL5-deficiency disorder

New recruiting trial: International CDKL5 Clinical Research Network

A new clinical trial is recruiting patients for CDKL5-deficiency disorder

New trial: Immune Disorder HSCT Protocol

Phase PHASE2 trial recruiting. Transplant preparative regimen of alemtuzumab, fludarabine, thiotepa, and melphalan

New trial: International CDKL5 Registry

Phase NA trial recruiting. Survey Instrument

Caregiver Resources

NORD Caregiver Resources

Support, advocacy, and financial assistance for caregivers of rare disease patients.

Mental Health Support

Rare disease caregiving can be isolating. Connect with counseling and peer support.

Family & Caregiver Grants

Financial assistance programs specifically for caregivers of rare disease patients.

Social Security Disability

Learn how rare disease patients may qualify for SSDI/SSI benefits.

Questions for your doctor

Bring these to your next appointment

  • Q1.What anti-seizure medications do you recommend starting with, and what is the plan if they do not work?,Should we consider the ketogenic diet, and how would we get started safely?,What therapies (physical, occupational, speech) should my child be receiving, and how often?,Are there any clinical trials for CDD that my child might be eligible for?,What signs should prompt me to call emergency services or use a rescue medication?,How often should my child be monitored for complications like scoliosis or vision problems?,What support services and patient organizations are available to help our family?

Common questions about CDKL5-deficiency disorder

What is CDKL5-deficiency disorder?

CDKL5 deficiency disorder (CDD), sometimes called CDKL5 disorder or early-onset seizure variant of Rett syndrome, is a rare brain condition caused by changes (mutations) in the CDKL5 gene. This gene gives the body instructions for making a protein that is important for normal brain development and function. When this protein does not work properly, it leads to serious problems with brain activity. The condition mainly affects babies and young children. The most noticeable sign is seizures that start very early in life, often in the first few months. These seizures can be very hard to control,

How is CDKL5-deficiency disorder inherited?

CDKL5-deficiency disorder follows a x-linked dominant inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does CDKL5-deficiency disorder typically begin?

Typical onset of CDKL5-deficiency disorder is infantile. Age of onset can vary across affected individuals.

Are there clinical trials for CDKL5-deficiency disorder?

Yes — 5 recruiting clinical trials are currently listed for CDKL5-deficiency disorder on UniteRare. See the clinical trials section on this page for phase, sponsor, and site details sourced from ClinicalTrials.gov.

Which specialists treat CDKL5-deficiency disorder?

25 specialists and care centers treating CDKL5-deficiency disorder are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.