Rare Nephrology News

Disease Profile

CDKL5 deficiency disorder

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

CDKL5; CDKL5 disorder; Early infantile epileptic encephalopathy-2;

Summary

CDKL5 deficiency disorder is a genetic disorder that causes seizures, developmental delay, and severe intellectual disability. Seizures typically begin within a few months after birth and are difficult to control with medications. Most children have 1 to 5 seizures every day. Other symptoms include problems with sleeping, feeding, and teeth grinding. Gastrointestinal symptoms are also common and may include constipation, reflux, and air swallowing. About 1 in 5 children use a feeding tube. CDKL5 deficiency disorder occurs more often in females than males, and males usually have more severe symptoms. This disorder is caused by a change (pathogenic variant) in the CDKL5 gene that is usually not inherited from either parent (de novo). It is an X-linked dominant disorder. CDKL5 deficiency disorder was once thought to be a variant of Rett syndrome but is now considered a separate disorder.[1][2][3][4]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
1%-4% of people have these symptoms
EEG with generalized slow activity
0010845
Percent of people who have these symptoms is not available through HPO
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Broad forehead
Increased width of the forehead
Wide forehead

[ more ]

0000337
Cerebral visual impairment
0100704
Constipation
0002019
Deeply set eye
Deep set eye
Deep-set eyes
Sunken eye

[ more ]

0000490
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Epileptic encephalopathy
0200134
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Generalized myoclonic seizure
0002123
Global developmental delay
0001263
Hyperventilation
Rapid breathing
0002883
Hypsarrhythmia
0002521
Inability to walk
0002540
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Infantile spasms
0012469
Intellectual disability, profound
IQ less than 20
0002187
Multifocal seizures
0031165
Muscular hypotonia
Low or weak muscle tone
0001252
Myoclonus
0001336
Poor eye contact
0000817
Progressive microcephaly
Progressively abnormally small cranium
Progressively abnormally small skull

[ more ]

0000253
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

0011220
Scoliosis
0002650
Seizure
0001250
Short foot
Short feet
Small feet

[ more ]

0001773
Short palm
0004279
Small hand
Disproportionately small hands
0200055
Stereotypy
Repetitive movements
Repetitive or self-injurious behavior

[ more ]

0000733
Tapered finger
Tapered fingertips
Tapering fingers

[ more ]

0001182
Thick lower lip vermilion
Increased volume of lower lip
Plump lower lip
Prominent lower lip

[ more ]

0000179
X-linked dominant inheritance
0001423

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • The Epilepsy Foundation provides information on CDKL5 deficiency disorder.
    • The International Foundation for CDKL5 Research has an Introductory Guide on CDKL5 deficiency disorder that includes information on history, diagnosis, symptoms, treatments, therapies, resources, and more.
    • Genetics Home Reference (GHR) contains information on CDKL5 deficiency disorder. This website is maintained by the National Library of Medicine.
    • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

      In-Depth Information

      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 

        Selected Full-Text Journal Articles

          References

          1. Bahi-Buisson N, Bienvenu T. CDKL5-Related Disorders: From Clinical Description to Molecular Genetics. Mol Syndromol. April 2012; 2(3-5):137-152.
          2. Mangatt M, Wong K, Anderson B, et al. Prevalence and onset of comorbidities in the CDKL5 disorder differ from Rett syndrome. Orphanet Journal of Rare Diseases. 2016; 11:39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832563/.
          3. Fehr S, Wong K, Chin R, et al. Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder. Neurology. November 22, 2016; 87(21):2206-2213. https://www.ncbi.nlm.nih.gov/pubmed/27770071.
          4. Fehr S, Wilson M, Downs J, et al. The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy. Eur J Hum Genet. March 2013; 21(3):266-73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573195/.