CDKL V Deficiency Disorder; CDKL Five Deficiency Disorder; CDKL5 Encephalopathy; CDKL V Encephalopathy; CDKL Five Encephalopathy; CDKL5-Related Epilepsy; CDKL V Related Epilepsy; CDKL5-Related Epileptic Encephalopathy; CDKL Five Related Epileptic Encephalopathy; Early Infantile Epileptic Encephalopathy 2; Early Infantile Epileptic Encephalopathy Two; Early Infantile Epileptic Encephalopathy II; Early Infantile Epilepsy Encephalopathy 2; Early Infantile Epilepsy Encephalopathy Two; Early Infantile Epilepsy Encephalopathy II

CDKL5 Deficiency Disorderis a rare X-linked genetic disorder caused by mutations in the CDKL5 gene. CDKL5 gene mutations can cause a broad range of clinical symptoms and severity. Most people with CDKL5 deficiency disorder have early-onset, intractable epilepsy and neurodevelopmental delay affecting cognitive, motor, speech, and visual functioning. CDKL5 is one of the most common forms of genetic epilepsy

Diagnostic testing:The diagnosis of CDKL5 Deficiency disorders is made by:

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  History and physical examination;

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  Genetic testing for CDKLF mutations;

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  Electroencephalography (EEG) testing; and

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  Magnetic resonance imaging (MRI).

Physical findings: The signs and symptoms of CDKL5 Deficiency disorders may include:

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  Seizures;

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  Microcephaly (small head size);

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  Hand wringing movements or mouthing of hands;

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  Global developmental delays and intellectual delays;

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  Impaired language/communication skills;

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  Hypersensitivity to touch;

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  Lack of eye contact or poor eye contact;

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  Gastroesophageal reflux (GERD);

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  Constipation;

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  Small, cold feet;

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  Breathing irregularities, such as hyperventilation;

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  Grinding of teeth;

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  Episodes of crying or laughing for no reason;

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  Low/poor muscle tone;

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  Limited hand skills;

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  Autistic-like tendencies, such as hand flapping;

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  Scoliosis;

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  Cortical visual impairment (CVI);

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  Apraxia;

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  Eating/drinking challenges;

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  Interruptive sleep;

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  Sideways glance; and

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  Crossing of the legs.

ICD-9: 345.1

Seizures in CDKL5 deficiency disorder usually begin within the first 3 months of life, and they can appear as early as the first week after birth. The types of seizures change with age, and they usually follow a predictable pattern. Seizures occur daily in most affected individuals, and they are resistant to treatment.

About 90% of people diagnosed with CDKL5 deficiency disorder are female. Affected males tend to have more severe developmental disabilities, including profound intellectual disability and almost no development of gross and fine motor skills. The life expectancy varies depending on the severity of health problems.

Currently there is no cure for CDKL5 deficiency disorder. Management is mainly focused on optimizing the individual’s abilities and providing psychosocial support for the family. Anticonvulsant drugs, ketogenic diets, and vagus nerve stimulation are used to treat seizures. Steroids and adrenocorticotrophic (ACTH) have been used for the treatment of infantile spasms.

Suggested MER for Evaluation:

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  Clinical history and examination that describes the diagnostic features of the impairment;

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  Genetic testing confirming mutations in the CDKL5 gene; and

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  MRI of the brain.

Suggested Listings for Evaluation: