Introduction:
In children with CDKL5 deficiency disease, the onset of seizures often occurs within the first three months of life, but they can arise as early as one week after birth. The different forms of seizures that might occur alter with age and may follow a pattern clinicians can foresee. Aberrant muscular contractions characterize tonic seizures; epileptic spasms, which involve short episodes of muscle jerks; and generalized tonic-clonic seizures, which entail a loss of consciousness, muscle rigidity, and convulsions, are the most common types of seizures. Even while persons with CDKL5 deficient conditions can experience times when they are seizure-free, the majority of those who have the disorder experience seizures daily. In most cases, treatment does not reduce or eliminate seizures caused by CDKL5 deficiency disease.
In the past, CDKL5 deficient condition was regarded as an unusual variant of Rett syndrome. These disorders share symptoms, the most notable of which include convulsions, intellectual impairment, and a variety of other difficulties with development. However, the indications and symptoms of CDKL5 deficiency disorder and its genetic cause differ from those of Rett syndrome. As a result, CDKL5 deficiency disorder is now considered a separate illness.
What Is the Frequency of CDKL5 Disorder?
CDKL5 deficiency disorder is rare, affecting only one in 40,000 to 60,000 newborns. About 90 percent of people with CDKL5 deficiency disorder are female.
What Are the Signs and Symptoms Exhibited by the Child With CDKL5 Disorder?
The characteristic symptoms are:
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Children who suffer from CDKL5 deficiency condition typically have delayed development.
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The majority have a severe kind of intellectual disability and have little or no speaking.
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Development of gross motor abilities, such as sitting, standing, and walking, is either delayed or not achieved in the individual.
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Roughly one-third of those who have been afflicted are capable of walking unassisted. Fine motor abilities, such as picking up small things with the fingers, are also hindered; around half of those affected have purposeful use of their hands at some point throughout their illness.
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The majority of persons who have this illness also have issues with their vision (cortical visual impairment).
The clinical signs that can be seen are:
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Some people with this condition sometimes have trouble breathing.
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Some people with CDKL5 deficiency disorder have:
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A high, broad forehead, large.
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Deep-set eyes.
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Larger philtrum (midline groove in the upper lip).
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Fuller lips.
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Widely spaced teeth and a high roofed palate.
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Other physical differences can also happen, such as an unusually small head (microcephaly), a spine that curves from side to side (scoliosis), and fingers that are tapered.
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What Are the Causes of CDKL5 Disorder?
CDKL5 deficiency disorder is caused by changes in the CDKL5 gene, as the name suggests. These changes are also called mutations. This gene tells the body how to make a protein needed for the brain to grow and work properly. Changes in the CDKL5 gene can lower the amount of working CDKL5 protein or change how it works in nerve cells (neurons). A lack of CDKL5 or a problem with how it works can alter brain development, but it is unclear how these changes lead to the symptoms of CDKL5 deficiency disorder.
How Is CDKL5 Disorder Diagnosed?
The diagnosis is based on physical signs and symptoms, confirmed by molecular genetic testing for CDKL5 mutations or a multigene panel test for early-onset epilepsy. Some CDKL5 mutations and variants do not cause disease but seem benign. The mutation is considered disease-causing to confirm a diagnosis according to well-known guidelines for determining pathogenicity.
What Are the Therapies Given for CDKL5 Disorder?
People with CDKL5 are mostly treated for their symptoms and supported by doctors. A multidisciplinary team approach is the most effective way to provide necessary treatments to make the most of a person's skills and help them learn new ones. Early intervention therapies like physical therapy, occupational therapy, and speech and communication therapy should be given more attention.
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Dietary Intervention: Maintaining good nutritional status requires the participation of a dietician with competence in managing individuals with severe intellectual disabilities. Some affected patients can consume food orally, but the majority require enteral nutritional support.
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Speech Therapy: As the majority of individuals with CDKL5 do not develop verbal, expressive language, additional modes of communication, such as communication boards, technical devices, and switch-activated systems, should be examined to promote decision-making and environmental access.
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Seizure Control: Controlling seizures is challenging and often the most complex health problem to deal with. No anticonvulsant has been found to work for everyone, and people often need to take more than one. Ganaxolone was approved in 2022 to treat seizures in people at least two years old.
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Surgical Intervention for Ortho Problems: Many people with this disorder also have scoliosis, but there is little information about how common it is or how long it lasts, like there are many other symptoms. Some people may be told to wear a brace, while others will need to have surgery.
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Physiotherapy: Physiotherapy and physical therapy can also help improve overall muscle tone, trunk stability, strength, and balance, prevent foot deformities, keep the foot in the proper position, and keep heel cords from shortening.
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Other Therapies: Another treatment that has helped some people is vagal nerve stimulation (VNS). Dietary changes like the ketogenic diet have demonstrated varying effectiveness in some people. However, these strict dietary adjustments can be burdensome for families because they must only be carried out under close medical supervision.
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Genetic and Psychological Counseling: It is suggested for families with a child with the condition.
Conclusion:
The International CDKL5 Disorder database was set up in September 2012, and it still collects information from families worldwide with the child who has this disorder. This database lets a person gather essential information that will help them learn more about this disorder and the health problems it causes. To educate about these mutations and be able to give families some information about the projected clinical course for their child, further research is now being done to study the characteristics of the few mutations that are shared by more than one family.
