What is CHILD Syndrome?
CHILD syndrome is a rare inherited disease that can affect different parts of the body. The name CHILD is an acronym for “Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects.” This syndrome was first documented by Dr. Otto Sachs in 1903, and there have been other similar cases reported since then.
The disorder, which is mostly found in females, is linked to the ‘X’ sex chromosome and can have serious consequences for males. The syndrome likely develops as a result of changes in the gene that makes a protein called NSDHL, causing it to behave abnormally or not at all. This protein is necessary because it helps transform a molecule called 3-β-hydroxysteroid dehydrogenase.
In turn, this molecule plays a significant role in creating cholesterol, a substance essential for many body functions. Cholesterol, for instance, forms a vital part of cell membranes that protect cells and help them function. It is also needed to produce hormones that control many aspects of our health, such as glucocorticoids, mineralocorticoids, and sex hormones. Additionally, cholesterol is critical in myelin, a substance that facilitates nerve impulse transmission, which helps nerve cells send signals quickly.
You might suspect CHILD syndrome in a newborn if, during a physical examination, you find anything resembling a skin condition on one side of the newborn’s body. This condition can also be associated with other symptoms such as one-sided limb defects and skin lesions, a type of red, scaly skin called ichthyosiform erythroderma, variable skin inflammation, and congenital heart disease. The syndrome is found in about 1 in 100,000 live births.
What Causes CHILD Syndrome?
CHILD syndrome is a condition that is passed down through family lines in a way that’s linked to the X chromosome. This is referred to as X-linked dominant inheritance. This means that a single copy of the altered gene in each cell can cause the disorder and that it affects typically females because they usually have two X chromosomes.
The syndrome is due to a mutation, or change, in a gene on the X chromosome known as NSDHL. This gene is responsible for creating an enzyme involved in cholesterol production in the body. Different types of mutations in the NSDHL gene have been found, all of which lead to the gene not working properly.
Some research suggests that the symptoms of CHILD syndrome, which often appear on one side of the body (unilateral), could be due to problems with a biological signaling pathway during early development in the womb. This could be due to issues with cholesterol processing. Also, another gene has been mentioned as a possible cause of CHILD syndrome in some people. This gene, called EBP, also plays a key part in the body’s production of cholesterol.
Risk Factors and Frequency for CHILD Syndrome
CHILD syndrome is a rare medical condition, with fewer than 100 cases reported so far. It usually proves fatal for males during pregnancy, which means that most of the patients diagnosed with CHILD syndrome are females.
- The disorder is typically passed down in families through an X-linked dominant pattern, but its inheritance can be complex. There have been instances reported where the condition varies inside the womb.
- In an unusual case, a male diagnosed with CHILD syndrome was found to have a normal chromosomal pattern known as 46 XY karyotype. Experts suggest he may have experienced an early change in his cells, called a somatic mutation.
- Signs of CHILD syndrome are usually clearly visible at the time of birth and continue to be present throughout a patient’s life.
Signs and Symptoms of CHILD Syndrome
CHILD syndrome refers to a condition with symptoms that usually become noticeable at birth, affecting various body systems and organs on one side. The most common sign is red, thickened skin with yellowish scales that often affect the right side of the body more than the left. This abnormal skin condition tends to be limited to one side and mostly spares the face.
In some cases, symptoms might not be obvious at birth and may appear until as late as 9 years old. There are other skin-related issues that someone with CHILD syndrome may also have, which may involve:
- Unilateral body fold involvement
- Verruciform xanthomas (yellowish patches or nodules of fatty tissue)
- Onychodystrophy (nail deformities)
- Scarring hair loss
As the child grows, less redness but more skin thickening and body-fold involvement in these areas are observed. These skin symptoms can be seen in 30 to 79 percent of all patients.
Patients with CHILD syndrome may also have issues with their limbs on the same side as their skin lesions. These can range from minor contractions to underdevelopment or even complete absence of a limb. These abnormalities could cause problems like scoliosis (curvature of the spine) or difficulty moving. An X-ray finding referred to as “epiphyseal stippling” is common and found in 80 to 99 percent of cases of CHILD syndrome. However, this usually disappears as the child gets older.
If present, any cardiovascular and neurological malformations are also typically on the same side as the skin abnormalities. The presence of these malformations may lead to early death.
Testing for CHILD Syndrome
Medical tests that evaluate sterol, a type of lipid found in cells, can help identify abnormalities in a protein involved in steroid production. These abnormalities are found through unusually high levels of specific sterol intermediates. Various imaging tests such as x-rays, ultrasound, CT scans, and MRIs are also performed to look for issues with the bones or organs. Detecting these issues early can help doctors take action in a timely manner.
DNA testing can further help confirm a diagnosis by identifying a defect in a specific gene, NSDHL. A skin biopsy can also be performed. During this biopsy, your doctor will take a small sample of your skin and examine it under a microscope, looking for specific changes in cells that indicate the disease, such as fat-filled cells in the skin layers. Even though this condition affects how the body processes cholesterol, people with this syndrome usually have normal cholesterol levels.
Treatment Options for CHILD Syndrome
When it comes to treating CHILD syndrome, a rare genetic condition, your treatment plan will depend on your specific symptoms and needs.
If your symptoms are primarily skin-related, there are a variety of treatments that can help. For localized symptoms, which only appear in certain areas, a cream or gel called tretinoin may be applied to the skin. If the symptoms are more widespread, systemic retinoids, or medications that help regulate growth and cell reproduction, might be considered.
However, the effectiveness of certain treatments like corticosteroids (medications that reduce inflammation) and emollients (moisturizers that soothe and hydrate the skin) isn’t entirely clear, even though they are often used in combination with other treatments to possibly enhance the overall results.
Some other options to treat skin symptoms use specific medications called lovastatin, simvastatin, and ketoconazole. They work by improving the skin’s cholesterol levels and by inhibiting certain enzymes involved in cholesterol production.
In the case of CHILD syndrome, it’s important to deal with other health issues that might come up due to the condition. As it can affect the body in a number of ways, you might need to see multiple specialists depending on your symptoms.
For example, if you have problems with your limbs, you might need to see an orthopedic surgeon who specializes in the body’s musculoskeletal system. They’ll be able to help correct any existing issues, and work to prevent further complications.
In the case of heart abnormalities, a pediatric cardiologist would need to be involved, particularly for children, as they specialize in children’s heart health.
For any neurological symptoms, a neurologist would be the appropriate specialist to go to. Since CHILD syndrome often causes multiple different types of symptoms, it’s important to treat the whole person, not just individual symptoms. This might look like a team of specialists working together, including a dermatologist to help manage the skin problems from the syndrome.
What else can CHILD Syndrome be?
If your doctor suspects your child has CHILD syndrome, they might also consider other conditions that can have similar indicators. These include:
- Epidermal nevus (skin growths)
- Sebaceous nevus (skin color anomalies)
- Inflammatory linear verrucous epidermal nevus (ILVEN – a type of skin condition)
- Phacomatosis pigmentokeratotica (skin pigment disorder)
- X-linked dominant chondrodysplasia punctata (a disorder of skeletal development)
An in-depth medical check-up can help identify whether the child does have CHILD syndrome or if they might be suffering from one of these other conditions.
What to expect with CHILD Syndrome
The skin symptoms of CHILD syndrome often get better as the patient gets older. However, the condition can be more severe for patients whose symptoms appear on the left side of their body. This is because these patients are more likely to also have abnormalities in their internal organs, which can complicate their condition.
If a patient with CHILD syndrome also has problems with their nervous system, lungs, or heart, this can make their overall condition worse. These additional health problems can make the prognosis or expected outcome of the condition less favorable.
Possible Complications When Diagnosed with CHILD Syndrome
The complications a child with CHILD syndrome experiences depends on which parts of their body are affected. A few adults with this genetic condition, for example, one woman aged 33, have developed a type of skin cancer known as squamous cell carcinoma. The skin abnormalities seen in CHILD syndrome can also make children more prone to infections.
Certain complications can affect their physical abilities. For instance, minor skeletal abnormalities might not cause many problems. However, if a child is born without a limb or with severely underdeveloped limbs, it could lead to spine curvature (scoliosis), difficulty moving, and limited hand skills.
CHILD syndrome may also create problems with the heart. This can range from a hole in the wall of the heart (septal defects) to only having one coronary artery or one ventricle, instead of two. Some heart problems can be so severe that a baby might not survive beyond its first few weeks. Alternatively, those with less severe heart conditions might find physical activities, like sports, difficult as they grow up.
Brain-based issues are not always a feature of CHILD syndrome. However, some children might have problems with their hearing or sight, or they might struggle with cognitive tasks. In one case, a premature baby girl who was born with a range of brain abnormalities linked to CHILD syndrome sadly passed away soon after she was born.[35]
There have also been reports of varying severity of problems with other organs in the body, including the lungs, ovaries, fallopian tubes, and thyroid. The earlier these complications are detected and treated, the better a child with CHILD syndrome will likely fare.[36]
Recovery from CHILD Syndrome
The type of after-surgery care and recovery process depends on the type of surgery done and the age of the patient. For example, younger patients who have undergone surgery for issues related to the brain, heart, and lungs might need to spend a long time in intensive care after the operation, and they may also require a long rehabilitation period. However, older patients with issues that don’t involve vital internal organs, are more likely to heal and be able to go back to their regular routines quicker.
Preventing CHILD Syndrome
If a family is affected by CHILD syndrome, it’s crucial for them to have genetic counseling. This counseling is a means of explaining to parents and patients how the condition is passed down through genes and what the chances are of it being passed to future generations. If a family is thinking about having more children, they may have the option to go through prenatal testing and counseling. Scientists are continuously researching possible treatments that could target the genetic defect causing the condition. At this time, there are no specific ways to prevent NSDHL mutations, which cause CHILD syndrome.