CHILD syndrome belongs to the group of hereditary skin diseases called genodermatoses. It is a very rare disorder that affects only one side of the body, usually the right. In addition to genodermatosis, equilateral malformations of limbs and abnormalities of internal organs occur.
What is CHILD syndrome?
The acronym CHILD stands for “Congenital Hemidysplasia with Ichthyosiform Nevi and Limb Defects,” which is a single term used to describe the skin disorder as well as the malformations and abnormalities of limbs and internal organs. This congenital disorder was first described in 1968 by human geneticist Arthur Falek. The term was coined in 1980 by the dermatologist Rudolf Happle. It is a congenital disease that is passed on to the child in a dominant X-linked manner. Less than 60 cases have been described to date. Because of the dominant X chromosome, inheritance to the male sex is associated with lethal malformations.
Causes
Because the right side of the body is usually affected by CHILD syndrome, this condition is also known as hemiparesis syndrome. The cause is monogenic inheritance through the dominant X chromosome, with one mutation being lethal in male patients. The cause is mutations in the NSDHL gene (Xq28). Enzymes involved in cholesterol biosynthesis are affected. Cells lack this enzyme, which is important for embryonic development, resulting in a very broad spectrum of malformations.
Symptoms, complaints, and signs
CHILD syndrome is characterized by a hemifacial congenital skin disorder that belongs to the group of ichthyosiform erythroderma. The literature describes erythroderma as redness of the entire skin organ, but in this case it affects only the right side of the body. The skin shows ichthyosiform areas in mottled form (nevi) with growing, whitish-yellowish scaling, which are variably extensive and sharply demarcated. However, patchy involvement of the left side is possible. The skin manifestations are particularly pronounced in the skin folds, although the face is usually not affected. The skin is red, scaly, infiltrated and inflamed. Ichthyosis is the collective term for skin affected by cornification disorders passed on by a genetic defect. The term comes from the Greek language and means “fish”, which is why ichthyosis is also colloquially known as fish scale disease. The limbs of the affected half of the body show one or more underdeveloped extremities, characterized by shortened metacarpals of the fingers and/or toes or by missing extremities. During the first months of life, radiographs show punctate calcification (calcification) of the articular cartilages. Other abnormalities involve the central nervous system, kidneys, heart, and lungs. Possible other abnormalities include missing vertebrae, long bones and ribs. Most affected children show normal mental development, although bilateral defects of the central nervous system and brain may occur (lissencephaly). The cerebellum and spinal cord may also be affected. In isolated cases, absence of individual facial muscles, hearing loss, congenital bilateral hip deformity, and degenerative disease of the optic nerve have been described. Underdevelopment of the thyroid, adrenal glands, fallopian tubes, and ovaries is also possible.
Diagnosis and course
A differential diagnosis must be made with regard to similarly progressing disorders such as Conradi-Hünermann syndrome, Schimmelpenning-Feuerstein-Mims syndrome (nevus sebaceus), and Klippel-Trenaunay syndrome. CHILD syndrome is an exception in the group of congenital anomalies with exclusively hemiparesis, which is generally non-hereditary. According to medical experts, the general non-hereditary nature of this unilateral formation can be explained by the fact that a genetic defect that is passed down through several generations does not exclusively affect one half of the body. However, more than two-thirds of the CHILD syndromes documented to date are exclusively right-sided. Doctors suspect that a left-sided disease with strongly developed heart involvement already leads to death prenatally.The severe skin manifestations and the abnormalities and malformations of limbs and organs are a diagnostic clue, with radiographs revealing the malformations of the internal organs. An echocardiogram, ultrasonography of the internal organs, and whole-brain MRI are used to detect additional abnormalities.
Complications
As a result of CHILD syndrome, the patient suffers from significant malformations and deformities throughout the body. In most cases, this primarily affects the internal organs and limbs. There are severe restrictions of movement, so that the patient may be dependent on the help of other people in everyday life. The patient’s entire skin is reddened, which can lead to severe aesthetic discomfort. In most cases, these are also associated with depression and other mental illnesses. It is not uncommon for spots to form on the skin. Mental development is usually not affected by CHILD syndrome. However, bullying and teasing can occur, especially in children, due to the various deformities. These complaints have a negative impact on the children’s lives and can lead to behavioral problems and discomfort in adulthood. It is also not uncommon for vision and hearing to be impaired due to CHILD syndrome. In the worst case, the patient may go blind or lose hearing completely. Treatment can only be symptomatic and does not lead to further complications. Because CHILD syndrome is not fatal, symptoms can be relieved by surgical intervention.
When should you see a doctor?
If an accident or fall occurs as a result of the malformations and deformities, CHILD syndrome sufferers should go to a hospital. The pediatrician should be called if the child increasingly complains of pain, itching, and other discomfort. The characteristic redness must be closely monitored by a physician and treated if necessary. In case of inflammation or unusually severe scaling, the child should be taken to a general practitioner or dermatologist immediately. The same applies if the often occurring hip malposition causes a bad posture – in this case an orthopedist must be consulted without fail. In the case of left-sided disease, a doctor must be consulted at the first signs of cardiac arrhythmia. If depression, inferiority complexes and other psychological disorders occur as a result of the disease, psychological advice is needed. Because of the large number of possible symptoms that CHILD syndrome can cause, affected children should always see a specialist regularly. In case of severe complications, it is recommended to contact the emergency medical service.
Treatment and therapy
In female affected individuals, CHILD syndrome is not generally fatal, but it is not curable. Depending on the extent of the malformations and abnormalities, there are varying long-term prognoses. Heart and lung abnormalities are potentially fatal and require immediate surgical intervention. Renal malformations can be treated by removal of the affected organ or drainage. The affected skin areas can be alleviated by appropriate treatment and care measures. Dermatologists prefer to use urea-based preparations, which are also used to treat neurodermatitis. Topical immunomodulators such as pimecrolimus and tacrolimus have proven effective in local therapy. Long-term treatment of the diseased skin areas is carried out with emollients, which are the basis of many cosmetic and medical ointments. These are lipophilic substances that act as refatting agents to soften the skin. Ointments or lotions containing simvastatin or lovastatin in combination with cholesterol have also proved effective. Preparations containing cortisone can also alleviate the accompanying symptoms of these skin diseases. The infant’s parents have a central role in the therapy. They must guarantee compliance with the care and treatment measures, and the instructions of the attending physician must be followed without fail. Depending on the extent of skin disease and malformations, autologous skin grafts and corrective surgical procedures may be necessary. Orthopedic support devices may be helpful in cases of skeletal malformations.
Outlook and prognosis
Because CHILD syndrome is a complex of genetic malformations, the syndrome cannot be treated causally, with only symptomatic treatment available to the affected individual. A complete cure is not achieved. The further course also depends on the extent of the skin complaints, so that in some cases skin transplants may be necessary to completely alleviate the complaints. Due to the skeletal complaints, the affected persons are also dependent on assistance in everyday life. If CHILD syndrome also leads to malformations of the heart or lungs, these malformations usually lead to the death of the affected person or to a significantly reduced life expectancy. Only an immediate intervention after the birth of the patient can solve them. Mild skin disorders can also be relieved with the help of medications and creams, although lifelong therapy is necessary. Since the patient’s intelligence is not negatively affected by CHILD syndrome, ordinary mental development usually occurs. Malformations of the cerebellum can lead to hearing problems, which usually cannot be treated. In this case, they are alleviated only by a hearing aid.
Prevention
Because it is an X-linked dominant inherited disorder, expectant mothers must be screened for the presence of minimal symptoms. Furthermore, screening for an NSDHL mutation is performed. A genetic test from chorionic villus sampling will indicate whether disease is present in the embryo. Certain abnormalities can be identified by routine sonograms. There is a 50 percent chance of transmission from mother to daughter. However, inheritance to live-born male infants is not possible. Because of this initial situation, prevention in the clinical sense is not possible.
Follow-up
In CHILD syndrome, lifelong treatment and monitoring is necessary because of the symptomatology of this genetic disorder. In this respect, it does not seem quite correct to speak of follow-up. This implies a tendency to improvement, which cannot be given here. The symptoms caused by CHILD syndrome close to birth are mostly developed on one side of the body only. However, the opposite side of the body may also be affected by mild lesions. The abnormalities in multiple organ systems require constant symptomatic treatment. In addition to the already existing symptoms, further changes may occur in the course of life. These usually affect the spine or other joints. If necessary, the damaged skeleton must be supported. Due to the rarity of CHILD syndrome, treatment options are limited. In the case of organic abnormalities, surgery is often required early in life to prevent the affected person from dying. Transplantation of the skin occasionally occurs. In both cases, special follow-up care is required because the patients are usually newborns. Otherwise, treatment is symptom-oriented. If corticosteroids or immunomodulators are administered, long-term monitoring becomes necessary. This is part of the follow-up care. People who provide follow-up care for CHILD syndrome should also keep an eye out for potential exacerbations or new onset of symptoms. People affected by CHILD syndrome need lifelong support services.
Here’s what you can do yourself
Everyday life presents challenges for patients with CHILD syndrome. Depending on how pronounced the course of the disease is, several things need to be taken care of. The inflammation of the skin must be treated regularly. For this purpose, patients can use ointments or creams that are particularly fatty and contain few fragrances. The application of creams soothes the skin and makes it less sensitive. It is also important to keep the skin warm at all times. That is why patients with CHILD syndrome must not wear clothing that is too thin. Otherwise, they could quickly become chilled. If there are physical limitations due to deformities of limbs, everyday life becomes even more difficult for the patients. In many cases, however, the other half of the body is normal. Patients can therefore often perform light activities without assistance. Even driving a car is possible if the car is equipped with automatic control instead of a transmission.Other impairments such as walking or hearing, on the other hand, can be compensated for by the use of walking aids or hearing aids. Patients can specifically learn how to use such aids for their everyday lives in special therapies.
