De-Grouchy syndrome is a malformation complex of which several subtypes exist. The multiple malformations are caused by deletions on chromosome 18. Patients are treated symptomatically only.
What is de Grouchy syndrome?
The so-called malformation syndromes are a group of disorders that manifest as a complex of different malformations. One subset of this group of disorders is the so-called De-Grouchy syndrome, which is divided into two distinct types with different symptoms. The first description of De-Grouchy syndrome from a scientific point of view was in 1963, and slightly more than 100 cases have been documented since the first case description. The first type of the syndrome is considered a severe form and is associated with numerous symptoms, most notably decreased muscle tone, malformations of the hands, autoimmune symptomatology, and cardiac abnormalities. Type II of the syndrome is somewhat milder and is not associated with organic malformations, for example. Instead, lead symptomatic short stature is present in this type. The two syndromes are sometimes grouped together as deletion syndromes of chromosome 18 because they result from deleting mutations of this chromosome. A mixture of the two subtypes is present in the so-called 18-R syndrome. The expression of the syndromes can be extremely variable and depends on the length of the chromosomal deletion in the individual case.
Causes
The cause of all forms of de Grouchy syndrome is a genetic mutation associated with familial clustering. In all disorders of the group, chromosome 18 is affected by deletions. Parts of the chromosome have thus been deleted, which explains the individual symptoms of the syndromes. Thus, partial monosomies underlie all forms of the syndrome. In this type of numerical chromosomal aberration, individual chromosomes are missing. In the case of De Grouchy syndrome, the monosomies relate to chromosomal segments in gene locus 18q23. For example, chromosome 18 contains genes that code for the glycoprotein APCDD1 in DNA. In addition, genes coding for the metabolic regulator Bcl-2 of mitochondria to ischemic conditions are included. Furthermore, certain genes of the chromosome encode for the basic myelin protein MBP, which is mainly significant for the myelin sheath of neurons and explains the characteristic muscle weakness of syndrome affected individuals. In type I of De-Grouchy syndrome, there is a piece loss on the short arm of chromosome 18. Type II of the syndrome is based on a piece loss on the long arm 18q22-23 of the chromosome. When ring chromosome 18 carries deletions on the long and short arms, combinations of the typical features of type I and II De Grouchy patients present.
Symptoms, complaints, and signs
De-Grouchy syndrome type I patients have low birth weight and show somatic hypotrophy with decreased muscle tone. Often, their hands are large nd bear short fingers, sometimes associated with four-finger furrowing, laterally bent phalanges, and toe syndactyly. In addition, a heart defect and intestinal location abnormalities are often present. Other symptoms may include large ears. In addition, type I often manifests as atresia or stenosis of the ear canals. Funnel chest and brain or head abnormalities such as short stature also occur. Furthermore, in addition to brachycephaly and holoprosencephaly, one-eyedness or a failure to develop the olfactory brain may be present. The cranial sutures of affected individuals often close prematurely, causing cognitive disability. Malformations of the eye muscles, ocular dysmorphia, and malformations of the orbits are characteristic of type I, as are orbital dysmorphia and small or widely spaced eyes. In addition to hypertelorism, narrow palpebral fissures, blepharophimosis, and drooping of the eyelids may be indicative of type I. Ptosis, glaucoma, or strabismus with ocular tremor is also characteristic. The patient’s mandible is often underdeveloped or displaced backward, the oral cleft is wide, and the teeth develop abnormally. The nasal cavities are often connected to the pharynx and patients suffer from retarded bone age leading to growth retardation. The spine often bends, causing a hump to develop.In addition, thyroiditis often occurs, and immunodeficiency with autoimmunological symptoms and immunoglobulin A deficiency may also develop. Patients often suffer from diabetes mellitus type 1 already in adolescence. Affected girls often do not menstruate. The leading symptom in type II of the De-Grouchy syndrome is a hypophyseal short stature. This symptom is associated with microcephaly, muscle hypotonia or narrowing of the auditory canals and ocular malformations. Type II is also characterized by dental anomalies, cognitive impairment or immunodeficiency. In 18-R syndrome, all of the symptoms described may be present.
Diagnosis
Because deletion syndrome on chromosome 18 is rare and symptoms are extremely variable, all forms of de Grouchy syndrome are difficult to diagnose. Chromosomal analysis is the diagnostic tool of choice. Differentially, the syndrome must be distinguished from the cerebro-oculo-facio-skeletal syndrome. The prognosis of patients depends on the severity and symptoms in each individual case.
Complications
Because of de Grouchy syndrome, the patient suffers from various complaints that lead to different complications. In this case, the further course depends largely on the development of the symptoms. Since there is no direct treatment for De-Grouchy syndrome, usually only the symptoms can be alleviated. In many cases, fingers and hands are affected by the syndrome. The patient complains of short fingers and large hands. These can limit everyday life and lead to bullying and teasing in children. Likewise, in most cases, a heart defect also develops. Protruding ears often lead to lowered self-esteem. The head can also be affected by the syndrome, growing too small. Often there is an immune deficiency, due to which diseases and inflammations occur more frequently. The affected person suffers from strabismus and diabetes. The quality of life decreases extremely due to the symptoms. It is usually not possible to alleviate all symptoms. First and foremost, the immune deficiency and the heart defect are treated so that the patient does not die from infections. However, life expectancy is reduced due to De Grouchy syndrome. Complaints to the muscles can be treated, with no further complications.
When should you see a doctor?
Unfortunately, causal treatment of de Grouchy syndrome is not possible. For this reason, a doctor must be consulted whenever there are various symptoms caused by de Grouchy syndrome. First and foremost, medical treatment should be sought if the patient shows immunodeficiency and thus frequently suffers from infections or inflammations. Diabetes at a young age or strabismus can also indicate De-Grouchy syndrome. Diabetes in particular requires early diagnosis and treatment to avoid further damage and complications. Early diagnosis is also useful when cognitive impairments and disabilities occur and has a very positive effect on the further course of the disease. Many of the malformations can be seen on the face and can be treated by surgical intervention. The treatment of these deformities and malformations is carried out by various specialists. However, the first diagnosis can be made by a pediatrician. Disorders of growth can also be relatively well limited by medical treatment in this case.
Treatment and therapy
Because all forms of de Grouchy syndrome involve chromosomal deletions, no causative therapy is available to treat patients. Affected individuals are treated purely symptomatically, with special attention initially paid to organic malformations. For example, if there is a heart defect, this heart defect is corrected as early as possible, usually surgically. If the abnormal skull shape restricts the brain in growth or the intracranial pressure increases, the skull bones must be opened surgically to reduce the pressure. Growth abnormalities due to pituitary hormone deficiency may be countered with hormone supplementation. Deformities of the hands can be corrected surgically. Ophthalmologic treatment is also required, most often equivalent to strabismus surgery for strabismus.Because of the muscle weakness, physiotherapeutic treatment should be given to strengthen the muscles and aim to raise muscle tone through specific exercises. Stenoses of the auditory canals can be treated surgically under certain circumstances. To support the cognitive development of patients, early intervention may be useful. From a medical point of view, not all malformations of the syndrome necessarily need to be corrected. Some of the malformations do not lead to functional impairment, but are a purely cosmetic problem. These malformations initially receive less attention in treatment planning than the functional impairments. Parents of affected children receive genetic counseling and are informed of the likelihood of recurrence.
Outlook and prognosis
De Grouchy syndrome is a hereditary disorder, which for this reason cannot be treated by symptomatic therapy. For this reason, purely symptomatic treatment is available to those affected. Self-cure does not occur with this syndrome. If the De-Grouchy syndrome is not treated, the affected persons suffer from various deformities of the body, which extremely limit their life. Furthermore, the immune system is significantly weakened, so that the affected persons suffer increasingly from inflammations and infections. In the worst case, they may even die from these, so that treatment of the syndrome is always necessary. Furthermore, the affected persons suffer from delayed development and thus from cognitive limitations and mental retardation. These limitations and delays can be resolved in many cases by intensive therapy. As a result, the affected person can usually develop. The various deformities on the body are also alleviated by surgical interventions and the quality of life is significantly improved as a result. However, a complete cure of De Grouchy syndrome is not achieved. Infections and inflammations cannot be prevented, but they can always be treated subsequently. As a rule, de Grouchy syndrome does not reduce the patient’s life expectancy.
Prevention
At best, de Grouchy syndrome can be prevented by genetic counseling during family planning.
Follow-up care
In most cases, the person affected by De Grouchy syndrome does not have any measures or options for aftercare at all, as this is a congenital disease that cannot be fully treated. If the patient wishes to have children, genetic counseling can also be performed to prevent the syndrome from recurring in the descendants. The earlier the disease is detected and treated, the better the further course of the disease usually is. The symptoms of the heart are usually solved in the young years of life by a surgical intervention. After such an operation, the affected person should in any case rest and take care of his body. Efforts or physical and stressful activities are to be refrained from in any case, in order not to stress the body unnecessarily. Physical therapy is also often necessary. Many of the exercises from such a physiotherapy can also be performed at home, which accelerates the healing process. Whether there is a reduced life expectancy of the affected person due to the De-Grouchy syndrome cannot be universally predicted.
Here’s what you can do yourself
The various forms of de Grouchy syndrome cannot yet be treated causally. Self-help measures therefore focus on supporting symptomatic therapy and making it easier for the affected person to cope with the disease. In general, in the case of chromosomal deletions, a comprehensive consultation with a specialist should take place. Especially in children, this can prevent the development of many typical fears and uncertainties associated with the disease. The parents of affected children can take advantage of genetic counseling, which provides information on how to deal with the disease and the likelihood of recurrence. Physiotherapeutic treatment can be supported by specific exercises and regular exercise. In the case of severe malformations, however, a visit to a special clinic is recommended.There, under professional guidance, the appropriate measures can be taken to reduce the movement restrictions and thus also improve the quality of life of those affected. Since complaints and restrictions in everyday life always remain despite all measures, the necessary support measures must be organized at an early stage. Any aids such as orthopedic shoes, visual aids or a wheelchair should also be organized early on in consultation with the doctor.