Mowat-Wilson syndrome

The Mowat-Wilson syndrome is a rare, genetic developmental disorder with a wide range of symptoms. In addition to facial, intestinal and genital anomalies, heart defects and brain development disorders occur as part of the genetic defect. The so far incurable disease can only be treated symptomatically.

What is Mowat-Wilson Syndrome?

The Mowat-Wilson syndrome is a rather young clinical picture. The clinically diverse phenomenon was first described by Mowat and Wilson in 1998. In addition to developmental disorders, microcephaly and the symptom complex of Hirschsprung's disease characterize the clinical picture. A genetic defect is considered to be the cause of the disease.

Overall, the symptoms are extremely diverse. The rare disease has so far been little researched. As a result, few therapy options are available so far. There is no definitive prevalence because the disorder could rarely or not at all be diagnosed well into the 21st century. There are currently around 200 documented patients with the syndrome.

causes

A gene mutation causes Mowat-Wilson syndrome. According to recent research, the ZFHX1B gene is the disease-causing gene. The causal genetic defect is said to be in chromosome region 2q22. The affected gene is around 70 kb in size and consists of a total of ten exons of 1214 amino acids. This gene encodes the protein SIP1, which is active as a transcription modulator and is involved in embryogenesis.

The embryogenesis of those affected is therefore disturbed. The disease-causing anomalies of the gene can correspond to a complete deletion, a repositioning or a sequential anomaly. The genetic defect is passed on in the autosomal dominant inheritance. A defective allele on the two homologous chromosomes is sufficient to pass on the hereditary disease.

Symptoms, ailments & signs

The symptoms of Mowat-Wilson syndrome correspond to a complex developmental disorder and are clinically diverse. The main symptoms include cerebrally triggered seizures and microcephaly. Such a microcephaly occurs as a result of the premature hardening of all cranial sutures and constricts the brain during the growth phase. Because of this, patients experience mental retardation. In addition, there are often abnormalities of the face that often give the patient an eagle-like profile.

These anomalies may include, for example, large, deep-set eyes, horizontally-pointing eyebrows, auricle abnormalities, ingrown earlobes, and a prominently protruding chin. In 90 percent of the cases, those affected suffer from epilepsy. Mental development is severely delayed and linguistic development is often completely absent. The patient's motor development is also slowed down.

With normal birth measurements, secondary short stature often occurs. There may be malformations of the urethra. Congenital heart defects or malformations of the genitals are also conceivable. In addition, neuronal abnormalities of the intestinal wall plexus occur, as they are characteristic of Hirschsprung's disease.

Diagnosis & course of disease

The diagnosis of Mowat-Wilson syndrome cannot be made on the basis of mere examinations, but requires analysis of the genetic material. The laboratory amplifies exons two to ten of the ZFHX1B gene from the patient's genomic DNA. This amplification takes place using PCR. Analysis of this material and the intron-exon splice sites takes place via DNA sequencing.

Each exon of the ZFHX1B gene is examined for deletion and duplication via multiplex ligation-dependent probe amplification. This elaborate procedure takes around three weeks and, unlike the mere examination of the patient, can enable an unequivocal diagnosis to be made. In most cases, in addition to the person's DNA, that of his or her parents is also sequenced and analyzed.

The course of the disease depends heavily on the form of the genetic abnormality and the extent of the deletion or repositioning of chromosome parts. Definitive prognoses can hardly be made because of the so far little documented cases of illness. However, an early diagnosis and the subsequent therapy will probably have a positive influence on the prognosis.

Complications

The Mowat-Wilson syndrome causes serious complaints and complications in the patient, which significantly reduce life expectancy and quality of life. As a rule, the patient's everyday life is also significantly restricted and those affected depend on the help of other people in their everyday life.

Furthermore, there is mental retardation in which relatives and parents often suffer from psychological complaints or depression. In most cases, those affected also suffer from cramps and decreased resilience. Furthermore, various deformations of the face also occur and epilepsy occurs.

Linguistic development is also significantly delayed, so that in adulthood there are considerable difficulties communicating with the patient. A heart defect and short stature also occur. The heart defect can lead to spontaneous cardiac death, so that the life expectancy of the person affected is limited by Mowat-Wilson syndrome.

There is no cure for Mowat-Wilson syndrome. However, the various complaints can be restricted and treated so that the person concerned has a bearable everyday life. There are no complications, but positive treatment is not always possible.

When should you go to the doctor?

Although Mowat-Wilson syndrome cannot be cured with the current legal and medical options, treatment of the symptoms that occurs can provide significant relief. Normally, the earlier a diagnosis can be made, the better the patient's therapeutic options. Consultation with a doctor is necessary if a developmental disorder occurs in the growing child.

If there are individual abnormalities in direct comparison with those of the same age, a doctor is required. The observations should be discussed with him so that an assessment of the state of health is possible. A doctor should be presented with a learning disability, memory impairment, speech delay or peculiarities of movement sequences. If you experience cramps, pain or abnormal posture, you should see a doctor. Facial malformations or abnormalities indicate a condition that requires treatment.

A visual flaw or abnormalities in facial features should be clarified by a doctor. Slowed thought processes or movements are signs of a disorder and should be investigated. If there are disturbances in the heart rhythm, problems with the excretions or irregularities in the ability to react or perceive, a doctor should be consulted. Behavioral disorders, vegetative disorders or peculiarities of the skin's appearance must be examined by a doctor.

Treatment & Therapy

The Mowat-Wilson syndrome is so far incurable. Symptomatic treatment options are also limited. Medicinal therapies are usually used against seizures. Antiepileptic drugs show the greatest effectiveness in this context. Some of the symptomatic malformations can be corrected surgically. In particular, the symptoms of Hirschsprung's disease should be corrected as early as possible, as otherwise sepsis or peritonitis could set in.

Symptomatic therapy for Mowat-Wilson syndrome is primarily intended to improve the quality of life of those affected. With this aim, mental and motor retardation can also be counteracted. Speech therapy therapies can under certain circumstances help with language development, which in Mowat-Wilson syndrome often fails completely without supportive therapeutic measures. Physiotherapeutic and occupational therapy treatments can counteract the delayed development of motor skills.

Mowat-Wilson syndrome is often an almost unimaginable psychological burden for the parents of an affected person. For this reason, the parents of the patients are often supported by psychotherapists. Medical research is currently concerned with gene therapy approaches that should heal gene defects in the future. In this way, the defective ZFHX1B gene in those affected can soon be replaced, which may make the disease curable.

Outlook & forecast

Mowat-Wilson syndrome can be treated well these days. Life expectancy and quality of life are based on the type and severity of the congenital malformations. With mild abnormalities that do not affect the heart, those affected can live into adulthood.

Seriously ill patients usually die during childhood or adolescence as a result of the disease. Typical causes of death are myocardial infarction or the characteristic HSCR diseases. Cerebral seizures often result in death during the child's first years of life. The rare syndrome can be treated symptomatically, which means that patients can lead a symptom-free life, at least temporarily.

In the long term, however, Mowat-Wilson syndrome does not offer a positive prognosis, as the various malformations and anomalies result in a progressive deterioration in the state of health and ultimately lead to death. The prognosis for life expectancy and the course of the disease is usually made by the responsible specialist. Most of the time it is a neurologist or a specialist in genetic diseases. Depending on the symptoms, the diagnosis of the disease can be difficult, which is why Mowat-Wilson syndrome is often not diagnosed before the disease is well advanced.

prevention

Since Mowat-Wilson syndrome is a complex developmental disorder with a genetic cause, the phenomenon can hardly be prevented. Couples involved in family planning may, however, have their DNA sequenced in order to assess their personal risk of passing on genetic defects.

Aftercare

In most cases, those affected with Mowat-Wilson syndrome have no or only a few follow-up measures available, as this is a genetic disease. Therefore, those affected should ideally consult a doctor at an early stage so that there are no further complaints or complications that could have a negative impact on the life expectancy and quality of life of the person concerned.

As a rule, self-healing cannot occur, so that a doctor should be consulted at the first signs and symptoms of the disease. If you want to have children, genetic testing and counseling can be useful to prevent the syndrome from recurring in your descendants. As a rule, those affected with Mowat-Wilson syndrome are dependent on the intake of various medications.

These should always be taken in good time and in the correct dosage to alleviate the symptoms. In the case of children, the parents in particular should control the intake. Physiotherapy measures are also necessary in many cases, although some of the exercises can also be performed in your own home. It cannot be universally predicted whether the Mowat-Wilson syndrome will lead to a reduced life expectancy for the person affected.

You can do that yourself

Since there are unfortunately no cures for Mowat-Wilson syndrome, the main priority is currently to improve the child's quality of life.

In many cases, speech therapy started early can counteract the delayed linguistic development and ensure significant success in language development. In addition, intensive physiotherapeutic and occupational therapy measures ensure better motor and mental development. In addition to the measures prescribed by the doctor, it is also advisable to deal with the topic yourself and to continue the therapy at home.

Caring for a disabled child is an enormous burden, especially for the parents, but also for any siblings that may be present, which can affect family life and ultimately the quality of care. It is therefore extremely important that in such cases the parents seek psychotherapy in good time that gives them more strength in the long term by learning methods for relaxation and conflict management.

It should also be borne in mind that those affected are entitled to preventive care of up to six weeks each year, for which the care insurance pays the costs. There are already facilities that provide intensive care during the day while relatives can relax on excursions. This can be of great help, especially with siblings.