Dubowitz syndrome is a rare inherited disorder that is associated with symptoms such as short stature and facial deformities. The condition was named after British pediatric neurologist Victor Dubowitz.
What is Dubowitz syndrome?
Victor Dubowitz first described Dubowitz syndrome in 1965. The disorder is an autosomal recessive [[hereditary diseases|hereditary disease[[ that is rather rare. Currently, only 150 cases are known worldwide. Thus, Dubowitz syndrome belongs to the so-called orphan diseases. Orphan diseases are diseases that occur so rarely that they appear in a normal medical practice at most once a year. Dubowitz syndrome is associated with many different symptoms. According to the observations of Masato Sukahara and John M. Opitz, however, not all symptoms have to occur. The scientists found that facial malformations are the most important diagnostic sign of Dubowitz syndrome. These occurred in 112 of 141 cases of the disease. Strikingly, despite the marked microcephaly, severe intellectual disability is rare in many sufferers. Most patients with Dubowitz syndrome develop normally cognitively.
Causes
The cause of Dubowitz syndrome is still unclear. However, the disorder is thought to be inherited via an autosomal recessive mode of inheritance. In autosomal recessive inheritance, the defective allele is located on both homologous autosomes. The disease is thus inherited independently of sex. In autosomal recessive inheritance, both parents are usually healthy and heterozygous. Heterozygous means that the genetic material of a cell has two different gene copies on both autosomes or chromosomes. The child can only develop the disease if both parents are carriers of the defective gene. Carriers of the defective allele are called conductors. The statistical probability that the child of two conductors will get the disease is 25 percent. If one parent has the disease and the other parent is a trait carrier, the risk increases to 50 percent. How the symptoms of Dubowitz syndrome develop is also unknown.
Symptoms, complaints, and signs
The condition can manifest as a variety of symptoms. A leading symptom is physical retardation. Affected individuals often suffer from short stature. Short stature refers to body length growth that does not conform to the norm. In addition to short stature, microcephaly often occurs. In microcephaly, the head has a small size. It is three standard deviations smaller than the mean for people who are the same age and sex. Microcephalies are actually associated more often with intellectual disabilities. In Dubowitz syndrome, however, the disabilities are only mild to moderate. Half of all patients have no cognitive impairments and develop according to the rules. On the other hand, some patients suffer from eczema associated with itching and reddening of the skin. Hyperactivity is also typical of Dubowitz syndrome. This is characterized by abnormal mental overexcitability. Affected individuals suffer from motor restlessness and have difficulty concentrating. Most patients with Dubowitz syndrome have facial malformations, so-called craniofacial dysmorphia. These include, for example, a reduced palpebral fissure (blepharophimosis), a missing nasal saddle, excessive interpupillary distance, or low ears. Similarly, malformations of the eyes and malformations of the teeth can occur. Symptoms such as heartburn or constipation may develop due to malformations of the digestive tract. In some patients, congenital constipation develops due to anal stenosis. Furthermore, malformations of the central nervous system may occur in Dubowitz syndrome. Aplasia of the corpus callosum is typical. This structure is a fiber connection that runs between the two halves of the brain. The corpus callosum ensures that information can be exchanged between the two cerebral hemispheres. In some cases, hypoplasia of the pituitary gland also occurs. As a result, hormone production in the pituitary gland may be impaired. There are various malformations of the musculoskeletal system that can be caused by Dubowitz syndrome. On the fingers, nail hypoplasia or shortening of individual fingers may be seen.Nail aplasia or nail hypoplasia are also possible on the feet. Furthermore, adhesions of adjacent fingers or toes occur. Patients with Dubowitz syndrome often suffer from dysplasia of the hip. In individual cases, a so-called coxa valga has also been observed. In this axial malposition of the femoral neck, a steep position is present. The joints of patients with Dubowitz syndrome are often hypermobile. Some affected children are born with spina bifida or scoliosis. Spina bifida is an embryonic closure disorder of the back in the spinal region. It is popularly known as open back. In scoliosis, the spine deviates laterally from the longitudinal axis. Patients with Dubowitz syndrome are more likely to suffer from infections such as middle ear infections, pneumonia, sinusitis, whooping cough, or brain infections. Neurological symptoms such as migraines, convulsions, bladder and anal paralysis, or impaired reflexes may also occur.
Diagnosis
The diagnosis is made after a detailed clinical examination. Facial malformations and short stature provide clues to the disease. There is as yet no specific molecular genetic or cytogenetic diagnostic test for Dubowitz syndrome.
Complications
Because of Dubowitz syndrome, patients are affected by a variety of malformations that can develop throughout the body. In most cases, there is also short stature. In addition to the reduced height, the patient’s head is also much smaller than usual. Often there are also complaints on the skin. Redness and itching may develop. Intelligence and cognitive abilities are not limited, so the patient can develop in an ordinary way. In case of malformations of the stomach or the digestive tract, heartburn may occur. It is also not uncommon for adhesions of fingers and toes to occur. Likewise, infections occur more often, which can affect the lungs or nose. In severe cases, inflammations of the brain also occur. The malformations can cause insecurity and self-doubt in those affected, resulting in psychological discomfort. Because of the malformations, children in particular are teased and bullied. A causal treatment of Dubowitz syndrome is not possible, which is why only the symptoms are alleviated. The affected person must undergo various examinations to diagnose tumors, if necessary, and to remove them. Usually, there is no decreased life expectancy.
When should you see a doctor?
Dubowitz syndrome is usually diagnosed immediately after birth. The doctor can identify the condition by the small stature and typical facial deformities, and prompt treatment can be initiated. If one parent has the disease, a medical examination should be performed before birth. Then, together with the doctor, a decision can be made on how to proceed. If the affected person suffers from eczema, itching and redness of the skin, a dermatologist can be consulted. A therapist can help with the hyperactivity that often occurs. Parents who notice behavioral problems in their child should also talk to a specialist in the disease. He or she can provide further tips and assistance and, if necessary, refer the affected person to a special clinic. In case of severe complications such as lung, brain or sinus infections, the emergency physician should be called. Since Dubowitz syndrome can take on many forms, comprehensive cooperation with a team of physicians is necessary. They should be informed of all complaints and abnormalities so that said complications do not arise in the first place.
Treatment and therapy
Dubowitz syndrome cannot be treated causally. Possible malformations may eventually be corrected surgically. Growth, overall health, language development, dental status, and cognitive development should be evaluated by a physician at regular intervals. Because malignant neoplasms are common as a result of immunodeficiencies in the course of the disease, regular targeted screening for tumors is necessary.
Outlook and prognosis
In general, Dubowitz syndrome cannot be treated causally because it is a genetic disorder.Affected individuals are therefore dependent on purely symptomatic treatment, which can limit the deformities and thereby increase the quality of life. Self-healing does not occur with this syndrome. If no treatment of Dubowitz syndrome takes place, those affected often suffer from severe itching or heartburn. This can also lead to hyperactivity or developmental disorders in children, which also makes everyday life in adulthood much more difficult. Furthermore, the patients suffer increasingly from various inflammations and can die from these in the worst case if they are not treated. Paralysis and limitations of reflexes are also common in this syndrome. The treatment itself can only limit the symptoms, with a high emphasis on the child’s ordinary development. Furthermore, those affected depend on regular examinations in order to detect and treat tumors at an early stage. In most cases, the life expectancy of the patient is reduced by the syndrome. The syndrome can lead to severe psychological upset or depression not only in the affected person, but also in the relatives and parents.
Prevention
Dubowitz syndrome cannot be prevented.
Follow-up care
In most cases of Dubowitz syndrome, very few aftercare measures are available to the affected person. First and foremost, the disease should be detected early to prevent further worsening of symptoms that can limit the life of the affected person. Since this is a genetic disease, it cannot be completely cured, so that only purely symptomatic treatment is possible. If the patient should wish to have children later in life, a genetic examination with subsequent counseling can also be performed in order to possibly prevent the inheritance of Dubowitz syndrome to the descendants. In most cases, the affected children are dependent on intensive and special support due to the syndrome, so that there are no complaints during development. Parents can significantly promote this development with various exercises. Since the syndrome can promote the occurrence of tumors, regular examinations by a doctor are very useful. In many cases, patients also rely on support from friends and family in their daily lives.
Here’s what you can do yourself
Dubowitz syndrome is a very rare hereditary disease for which short stature and malformations of the face in particular are characteristic. The disease cannot be treated causally. The patient himself can only take measures to alleviate the symptoms. The short stature is often accompanied by a restriction of motor skills. Affected persons should therefore start physiotherapy as early as possible, aimed at improving their mobility. Insofar as it becomes apparent that a child will later be dependent on walking aids, parents should encourage him or her to learn how to use them at an early age. Children suffering from Dubowitz syndrome usually show no or only mild forms of mental retardation. However, they are very often hyperactive. In addition, their development is inhibited by their short stature. Parents should therefore consult experts at an early stage to ensure optimal educational and psychological support for their child. A suitable school should also be sought in good time. The children’s cognitive abilities usually allow them to attend regular classes. However, many schools are unable to provide adequate care for students with significant physical retardation. This is especially true because the affected children are often teased or even bullied by their peers due to their facial deformities and the teachers usually do not have the necessary socio-educational training to deal with such situations.
