Louis Bar Syndrome: Causes, Symptoms & Treatment

Louis Bar syndrome is a hereditary multisystem disorder. Almost all organs are affected by the disorders. The life expectancy of affected individuals is significantly reduced.

What is Louis Bar syndrome?

Louis Bar syndrome is a hereditary systemic disorder. It involves neurological deficits, frequent infections, and malignant degeneration of various body cells. The disease is very rare and occurs in one out of 40000 newborns. As an inherited disease, it belongs to the so-called phakomatoses. Phakomatoses are a group of diseases with skin malformations and nerve damage. It is not a uniform group of diseases, but a collective term. Furthermore, the disease is also counted among the chromosome break syndromes, because in its course multiple chromosome breaks occur. In neurological practice, Louis-Bar syndrome is classified in the group of heteroataxias (inherited ataxias). Life expectancy is significantly limited. In most cases, the syndrome is fatal in the third decade of life. However, individual patients have also reached a much older age. The disease was first described by the Belgian physician Denise Louis-Bar in 1941. For this reason, the syndrome was named after Denise Louis-Bar.

Causes

The cause of Louis-Bar syndrome is due to a defect in the ATM gene on chromosome 11. There have been 400 different mutations detected on this gene. It encodes a large nuclear protein that is found in all cells. The protein is called serine protein kinase ATM and is responsible for detecting DNA damage, especially that related to chromosome breaks. ATM is responsible for producing DNA repair proteins by sending out appropriate signals. It can also induce cell death (apoptosis) in the event of major DNA damage. It also regulates other genes involved in cell division. Many neurological and immunological symptoms are due to a dysregulated stress response. The syndrome is inherited in an autosomal recessive manner. Heterozygous carriers are healthy but often have increased susceptibility to tumor formation. Overall, the pathogenesis of the individual disease manifestations is not fully understood.

Symptoms, complaints, and signs

Louis Bar syndrome manifests itself in many different symptoms. After an initially undisturbed development, the first motor disorders often appear in early infancy in the form of ataxias (gait unsteadiness) and balance disorders. Later, abnormal movements and muscle twitching are added. Furthermore, there is a bent posture and tremor (shaking). Eye movements are also disturbed. Head and eye movements are no longer coordinated. Speech deteriorates, with speech sounding increasingly slurred. From the third to fifth year of life, telangiectasias appear. These are dilations of the small arteries in the face and on the conjunctiva of the eyes and ears. The facial skin tightens, the hair turns gray and other premature signs of aging appear. In addition, foot deformities or spinal curvatures develop. A large part of the symptoms is related to immune disorders. Frequent infections of the respiratory tract and constant pneumonia occur. It was found that mainly the immunoglobulins IgA and IgG2, but sometimes also IgG4 and IgE, are absent. With an initially normal mental development, an increasing mental decline takes place from the age of ten. During the second decade of life, motor problems worsen to such an extent that adolescents are dependent on a wheelchair. During puberty, sexual development is delayed with development of short stature and hypogonadism. The risk of developing malignant degenerations in the form of lymphomas, leukemias and other carcinomas is between 60 to 300 times more frequent compared to the normal population.

Diagnosis and disease progression

A diagnosis of Louis Bar syndrome is easily made after the characteristic telangiectasias appear on the conjunctiva of the eyes, in addition to the motor abnormalities already present. The diagnosis is further confirmed by the detection of an increased concentration of the alpha-fetoprotein AFP. In the cell cultures, frequent chromosome breaks are noticeable, especially in chromosomes 7 and 14.Magnetic resonance imaging reveals atrophy of the cerebellum.

Complications

Louis Bar syndrome results in a very severe reduction in life expectancy. In this case, especially the parents or the relatives also suffer from psychological complaints and also depression and therefore need psychological treatment. The patients themselves suffer from muscle twitching and balance disorders. Furthermore, there is also a limited ability to speak and thus severe restrictions in everyday life. The respiratory tract is also significantly affected by Louis Bar Syndrome, often leading to inflammation and other disorders of the immune system. Furthermore, affected individuals are affected by short stature and usually also suffer from various cancers. Whether Louis Bar Syndrome also causes mental retardation cannot generally be predicted. Unfortunately, it is not possible to treat Louis-Bar syndrome causally. For this reason, treatment is exclusively symptomatic and aims at increasing the patient’s life expectancy. For this purpose, various interventions and therapies are necessary, which, however, do not lead to success in every case. In most cases, life expectancy is limited by Louis Bar syndrome to about thirty years.

When should you see a doctor?

If growing children show a delay in development when compared directly to their peers, observations should be discussed with a physician. If motor peculiarities become apparent, if there is unsteadiness of gait or difficulty in locomotion, a visit to the doctor is advisable. Disturbances of the balance, a bent posture, problems of the spine or trembling of the limbs should be medically examined and treated. In case of decreased speech, coordination problems of head and eye movements, and behavioral abnormalities, the affected person needs medical help. Problems with respiratory activity, infections, a general feeling of illness and internal weakness should be clarified. If there are abnormalities in the appearance of the skin, unusually tight facial skin or dilatation of the arteries in the face, a doctor should be consulted. Malpositions of the feet are further signs of an irregularity. They should be medically examined so that the cause can be determined and treatment can be initiated. Without timely care, the affected person risks permanent postural damage and further complications that can lead to lifelong consequences and impairments. A visit to the doctor is necessary if the hair on the head turns gray prematurely, if an early decline in mental abilities emerges, or if repeated inflammations of the respiratory tract develop. If there is an occurrence of repeated pneumonia, the observations should be discussed with a doctor.

Treatment and therapy

Louis Bar syndrome cannot be treated causally because it is a hereditary condition. Only symptomatic therapies are possible. This requires ongoing antibiotic treatment for the frequent infections. The administration of vitamins has been shown to be helpful. Furthermore, it is also important to carry out the usual vaccinations. However, it is important not to use live vaccines. Since there is increased mutability, the use of radiation therapy should be strictly avoided. X-rays should also not be used in diagnostics. Promotional measures such as occupational therapy and speech therapy should be initiated at an early stage. Physiotherapeutic measures are also necessary. Orthopedic aids can improve the possibilities of movement. Furthermore, constant monitoring must take place with regard to the occurrence of malignant tumors. Radiation treatment of leukemias and lymphomas is not possible due to their particular sensitivity to radiation. The prognosis of the disease is unfavorable, but can be improved by intensive medical care. As a rule, Louis Bar syndrome is fatal in the third decade of life. However, in isolated cases, patients have reached a much older age.

Outlook and prognosis

Louis Bar syndrome has an unfavorable prognosis. The affected individual has a genetic disorder. There is also an increased susceptibility to tumor formation. Legal requirements prohibit intervention and alteration of human genetics.For this reason, the cause of the syndrome cannot be eliminated. The patient is bound to regular check-ups for the rest of his life so that abnormalities and irregularities can be detected as early as possible. The complaints as well as the fact of increased cancer susceptibility represent a strong emotional burden for the patient. In addition to the development of various cancers, a psychological disorder may also develop. Overall, the life expectancy for sufferers of Louis Bar syndrome is considerably reduced. In most cases, those affected reach an age of about thirty years. The detailed development depends on the individual severity of the individual symptoms. An improved course is recognizable in patients who have a healthy lifestyle and pay attention to their mental stability within the scope of their possibilities. In addition, practices learned in therapies can be applied independently to promote quality of life. This supports mobility and makes it easier to cope with everyday life. The prospect of a reduced life expectancy is a challenge for the person affected as well as their relatives. Dealing with the disease is therefore not irrelevant to further development.

Prevention

Because Louis Bar syndrome is a hereditary disorder, there can be no recommendations for its prevention. However, if there is a family history of this condition, genetic counseling should be sought. A mutation at the ATM gene can be detected during prenatal diagnosis.

Follow-up

Affected individuals with Louis Bar syndrome suffer from a number of different symptoms and complications, all of which can usually have a very negative impact on the affected individual’s quality of life. As a result, follow-up care focuses primarily on managing the balance disorders. As a result, the affected person suffers from restrictions in movement and is usually dependent on the help of the family in everyday life. In general, the disease cannot be cured, so aftercare is primarily aimed at containing the symptoms and complications that arise and ensuring a certain level of quality of life in everyday life. Depending on the severity, the disease can take a heavy toll on those affected, which is why it is sometimes advisable to seek professional help from a psychotherapist. Sharing knowledge with other sufferers can also boost self-esteem in dealing with Louis Bar syndrome.

Here’s what you can do yourself

Louis Bar syndrome is a serious condition that often takes a fatal course. Because caring for a sick child involves stress and anxiety, parents of affected children usually need therapeutic support. Many parents also participate in self-help groups or obtain further information about the disease when visiting a specialist clinic for hereditary diseases. The affected child usually has to be treated in hospital. Any accompanying measures are limited to making the hospital stay as pleasant as possible for the child. This is achieved by both the relatives and the doctors being available to answer questions or solve problems. If the outcome is positive, the aim is to correct any deformities that have arisen by starting occupational therapy at an early stage. At home, these measures can be supported by individual training. Parents should talk to the responsible physiotherapist or a sports physician for this purpose. If logopedic measures are initiated, parents should primarily pay attention to unusual symptoms. Close medical monitoring ensures that any malignant tumors can be detected and treated immediately. Affected children often need psychological help later in life, as Louis Bar syndrome significantly reduces life expectancy and quality.