Bardet-Biedl syndrome, also known as Laurence-Moon-Biedl-Bardet syndrome (LMBBS), is a disorder of the ciliopathies that occurs exclusively due to heredity. The syndrome manifests as multiple malformations caused by alterations (mutations) on different gene loci or chromosomes.
What is Bardet-Biedl syndrome?
Defined by physicians Moon and Laurence and later by Bardet and Biedl, Bardet-Biedl syndrome is a disorder in which retinal dystrophy occurs as a medically significant feature in combination with other symptoms. Due to this complicated initial medical situation, the final determination of BBS disease is difficult. In 1866, this clinical picture was medically recorded for the first time. Four persons examined showed retinitis pigmentosa (retinal dystrophy, RP) in combination with paraplegia (spastic paralysis) as well as hypogenitalism (underdeveloped sexual organs) and mental retardation. In 1920, the French physician Bardet described a disease entity composed of RP (retinal dystrophy), hypogenitalism, polydactyly, and obesity. The Prague pathologist Biedl additionally noted debility (mental confusion). In 1925, researchers Weiss and Solis-Cohen summarized the known cases and named the clinical picture Laurence-Moon-Biedl-Bardet syndrome.
Causes
In subsequent years, the medical literature increasingly pointed out that the cases recorded by Laurence and Moon were a rarely occurring special form that co-occurred with BBS only in isolated cases. Recent medical research has classified Bardet-Biedl syndrome as a ciliopathy (ciliary disease). These diseases record a common malfunction of the so-called cilia (small projections, antennae), which occur on the vast majority of cells of the human organism. The ciliopathies are characterized by smooth transitions and overlaps between different cilia diseases.
Symptoms, complaints, and signs
The main feature of hereditary retinal dystrophy is a generic term describing the onset of loss of function and subsequent degeneration (destruction) of photoreceptors. It results in a progressive loss of visual function. The rapidly progressive visual disturbances usually occur very early in children, when they are between four and ten years old. They manifest themselves in different ways depending on the photoreceptors affected. As a “rod-cone form” with the characteristic disease course of retinitis pigmentosa (RP), the disease originates in the retinal periphery (outer retina) and develops into macular degeneration (destruction of sharp vision) via progressive visual field loss. In obesity, the body has a pathological accumulation of fatty tissue. In the case of BBS, morbidly increased fat accumulation on the legs, abdomen, buttocks, arms, chest, and hips occurs predominantly as truncal obesity, with the trunk, legs, and thighs being particularly affected. Polydactyly is a prominent symptom and a significant feature of Bardet-Biedl syndrome. The finding is not straightforward, as rudimentary polydactyly is surgically corrected after birth. Radiographs are able to provide further information. Polydactyly can present with different signs, for example, as a rudimentary toe or finger appendage. A toe or finger may be additionally or only partially formed. Unilateral hexadactyly on the foot and/or hand has an extra limb; bilateral hexadactyly occurs on both feet and/or hands. Fused toes or fingers (syndactyly) and shortening of single or multiple toes or fingers (brachydactyly) are also signs of BBS. Few patients have all four affected extremities. Mental developmental delay varies in severity. Only a small number of affected individuals exhibit severe mental developmental delay. A normally developed intelligence is possible. Children reach the ability to speak and walk late, also sometimes show behavioral abnormalities such as anxiety disorders. Compulsive or autistic behaviors, a low frustration threshold and unstable emotionality are other possible accompanying symptoms.What is known is preferred, changes, on the other hand, are rejected. Abnormalities of the internal and external sex organs are common. Other changes include hypospadias (the urethral opening is above or below, rather than at the front of the penis), abdominal or inguinal testes, urethral strictures, foreskin narrowing, and posterior urethral valves. In female patients, vaginal atresia (vagina is not patency), absent urethral orifices, and reduced labia minora have been reported. It is not uncommon for affected women to exhibit irregular menstrual cycles. Renal changes are common associated symptoms. Findings depend on examination of the urinary tract and kidneys by ultrasound (sonography).
Diagnosis and course of the disease
Bardet-Biedl syndrome (BBS) has six main symptoms, but they do not occur together in every case. Physicians assume a corresponding finding when at least four of the main symptoms are present. Alternatively, the disease is most likely present if the patient exhibits three major symptoms and two minor symptoms. The six major symptoms are retinal dystrophy, obesity (abnormal accumulation of adipose tissue, overweight), polydactyly (supernumerary toes and/or fingers), mental retardation (mental developmental delay), hypogenitalism (underdeveloped sex organs), and kidney disease. Secondary symptoms with a low incidence include speech delays, language deficits, cardiac malformations, ataxia (impaired coordination of movement), asthma, diabetes mellitus (diabetes), Crohn’s disease (inflammation of the large and/or small intestine), rib and vertebral dysplasias, and kyphoscoliosis (spinal curvature).
Complications
As a result of Laurence-Moon-Biedl-Bardet syndrome, affected individuals usually suffer loss of visual function. In this case, the loss does not occur suddenly but gradually. In the worst case, those affected suffer complete blindness, which usually can no longer be treated. Particularly in young people and children, blindness can lead to severe psychological complaints or even depression. Patients are significantly restricted in their everyday life and suffer from a severely reduced visual field. In many cases, Laurence Moon Biedl Bardet syndrome also leads to behavioral problems, so that children in particular can suffer from bullying or teasing. Likewise, the development of children is significantly delayed and restricted by the syndrome. Anxiety disorders may also occur. It is not uncommon for Laurence-Moon-Biedl-Bardet syndrome to cause psychological distress and depression in relatives or parents. Unfortunately, a causal treatment of Laurence-Moon-Biedl-Bardet syndrome is not possible. Some complaints can be limited. However, a completely positive course of the disease does not occur. The life expectancy of the patient is not reduced by the syndrome. In some cases, those affected are sometimes dependent on the help of other people in their daily lives.
When should you see a doctor?
Because Laurence-Moon-Biedl-Bardet syndrome is a hereditary condition, it can be diagnosed in the womb. A doctor should be consulted at the latest after birth if typical symptoms such as visual disturbances or obesity are noticed. Malformations of toes and fingers are also a clear indicator of a disease. Parents who notice such symptoms in their child should inform the pediatrician immediately. A comprehensive examination will provide information about the disease. Afterwards, therapy is usually initiated directly, which consists of various treatments by orthopedists, neurologists, ophthalmologists, internists and therapists, as well as physiotherapists. Further visits to the doctor are necessary if the treatment does not have the desired effect. Medical advice is also needed in emergency situations, such as when the child falls as a result of a deformity or suddenly suffers a seizure. If the sufferer shows signs of mental discomfort, the parents must consult a suitable therapist. Older children can contact the school psychologist together with the parents to discuss appropriate measures.
Treatment and therapy
This disorder is based on autosomal recessive inheritance, which means that both copies (allele) of a BBS gene have a change (mutation).The patient’s parents are “heterozygous” and carry one altered and one unaltered allele of the corresponding gene. The disease is not present in them. Children only become ill if both father and mother pass on the mutated allele. In additional children, the probability of recurrence is 25 percent. A causal therapy option is not yet known, since certain disease symptoms cannot yet be conclusively assigned to the various gene mutations. The symptoms and their manifestations occur differently even in affected siblings. Since the characteristic full-blown BBS is present only in rare cases, especially in young children, it is difficult to make an appropriate diagnosis. Due to the frequently present oligosymptomatics, with very few atypical and only mildly pronounced symptoms, possible other clinical pictures must be considered for differential diagnosis. Alterations in the same gene may lead to different syndromes, for example, Joubert, Bardet-Biedl, or Meckel-Gruber syndrome.
Outlook and prognosis
The prognosis in the presence of Laurence-Moon-Biedl-Bardet syndrome is rather poor overall because the multiple malformations are congenital and incurable. When four of the six leading symptoms occur, the diagnosis of Laurence-Moon-Biedl-Bardet syndrome is confirmed. In addition to the main symptoms, there are numerous secondary symptoms. These include a gradual onset of blindness. Due to the complexity of the symptoms, there is no prospect of a cure. There is only a mediocre chance of a noticeable alleviation of symptoms. The number of possible malformations and disorders in Laurence-Moon-Biedl-Bardet syndrome is so large that the hereditary disease is difficult to treat. The course of this genetic disease cannot be influenced anyway. However, the present symptoms can be partially alleviated. However, the overall poor prognosis does not reduce the life expectancy of affected individuals. In advanced age and after blindness, affected individuals may be permanently dependent on assistance or care. Through interdisciplinary medical efforts, many affected individuals with Laurence Moon-Biedl-Bardet syndrome can experience a somewhat milder course of the disease. The increasing visual problems represent a problematic part of the disease that is difficult to treat. Increasing visual impairments already occur in affected infants. They worsen over time. However, the visual problems do not have to lead to blindness in all those affected. The psychological sequelae of Laurence-Moon-Biedl-Bardet syndrome can usually be treated well.
Prevention
Prevention in the sense of preventing this disorder is not possible. Regular monitoring of the symptoms and accompanying symptoms that occur is important. Repeated checks of blood pressure and kidney function, nutritional counseling, physical and occupational therapy, and speech therapy are possible therapeutic approaches.
Follow-up care
In most cases, there are no special aftercare options available to the affected person with Laurence-Moon-Biedl-Bardet syndrome, so a physician should be contacted and consulted very early in the course of this disease. Self-cure usually cannot occur, so treatment by a physician is always necessary. Since Laurence-Moon-Biedl-Bardet syndrome is a hereditary disease, the affected person should have a genetic examination and counseling if he or she wishes to have children, so that Laurence-Moon-Biedl-Bardet syndrome is not passed on to the offspring. In many cases, those affected by this disease rely on surgical interventions to alleviate the malformations and deformities. In this case, the affected person should in any case rest and take care of his body after the operation. In any case, the patient should refrain from exertion or other physical and stressful activities in order not to put unnecessary strain on the body. Since Laurence Moon Biedl Bardet syndrome can also lead to conspicuous behavior, parents should support and encourage the child’s development. In this context, loving and intensive conversations with the child are also necessary to prevent psychological upsets or depression.
This is what you can do yourself
Laurence-Moon-Biedl-Bardet syndrome presents with a variety of symptoms, with patients often suffering most severely from impaired visual function.Even in children, the usual ability to see begins to decline, so that it is the parents who present the child to a doctor and thus accelerate the diagnosis. In this way, the disease can be treated quickly, although the treatment options so far are only symptomatic in nature. The visual disturbances become increasingly severe in the children with the disease, significantly impairing their normal daily lives and reducing their quality of life. This is because the vision problems cause numerous difficulties for the patient when attending school, during leisure time and with regard to his or her physical integrity. The risk of accidents also increases significantly, for example in road traffic. For this reason, parents accompany their sick children if possible or hire caregivers so that the patient is not left on his or her own. In some cases, the disease progresses to blindness. Since such a development is already apparent beforehand, the patients prepare themselves for it. The parents redesign the living space so that it does not contain any sources of danger for the visually impaired person. In addition, the blind affected person learns how to use a long cane so that independent locomotion outside of their own home is possible.