Laurence-Moon-Bardet-Biedl syndrome is an autosomal recessive neuroendocrine disease characterized by obesity, dystrophic lesions of the retina, intellectual disorders. Pathology is also manifested by various deformities of the skeleton, congenital malformations of internal organs, neurological complications. To diagnose the disease, neuroimaging, fundus examination, and a comprehensive laboratory examination are required. Supportive therapy includes medications (nootropics, hormones), diet, speech therapy and defectological correction.
Q87.8 Other specified syndromes of congenital anomalies, not classified elsewhere
The first information about pathology appeared in 1866, when the English ophthalmologist D. Laurence and the American ophthalmologist R. Moon described a family case of obesity, mental retardation and tetraparesis that subsequently developed. In the 20s of the twentieth century, the French physician J. Bardet and the Hungarian specialist A. Bidl announced similar clinical observations, which in 1925 were combined into one disease — Laurence-Moon-Bardet-Biedl syndrome. In Europe and the USA, the disease occurs with a frequency of 1 case per 140-160 thousand people, and in Asian and African countries — 2-3 times more often.
To date, more than 15 variants of gene defects have been described, in which the Laurence-Moon-Bardet-Biedl syndrome occurs. 45% of cases are associated with a mutation at the BBS1 (11q13) locus, BBS2 (16q22), BBS3 (3p13), BBS4 (15q21) are also common. The inheritance of the disease occurs according to an autosomal recessive type, but a clear family character can be traced only in 40% of patients. Pathology has variable penetrance.
According to the mechanism of development, the syndrome belongs to the category of ciliopathies, which are characterized by a violation of the structure and functioning of the cilia. Normally, these formations are located on the surface of cells of various tissues, and they are divided into primary (stationary) and secondary (mobile). For the pathology of Laurence-Moon-Bardet-Biedl, the defeat of the primary cilia, consisting of 9 pairs of peripheral microtubules, one pair of central microtubules, is typical.
Despite their immobility, cilia are involved in many physiological processes in the cell: they help in the transport of cellular signals, affect the peculiarities of the course of biochemical reactions, contribute to the correct orientation of the division plane. Under physiological conditions, they are contained in photoreceptors, kinocilia, osteocytes, and other cells of internal organs, therefore, patients with Laurence-Moon-Bardet-Biedl syndrome have polymorphism of symptoms.
The first clinical manifestations of the syndrome occur already in early childhood, however, due to the variety of symptoms and the absence of pathognomonic signs, they are not always diagnosed in a timely manner. The most typical target organs are: eyes, tubular bones, organs of the endocrine system, and the brain. Some scientists suggest separating Laurence-Moon-Bardet-Biedl syndromes separately, but this theory has not yet received proper support.
The Laurence-Moon-Bardet-Biedl syndrome is characterized by overweight, 72-92% of patients are obese according to the central type — the maximum amount of fat deposits is concentrated in the abdomen. As a result of metabolic disorders, half of the patients develop type 2 diabetes mellitus. Pronounced hypogonadism (underdevelopment of the genitals) is detected in 74-85% of men, 45-53% of women.
Specific signs of the disease are malformations of the skeleton by the type of short—fingered (brachydactyly), occurring in 42-100% of patients, an increase in the number of fingers or toes (polydactyly) – 63-81%, finger fusion (syndactyly) — 8-95%. The lesion of the visual apparatus is mainly represented by retinitis pigmentosa (in 93% of patients), leading to progressive deterioration of vision. Astigmatism, strabismus, and cataracts are less often diagnosed.
Another typical group of symptoms in Laurence-Moon-Bardet-Biedl disease is neuropsychiatric disorders. In early childhood, 90% of patients have delayed speech development of varying severity, and subsequently more than 80% of patients have speech defects. Mental retardation occurs in 75-90% of cases. Neurological disorders are represented by disorders of coordination of movements, a decrease in the function of the olfactory nerve.
The course of the Laurence-Moon-Bardet-Biedl syndrome is often complicated by a variety of somatic diseases. In 68% of cases, renal insufficiency develops due to hydronephrosis, polycystic or other kidney abnormalities. More than half of the patients face dental problems, extensive carious lesions of the teeth. More rare complications of hereditary disease include liver fibrosis, congenital heart defects.
Pathology is characterized by rapid weight gain, so obesity is observed starting from preschool age, and quickly reaches 3-4 degrees. Against this background, severe metabolic disorders occur, the risk of endocrine diseases and cardiovascular diseases increases significantly – 50% of patients over 34 years of age have arterial hypertension. With severe damage to the cerebral structures, convulsive seizures, spastic paraplegia or tetraplegia, extrapyramidal disorders are possible.
With a detailed clinical picture, diagnosis is not difficult, the diagnosis of Laurence-Moon-Bardet-Biedl syndrome is possible after a clinical examination by a pediatrician or a geneticist. However, incomplete forms of the disease are often missed by pediatric doctors, which is why supportive therapy is prescribed late. The following methods are used to confirm the diagnosis:
- Radiography of the skeleton. The study is performed for a detailed study of the structure of the fingers and feet, assessment of the degree of bone deformities, preparation for surgical correction of polydactyly and syndactyly.
- Ophthalmoscopy. Over the entire surface of the fundus, pigment accumulations are detected in combination with narrowing of the retinal arteries, signs of degeneration in the macular zone. This pattern indicates the occurrence of retinitis pigmentosa.
- Neuroimaging. According to the results of CT or MRI of the brain, most patients have agenesis of the corpus callosum, anomalies of the structures of the posterior cranial fossa. In patients with convulsive syndrome, the diagnosis is supplemented by an EEG.
- Kidney examination. As a screening diagnostic method, ultrasound of the kidneys is used, according to which congenital structural anomalies of the organ are detected. The functional activity of the kidneys is assessed using renoscintigraphy.
- Laboratory methods. Blood test, lipidogram, fasting glucose analysis and glucose tolerance test are recommended for patients. The levels of insulin, C-peptide, and the content of sex hormones are also being investigated.
There is no specific treatment for the disease. A multidisciplinary team, which consists of an endocrinologist, a neurologist, a neuropsychologist, correctional educators and other specialists, is engaged in providing medical care. Taking into account the leading clinical symptoms in a particular patient , the following areas of therapy are used:
- Diet therapy. To control body weight, prevent diabetes mellitus and hyperlipidemia, a diet with a reduced amount of simple carbohydrates, saturated fats is selected. Patients are recommended a balanced caloric diet with an increased content of vitamins, trace elements.
- Hormone therapy. Gonadotropin replacement therapy is used to correct hypogonadism, possible restoration of reproductive function. In case of metabolic disorders, insulin administration may be required.
- Eye protection from UV light. To prevent retinitis pigmentosa, patients are shown wearing high-quality sunglasses, in adolescence, the option of contact lenses with UV filters is considered.
- Nootropic therapy. Specific drugs are prescribed to stimulate cerebral circulation, improve metabolic processes in the nervous tissue. Treatment allows you to correct intellectual disabilities, delay in the development of speech skills.
- Neuropsychological rehabilitation. Patients with reduced intelligence need the help of speech pathologists, the selection of special training programs. Speech therapy correction is necessary to eliminate speech disorders.
- Surgical treatment. The help of surgeons is necessary to eliminate congenital anomalies of the fingers and toes to improve their functionality, achieve the maximum possible cosmetic result.
Given the likely complications, patients with Laurence-Moon-Bardet-Biedl syndrome require lifelong follow-up by an ophthalmologist, cardiologist, nephrologist. In order to monitor the condition of internal organs, laboratory and instrumental testing is regularly carried out, and appropriate treatment is prescribed if deviations in health indicators are detected.
Prognosis and prevention
Laurence-Moon-Bardet-Biedl syndrome refers to incurable pathologies, but with early initiation of therapy, it is possible to significantly improve the quality of life of patients, prevent life-threatening complications. A less optimistic prognosis is in the presence of severe congenital malformations resulting from multiple organ failure. To prevent the disease, couples with burdened heredity are shown medical and genetic counseling during family planning.