Beals syndrome is a rare monogenic disease, clinically similar to Marfan syndrome, which occurs due to a violation of the structure of connective tissue. It has an autosomal dominant type of inheritance. Pathology is manifested by articular contractures, multiple anomalies of the skeleton structure, specific deformation of the auricle by the type of “crumpled” ear. For diagnosis, a molecular genetic study is prescribed, instrumental imaging methods are carried out (X-ray of the skeleton, CT of the joints, ultrasound of the heart). Treatment includes vitamin-mineral and energotropic drugs, physiotherapy, massage and physical therapy.
Q68.8 Other specified congenital musculoskeletal deformities
Beals syndrome (congenital contractural arachnodactyly) was named after the American physician Rodney Beals, who, together with his colleague Frederick Hecht, described typical clinical symptoms in 1971. The genetic nature of the pathology was established in 1994. Due to the rare occurrence, the frequency of the disease in the population is not known. To date, about 120 cases of Biles syndrome have been described in the literature. Despite this, the problem does not lose its relevance due to the difficulty of making a correct diagnosis, the lack of etiopathogenetic methods of therapy.
The disease has a monogenic nature — it occurs when the FBN2 gene is defective, which is located on the 5th chromosome at the 5q23-q31 locus and encodes the synthesis of the fibrillin-2 protein. With Beals syndrome, inheritance occurs according to an autosomal dominant type: if one of the parents has a disease, the risk of having a sick child is 50%, therefore all known cases are of a family nature.
The syndrome is caused by a structural pathology of the fibrillin-2 protein, which consists of 2889 amino acids and is responsible for the construction of the extracellular matrix of connective tissue. Normally, the maximum expression of this protein is observed in the first trimester of pregnancy, when the entire embryo tissue is laid and differentiated. In patients with Bils disease, the structure of bone tissue and the assembly of elastic fibers are disrupted.
The deformation of connective tissue is manifested by multiple anomalies of the skeleton structure. In addition, damaged fibrillin-2 is expressed in the structures of the eyeball, organs of the cardiovascular system, causing congenital malformations. The pathogenetic features of the disease are similar to Marfan syndrome, in which the formation of fibrillin-1 is disrupted, therefore diagnostic errors are not excluded.
Manifestations of Biles syndrome are determined in the child immediately after childbirth. Funnel-shaped deformity of the chest, clubfoot, curvature and deviation of the fingers towards the little finger (ulnar deviation) are noticeable. A typical feature is thin, excessively long fingers — the so-called “spider fingers”, or arachnodactyly. Pathologies of the facial skeleton include dolichocephaly, a high protruding forehead, and a Gothic palate.
A pathognomonic sign of the Bils symptom is a “crumpled ear” — deformities of the auricles, which manifest themselves in chaotically arranged folds resembling a crumpled sheet of paper. The lesion of the musculoskeletal system is characterized by multiple contractures of the joints. Elbow and knee joints, small interphalangeal joints are most often affected.
About 15-20% of patients, in addition to pathologies of the structure of the bone system, face anomalies of internal organs. Typical disorders are identical to those in Marfan syndrome: aortic aneurysm, violation of the structure of arteries and veins of medium caliber, heart defects (additional chords, defects of the atrial or interventricular septum, damage to the valvular apparatus). A characteristic sign of Biles’ disease is a subluxation of the lens.
Bone lesions in most patients tend to reverse development with proper rehabilitation measures, but in some patients they steadily progress. Such people face a significant decrease in the volume of active movements, physical development disorders, and in particularly severe cases, disability is established due to movement restrictions.
Beals syndrome is characterized by vivid clinical symptoms from the moment of birth of the child, however, due to its similarity to Marfan syndrome and the higher prevalence of the latter, errors in diagnosis are possible. The patient is examined by a pediatrician (neonatologist) together with a geneticist, a pediatric orthopedic traumatologist, and a cardiologist. The diagnostic plan includes the following methods:
- Genetic testing. Molecular genetic analysis to detect FBN2 mutation is the only way to confirm the diagnosis with 100% accuracy, to differentiate pathology with Marfan disease. The study is done both in the postnatal period and prenatally if one of the future parents suffers from contractural arachnodactyly.
- Radiography of the skeleton. To clarify the degree of bone curvature, an X-ray examination of the limbs, spine, and skull is shown. Radiography of joints with contractures, CT or MRI of joints is also performed for more accurate diagnosis.
- EchoCG. To confirm or exclude congenital heart defects, ultrasound examination is used, which shows in detail the structure of the organ. ECG and Holter monitoring are used to comprehensively examine the cardiovascular system. If necessary, CT or MRI of the heart is prescribed.
- Consultation of an ophthalmologist. Given the high prevalence of eye defects in Biles’ disease, ophthalmoscopy and visual acuity assessment are recommended. To study the degree of lens displacement, ultrasound biomicroscopy and biometrics of the eye are performed. Additionally, intraocular pressure is measured.
Etiopathogenetic therapy of Beals syndrome has not been developed. Medical care is reduced to the appointment of symptomatic medications, comprehensive rehabilitation, regular dynamic monitoring of the patient by specialized specialists. Treatment of the disease begins at an early age, immediately after diagnosis, and includes the following areas:
- Metabolic therapy. To normalize the pace of physical development, improve muscle strength, drugs with levocarnitine are used. To strengthen bone tissue, active metabolites of vitamin D are used in combination with calcium supplements, osteogenone.
- Physical therapy. To increase mobility in the joints, increase the volume of active movements, improve coordination, physical therapy is recommended. Classes are often supplemented with massage, which helps to normalize muscle tone, improves blood supply and energy exchange in soft tissues. Shock wave therapy, electrophoresis, and UHF therapy show a good effect in joint contractures. To eliminate muscle spasms, relieve pain and discomfort, balneotherapy, paraffin or ozokerite applications are carried out.
Patients with Biles syndrome are subject to dispensary observation by a group of specialists: a pediatrician (therapist), specialized orthopedic doctors, a cardiologist, an ophthalmologist. The frequency of examinations is on average 1-2 times a year, according to indications, the number of professional examinations is increasing. If you feel well, a spa treatment is prescribed, which has a good restorative effect on the body.
Consultation of a cardiac surgeon is recommended for patients with congenital anomalies of the heart and large vessels, which may require surgical correction. With complicated forms of lens subluxation, the help of ophthalmic surgeons is necessary: phacoemulsification, implantation of an intraocular lens.
Prognosis and prevention
With timely initiation of treatment, joint contractures can be reduced or leveled, which has a positive effect on the quality of life of patients. The prognosis is favorable in most cases, but the presence of congenital cardiovascular defects worsens the prospects. Prevention of Biles syndrome involves medical and genetic counseling of people in whose family there have been cases of the disease, prenatal diagnosis.