Beals-Hecht Syndrome

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Introduction

Beals-Hecht syndrome, also known as congenital contractural arachnodactyly, is caused by a defect in fibrillin as in Marfan syndrome. This syndrome is characterized by a multitude of clinical findings including arachnodactyly, narrow body habitus, scoliosis, congenital contractures, and external ear deformities. Restrictive lung disease may be associated with the severe scoliosis and thoracic cage abnormalities in this syndrome. We describe a child with Beals-Hecht syndrome and review the literature.

Congenital Contractural Arachnodactyly (CCA, Beals syndrome) is a rare congenital connective tissue disorder. As with Marfan’s syndrome, people with CCA typically have an arm span that is greater than their height and very long fingers and toes. However, Beals and Hecht discovered in 1972 that, unlike Marfan’s, CCA is caused by mutations to the FBN2 gene.

Beals syndrome is an autosomal-dominant connective tissue disorder, characterized by multiple flexion contractures, arachnodactyly, severe kyphoscoliosis, crumpled ear, and muscular hypoplasia. It has similarities to Marfan syndrome (MFS) in many respects. It has much fewer incidences of eye and heart anomalies compared with MFS. Beals syndrome is caused by a mutation in the fibrillin-2 gene (FBN2) in 5q23; MFS is caused by mutations in fibrillin-1. With time, there is spontaneous improvement in joint contractures, but kyphosis tends to be progressive.

The neonatal form results from new mutations and tends to be severe. Prenatal molecular diagnosis is possible. Ultrasound could be used to demonstrate hypokinesia and joint contractures in presumptive cases. We present a case of a patient with Beals syndrome who presented to the emergency department with pneumonia and was found to have narrowing of the foramen magnum, with partial fusion of C2-C3 vertebral bodies. To our knowledge, this has not been documented in the literature and could be characteristic in relation to Beals syndrome.

Congenital contractural arachnodactyly (CCA) is a genetic disorder that is characterized by tall height; skinny, long limbs; long, skinny fingers and toes (arachnodactyly); multiple joint deformities present at birth (congenital contractures), usually of the elbows, knees, hips, fingers and ankles; “crumpled”-looking ears; and curvature of the spine (kyphoscoliosis). Enlargement (dilation) of the aorta and other features might also be present in some affected people.

CCA is caused by mutations in a gene called FBN2 gene and is inherited in an autosomal dominant pattern. CCA shares similiar signs and symptoms to Marfan syndrome; however, Marfan syndrome is not caused by mutations in the FBN2 gene. Treatment includes physical therapy or surgery for joint contractures, bracing and/or surgery for kyphoscoliosis, and standard management of aortic root dilation.

Beals syndrome is an extremely rare genetic disorder characterized by the permanent fixation of certain joints (e.g., fingers, elbows, knees, and hips) in a flexed position (contractures); abnormally long, slender fingers and toes (arachnodactyly); permanently flexed fingers (camptodactyly); and/or abnormally shaped ears resulting in a “crumpled” appearance.

In addition, affected individuals may exhibit front-to-back and side-to-side curvature of the spine (kyphoscoliosis); feet that are abnormally positioned (talipes equinovarus or clubfoot); outward displacement of the fingers (ulnar deviation of the fingers); an abnormally short neck; and/or. Rarely, affected individuals may have a slight deformity of the valve on the left side of the heart (mitral valve prolapse). Beals syndrome is inherited as an autosomal dominant trait.

Congenital contractural arachnodactyly (Beals syndrome) is an autosomal dominantly inherited connective tissue disorder characterized by multiple flexion contractures, arachnodactyly, severe kyphoscoliosis, abnormal pinnae and muscular hypoplasia. It is caused by a mutation in FBN2 gene on chromosome 5q23. Although the clinical features can be similar to Marfan syndrome (MFS), multiple joint contractures (especially elbow, knee and finger joints), and crumpled ears in the absence of significant aortic root dilatation are characteristic of Beals syndrome and rarely found in Marfan syndrome.

The incidence of CCA is unknown and its prevalence is difficult to estimate considering the overlap in phenotype with MFS; the number of patients reported has increased following the identification of FBN2 mutation. Molecular prenatal diagnosis is possible. Ultrasound imaging may be used to demonstrate joint contractures and hypokinesia in suspected cases. Management of children with CCA is symptomatic. Spontaneous improvement in camptodactyly and contractures is observed but residual camptodactyly always remains. Early intervention for scoliosis can prevent morbidity later in life. Cardiac evaluation and ophthalmologic evaluations are recommended.

Symptoms

CCA is characterized by contractures of varying degrees, mainly involving the large joints, which are present in all affected children at birth. The contractures may be mild and tend to improve over time, but permanently bent fingers and toes (camptodactyly) are almost always present. In addition to long fingers and toes and a tall, slender body, people with CCA often have ears that appear to be crumpled, joint stiffness, and underdeveloped muscles (muscular hypoplasia), and they may have curved spines (congenital kyphoscoliosis). If kyphoscoliosis is present, it often becomes progressively worse and may require surgery. In some cases, the blood vessel that distributes blood from the heart to the rest of the body (aorta) may be abnormally enlarged (aortic root dilatation).

The features of congenital contractural arachnodactyly (CCA) vary from person to person, both within and between families. The classic form is characterized by.

  • Marfan-like appearance (tall and slender with arm span longer than the person’s height)
  • Arachnodactyly (long slender fingers and toes)
  • “Crumpled” ears
  • Contractures of major joints from birth (particularly knees, elbows, fingers, toes, and hips)
  • Bowed long bones
  • Muscular hypoplasia (underdeveloped muscles)
  • Kyphosis/scoliosis
  • Aortic root dilation
  • Craniofacial abnormalities (such as micrognathia; high arched palate; scaphocephaly (premature fusion of the sagittal suture of the skull leading to a long, narrow head); brachycephaly (premature fusion of the coronal suture, leading to a short skull); and frontal bossing).

Severe forms of CCA are very rare, with very few reported cases. In addition to the typical skeletal findings (arachnodactyly, joint contractures, and scoliosis) and abnormally shaped ears, infants with the severe/lethal form have many cardiovascular and gastrointestinal abnormalities.

 

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

  • Congenital contractural arachnodactyly, (CCA);
  • Beals syndrome;
  • Beals-Hecht syndrome;
  • Arthrogryposis, distal, type 9.

Causes

Congenital Contractural Arachnodactyly may be the result of new mutations in the FBN2 gene or it may be inherited from a parent in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Congenital contractural arachnodactyly (CCA) is caused by mutations in the FBN2 gene. The FBN2 gene provides instructions for producing the fibrillin-2 protein. Fibrillin-2 binds to other proteins and molecules to form threadlike filaments called microfibrils. Microfibrils become part of the fibers that provide strength and flexibility to connective tissue.

Additionally, microfibrils hold molecules called growth factors and release them at the appropriate time to control the growth and repair of tissues and organs throughout the body. A mutation in the FBN2 gene can reduce the amount and/or quality of fibrillin-2 that is available to form microfibrils. As a result, decreased microfibril formation weakens the elastic fibers and allows growth factors to be released inappropriately, causing tall stature, deformities of the fingers and toes, and other characteristic features of CCA.

Diagnosis

CCA may be diagnosed through the physical characteristics associated with the disease of long, slender body and contractures of multiple joints, as well as other symptoms, such as muscular hypoplasia. Molecular genetic tests may be run using sequence analysis or deletion/duplication analysis to look for mutations in the FBN2 gene.[6] Prenatal testing may be used for pregnancies with a risk of CCA, such as a parent or sibling with the disease.

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment

Physical therapy for joint contractures helps increase joint mobility and improve the effects of muscle hypoplasia (usually in the calf muscles). In severe cases, surgery may be needed. Since the kyphosis/scoliosis tends to be progressive, bracing and/or surgical correction is often needed. Consultation with an orthopedist is encouraged. Other symptoms, if present, should be addressed as they arise. Regular physician visits should be scheduled to monitor symptom progression and development.

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