Introduction:
Sheldon-Hall syndrome also called distal arthrogryposis type 2B, where “distal” refers to the extremities that are away from the center, and “arthrogryposis”, a Greek word that refers to crooked (gryposis) joints (arthro). Clinical features of this syndrome include mainly hand and foot abnormalities and these features are present at birth and mostly do not get worsen over time. Sheldon-Hall syndrome does not cause abnormalities in other parts of the body except for joints and it does not affect intelligence. There is no cure for Sheldon-Hall syndrome but involves early intervention with physical or occupational therapies. Individuals with Sheldon-Hall syndrome have a normal life expectancy.
What Is Sheldon-Hall Syndrome?
Sheldon-Hall Syndrome is a genetic disorder that is caused by mutations in the genes that are involved in the formation of proteins that are responsible for muscle contraction. This syndrome is characterized by joint contractures that occur due to the stiffening or shortening of tendons, muscles, and tissues which results in the restriction of movements, a triangular face, and a webbed neck.
What Are the Clinical Features of Sheldon-Hall Syndrome?
The clinical features of Sheldon-Hall Syndrome may vary among individuals. Hand and foot abnormalities include:
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Joint contractures.
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Camptodactyly (bent toes and fingers).
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Ulnar deviation, is a hand deformity in which the joints of the wrist and fingers bend outside the forearm or towards the pinky finger.
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Overlapping fingers.
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Clubfoot or talipes equinovarus (a foot abnormality in which the foot is twisted inward and upward).
Facial features include:
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Triangular face.
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Down-slanting palpebral fissures (down-slanting of the areas between the eye).
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Deep nasolabial folds (skin folds between the nose and lips).
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Small mouth.
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Small pointed chin.
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Long philtrum.
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Attached ear lobes.
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High-arched palate.
Other features include:
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Webbed neck (skin folds around the neck).
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Short stature.
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Short neck.
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Delay in development.
What Is the Cause of Sheldon-Hall Syndrome?
Sheldon-Hall syndrome occurs due to mutation in the TNNI2 (troponin I2, fast skeletal type), TNNT3 (troponin T3, fast skeletal type), MYH3 (myosin heavy chain 3), and TPM2 (tropomyosin 2) genes. These genes are responsible for muscle contraction. This gene mutation is inherited in an autosomal dominant pattern, where one copy of the mutated gene is enough to cause the disorder. In about 50 percent of cases, this disease is inherited whereas in the remaining cases, a new mutation can occur where there is no family history of the disorder.
Features of the TNNI2 Gene Include:
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The TNNI2 gene is located on chromosome 11.
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This gene provides information in the production of a protein called troponin I, and this protein is found in skeletal muscles.
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Troponin I, T, and C form the troponin complex which plays an important role in muscle activity.
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The troponin complex along with the calcium helps in regulating muscle contraction.
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The troponin complex is a part of the functional unit of muscle tissue called sarcomeres which contains thick and thin filaments. These filaments bind to each other and then release which causes muscle contraction.
Features of the TPM2 Gene Include:
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This gene provides information in the production of a protein called beta-tropomyosin which belongs to the tropomyosin protein group and these proteins help in regulating muscle contraction by controlling myosin and actin which are muscle proteins.
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In other cells, the tropomyosin protein controls the cell shape.
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Beta-tropomyosin is basically found in skeletal muscles.
Features of the TNNT3 Gene Include:
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This gene is located on chromosome 11.
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This gene provides information in the production of a protein called troponin T which is found in skeletal muscles.
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Troponin T is a part of the troponin complex. Therefore, it plays an important role in muscle contraction.
Features of the MYH3 Gene Include:
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This gene is located on chromosome 17.
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This gene provides information in the formation of a protein called myosin-3 which is part of a group of proteins called as myosins.
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These proteins play an important role in the transportation and movement of materials inside and between the cells.
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The thick filaments in muscle fibers are made up of myosin and the thin filaments are made up of actin and these both filaments are involved in muscle contraction.
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Myosin-3-containing muscle fibers are primarily found in the fetus and play an important role in muscle development.
Any mutation in these genes can interfere with the development of muscles and prevent muscle contractions, which results in contractures and other skeletal abnormalities.
What Is the Diagnosis of Sheldon-Hall Syndrome?
The diagnosis of Sheldon-Hall syndrome involves:
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The diagnosis is based on clinical features such as joint contractures, ulnar deviation, overlapping fingers, triangular face, webbed neck, small mouth, and short stature and a positive family history of Sheldon-Hall syndrome.
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Genetic testing reveals a mutation in the TNNI2, TNNT3, MYH3, or TPM2 genes.
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A prenatal diagnosis with the help of an ultrasound which is done during the 18 to 24 weeks of gestation reveals bone abnormalities and a prenatal molecular genetic diagnosis can be done to confirm the syndrome.
What Is the Differential Diagnosis of Sheldon-Hall Syndrome?
The differential diagnosis of Sheldon-Hall syndrome includes:
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Freeman-Sheldon Syndrome: Freeman-Sheldon syndrome is a type of genetic disorder that occurs due to a mutation in the MYH3 gene and affects the face and skull muscles. In this syndrome, the facial features are not as severe as seen in Sheldon-Hall syndrome. feeding difficulties are present at birth which require surgical treatment and scoliosis (sideward curve of the spine) is present which is not common in Sheldon-Hall syndrome.
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Distal Arthrogryposis 1: It is a type of genetic disorder that occurs due to mutation in the MYBPC1 (myosin binding protein C1) and TPM2 genes. The clinical features of this condition are limited to joint contractures of feet and hands and do not contain any major facial abnormalities.
What Is the Management of Sheldon-Hall Syndrome?
There is no cure for Sheldon-Hall syndrome. Early intervention for joint deformities can improve the condition such as:
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Use of braces, casts, or surgical treatment for correcting limb contractures.
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Physical therapy to improve the movements of hands and limbs.
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Orthopedic management can be done to minimize the contractures and improve walking, and motor function.
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Orthodontic treatment can be done to correct the jaw abnormalities.
Conclusion:
Sheldon-Hall syndrome is a genetic disorder that affects primarily the joints of the hands and feet. Early intervention by using a cast, braces, or surgery can improve the condition. Individuals with this syndrome should undergo genetic counseling because these individuals carry a 50 percent risk to pass down the condition. Individuals with this syndrome have a good life span.
