distal arthrogryposis type 2B

Distal Arthrogryposis Type 2B (DA2B)

Distal arthrogryposis type 2B, also known as Sheldon-Hall syndrome, is a genetic disorder characterized by joint contractures in the hands and feet. This condition is part of a larger group of disorders known as distal arthrogryposis syndromes.

Key Features:

• Joint deformities (contractures) that restrict movement in the hands and feet
• Clenched fist, overlapping fingers, camptodactyly, ulnar deviation, and positional foot deformities from birth
• Facial dysmorphism may also be present

Genetic Heterogeneity: Distal arthrogryposis type 2B is caused by heterozygous mutation in the TNNI2 gene on chromosome 11p15. This condition is inherited in an autosomal-dominant fashion, meaning that a single copy of the mutated gene is sufficient to cause the disorder.

Variability: Marked inter- and intrafamilial variability has been reported, indicating that the severity and presentation of DA2B can vary significantly between individuals and even within families.

References:

• [1] Distal arthrogryposis type 2B1 (DA2B1) is characterized by congenital contractures of the distal limb joints and facial dysmorphism. (Source: OMIM)
• [11] Sheldon-Hall syndrome, also known as distal arthrogryposis type 2B, is a disorder characterized by joint deformities that restrict movement in the hands and feet. (Source: Various medical sources)

Distal arthrogryposis type 2B, also known as Sheldon-Hall syndrome, is a disorder characterized by joint deformities (contractures) that restrict movement in the hands and feet. The signs and symptoms of this condition can vary from person to person, but some common features include:

• Clenched fist: A characteristic feature of distal arthrogryposis type 2B, where the fingers are clenched tightly.
• Overlapping fingers: In some cases, the fingers may overlap each other due to contractures.
• Camptodactyly: This refers to a flexion deformity in one or more fingers, making it difficult to extend them fully.
• Ulnar deviation: The hands and feet may be deviated towards the ulnar side (the side away from the center of the body).
• Positional foot deformities: The feet may have abnormal positions or shapes due to contractures.

In addition to these physical characteristics, individuals with distal arthrogryposis type 2B may also experience:

• Limited or absent movement in the affected joints
• Contractures that restrict movement and flexibility in the hands and feet

It's essential to note that the severity of symptoms can vary widely among individuals, even within the same family. Some people may have mild symptoms, while others may experience more severe contractures.

References:

[1] - Distal arthrogryposis type 2B is a clinically and genetically heterogeneous disorder characterized by clenched fist, overlapping fingers, camptodactyly, ulnar deviation, and positional foot deformities from birth. (Source: [3]) [2] - The most common universal symptom is limited or absent movement around small and large joints (contractures). (Source: [5]) [3] - Distal arthrogryposis type 2B Synonyms ... Distal, Type 2B. Summary. Distal arthrogryposis is a clinically and genetically heterogeneous disorder characterized by clenched fist, overlapping fingers, camptodactyly, ulnar deviation, and positional foot deformities from birth. (Source: [14]) [4] - Non-surgical Treatment ... (AMC) varies based on the signs and symptoms presented in each person and the severity of the condition. (Source: [15])

Diagnostic Tests for Distal Arthrogryposis Type 2B

Distal arthrogryposis type 2B, also known as Sheldon-Hall syndrome, is a rare genetic disorder characterized by joint deformities and contractures. Diagnostic tests are essential to confirm the diagnosis and rule out other conditions.

Available Diagnostic Tests:

• Mutation scanning of select exons: This test involves analyzing specific genes (MYH3, TNNT3, TNNI2, or TPM2) for known disease-causing mutations [5].
• Deletion/duplication analysis: This test detects deletions or duplications in the MYH3 gene, which is associated with distal arthrogryposis type 2B [24].
• Sequence analysis of the entire coding region: This comprehensive test analyzes the entire coding region of the MYH3 gene to identify any mutations [53].
• Targeted variant analysis: This test focuses on detecting specific variants in the MYH3, TNNT3, TNNI2, or TPM2 genes associated with distal arthrogryposis type 2B [7].

Other Diagnostic Approaches:

• Skeletal muscle biopsy: Although not a specific diagnostic test for distal arthrogryposis type 2B, skeletal muscle biopsy can help rule out other conditions, such as myopathies or dystrophies [9].
• Clinical molecular genetics testing: This comprehensive approach involves analyzing the entire coding region of the MYH3 gene and is offered by MedGene [12].

Important Considerations:

• DNA diagnostic tests are not yet readily available to distinguish between various congenital myopathies and/or dystrophies.
• Marked inter- and intrafamilial variability has been reported in distal arthrogryposis type 2B, making diagnosis challenging [13].
• Abnormalities of fast-twitch muscles are seen in many types of distal arthrogryposis, highlighting the need for comprehensive diagnostic testing [14].

References:

[5] Mutation scanning of select exons [7] Targeted variant analysis [9] Skeletal muscle biopsy [12] Clinical molecular genetics testing [13] Distal arthrogryposis type 2B2 (DA2B2) [14] Abnormalities of fast twitch muscles in distal arthrogryposis

Treatment Options for Distal Arthrogryposis Type 2B

Distal arthrogryposis type 2B, also known as Sheldon-Hall syndrome, is a rare genetic disorder characterized by joint deformities (contractures) that restrict movement in the hands and feet. While there is no completely successful approach to treat this condition, various treatment options are available to manage its symptoms.

Acetylcholine Treatment

Recent studies have shown that acetylcholine treatment, combined with physical therapy, may elicit a response from some patients with distal arthrogryposis type 2B [2]. This treatment approach aims to improve muscle function and mobility in affected individuals.

Capsulotomy

Another surgical option for treating distal arthrogryposis type 2B is capsulotomy, which involves making an incision in the joint capsule to improve passive elbow flexion, active flexion by triceps, or both [1], [7]. This procedure can help alleviate contractures and improve mobility.

Rehabilitation

Rehabilitation, including occupational therapy and physiotherapy, is a crucial aspect of managing distal arthrogryposis type 2B. The goal of rehabilitation is to maintain and maximize function, as well as prevent further joint deformities [9].

While these treatment options may provide some relief for patients with distal arthrogryposis type 2B, it's essential to note that each individual's response to treatment can vary greatly.

References:

[1] Axt et al. (no date) - cited in [7]

[2] (no author) Jul 11, 2024

[7] by D Desai · 2020 · Cited by 33

[9] (no author) Sep 11, 2024

Differential Diagnosis of Distal Arthrogryposis Type 2B (DA2B)

Distal Arthrogryposis Type 2B (DA2B) is a rare genetic disorder characterized by congenital contractures of the distal joints of the limbs without a primary neurological defect. Establishing a differential diagnosis for DA2B involves considering other conditions that may present with similar symptoms.

Key Differential Diagnoses:

• Distal Arthrogryposis Type 1 (DA1): This condition is characterized by congenital contractures of the distal joints, but it often presents with facial and other organ system involvement. DA2B can be distinguished from DA1 by its lack of facial and other organ system involvement.
• Freeman-Sheldon Syndrome (FSS): FSS is a rare genetic disorder that shares features with DA2B, including congenital contractures of the distal joints. However, FSS often presents with characteristic craniofacial abnormalities and other systemic features.
• Multiple Pterygium Syndromes: These syndromes are characterized by webbing or pterygia of the skin, which can be mistaken for DA2B. However, multiple pterygium syndromes typically present with more severe contractures and a higher risk of mortality.

Other Differential Diagnoses:

• Cerebroculofacioskeletal Syndrome: This rare genetic disorder presents with congenital contractures, craniofacial abnormalities, and other systemic features.
• Pena Shokier Syndrome: This syndrome is characterized by congenital contractures, craniofacial abnormalities, and other systemic features.

Clinical Features:

DA2B typically presents with clenched fists at birth, distal joint contractures, and normal intelligence. The differential diagnosis for DA2B should consider the presence or absence of facial and other organ system involvement, as well as the severity of contractures.

References:

• Bamshad M. Mutations in TNNT3 cause multiple congenital contractures: a second locus for distal arthrogryposis type 2B. Am J Hum Genet. 2003;72(5):1131-1138.
• Krakowiak et al. Distal Arthrogryposis Type 2B (DA2B) was described by Krakowiak et al when it was separated from the Freeman-Sheldon syndrome.

Note: The references provided are a selection of relevant studies and should not be considered an exhaustive list.