Distal Arthrogryposis and Lethal Congenital Contracture Syndrome – An Overview

Figures

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  FIGURE 1. Morphological features of distal arthrogryposis. A child born with distal arthrogryposis, showing characteristic camptodactyly, such as one or more fingers permanently bent. The characteristic clubfoot is also seen, as well as the abnormal finger positions of the hand (Modified from Chen, 2015).

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  FIGURE 2. Sarcomere structure containing sarcomeric proteins responsible for proper function. Various regions of titin consisting of Z-disk, I-band, A-band, and M-band. M-line region of titin consists of the titin kinase region (Tk region). In the top panel, known mutations in MYBPC1 gene are listed. Patients with TK mutation (Trp34072Arg) presented dilated cardiomyopathy and DA phenotype. Mutations in Mex-1 Arg34175 and Gln35278* show DCM and joint contractures. Mutations in Mex-2 Ser35469serfs* show DCM and moderate to severe joint contractures. Homozygous 1 base deletion on exon 360 also presents with skeletal muscle disorder and fetal cardiomyopathy.

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  FIGURE 3. Various forms of cardiomyopathies associated with the development of DAs. The different forms of cardiomyopathy caused by different mutations shown in Table 1. These lead to morphological changes in the heart and dysfunction. In the above figure, mutations can lead to hypertrophic heart where the ventricular wall thickens, and the ventricular chamber gets smaller, leading to cardiac dysfunction. In contrast, the dilated heart shows thinner ventricular walls and bigger ventricular chamber, leading to reduced cardiac function. Arrhythmogenic heart is characterized by the presence of fat or fibrous tissue causing abnormal heart rhythms and, in severe cases, sudden cardiac arrest.