The musculocontractural type of Ehlers-Danlos syndrome is characterized by progressive multisystem fragility-related manifestations, including joint dislocations and deformities; skin hyperextensibility, bruisability, and fragility, with recurrent large subcutaneous hematomas; cardiac valvular, respiratory, gastrointestinal, and ophthalmologic complications; and myopathy, featuring ... The musculocontractural type of Ehlers-Danlos syndrome is characterized by progressive multisystem fragility-related manifestations, including joint dislocations and deformities; skin hyperextensibility, bruisability, and fragility, with recurrent large subcutaneous hematomas; cardiac valvular, respiratory, gastrointestinal, and ophthalmologic complications; and myopathy, featuring muscle hypoplasia, muscle weakness, and an abnormal muscle fiber pattern in histology in adulthood, resulting in gross motor developmental delay (summary by Muller et al., 2013). For a discussion of genetic heterogeneity of the musculocontractural type of Ehlers-Danlos syndrome, see EDSMC1 (601776).
Muller et al. (2013) studied a 2-year-old Indian boy, born of first-cousin parents, who exhibited facial dysmorphism consisting of frontal bossing, open anterior fontanel, downward-slanting palpebral fissures, telecanthus, bluish sclerae, high-arched palate, tent-shaped lips, dental crowding, brachycephaly, and ... Muller et al. (2013) studied a 2-year-old Indian boy, born of first-cousin parents, who exhibited facial dysmorphism consisting of frontal bossing, open anterior fontanel, downward-slanting palpebral fissures, telecanthus, bluish sclerae, high-arched palate, tent-shaped lips, dental crowding, brachycephaly, and prominent ears, as well as arachnodactyly, adducted thumbs, joint hyperlaxity, inguinal hernia, and congenital bilateral talipes equinovarus. Echocardiography showed a patent foramen ovale, and CT scan of the brain revealed generalized mild cerebral atrophy. After clubfoot surgery, the patient had delayed wound healing and atrophic scarring of the skin. Generalized muscle weakness was observed, suggestive of an underlying myopathy, and his gross motor development was delayed. His cognitive development was normal.
In a 2-year-old Indian boy with the musculocontractural type of Ehlers-Danlos syndrome, who was negative for mutation in the CHST14 gene (608429), Muller et al. (2013) performed high-density SNP array genotyping, which revealed 25 homozygous regions exceeding 4 ... In a 2-year-old Indian boy with the musculocontractural type of Ehlers-Danlos syndrome, who was negative for mutation in the CHST14 gene (608429), Muller et al. (2013) performed high-density SNP array genotyping, which revealed 25 homozygous regions exceeding 4 Mb. Sequencing of the functional candidate gene DSE (605942), located within the largest, 44.689-Mb region of homozygosity, revealed a homozygous missense mutation (S268L; 605492.0001). Both parents and a healthy brother were heterozygous for the mutation, which was not found in 300 Caucasian control DNA samples or in the 1000 Genomes Project, dbSNP, or NHLBI Exome Sequencing Project databases.