#130010
ICD+
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| EHLERS-DANLOS SYNDROME, TYPE II | ||||||||||||||||||||||||||||||||||||
| Alternative titles; symbols | ||||||||||||||||||||||||||||||||||||
| EHLERS DANLOS SYNDROME, MILD CLASSIC TYPE EDS II EDS2 EHLERS DANLOS SYNDROME, MITIS TYPE | ||||||||||||||||||||||||||||||||||||
| Phenotype Gene Relationships | ||||||||||||||||||||||||||||||||||||
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| Clinical Synopsis | ||||||||||||||||||||||||||||||||||||
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| A number sign (#) is used with this entry because Ehlers-Danlos syndrome type II can be caused by mutations in the COL5A1 (120215) and COL5A2 (120190) genes. Mutations in the same genes can cause EDS I (130000). | ||||||||||||||||||||||||||||||||||||
| Description | ||||||||||||||||||||||||||||||||||||
| The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders that share the common features of skin hyperextensibility, articular hypermobility, and tissue fragility (Beighton, 1993). In the Villefranche classification of EDS (Beighton et al., 1998), 6 main descriptive types were substituted for earlier types numbered with Roman numerals: classic type (EDS I and EDS II), hypermobility type (EDS III, 130020), vascular type (EDS IV, 130050), kyphoscoliosis type (EDS VI, 225400), arthrochalasia type (EDS VIIA and VIIB, 130060), and dermatosparaxis type (EDS VIIC, 225410). Six other forms were listed, including a category of 'unspecified forms.' Major and minor diagnostic criteria were defined for each type and complemented whenever possible with laboratory findings. The main features of classic Ehlers-Danlos syndrome (EDS I and EDS II) are loose-jointedness and fragile, bruisable skin that heals with peculiar 'cigarette-paper' scars (Beighton, 1993). | ||||||||||||||||||||||||||||||||||||
| Clinical Features | ||||||||||||||||||||||||||||||||||||
| EDS II has all the stigmata of EDS I (see 130000), but to a minor degree, and some patients may easily remain undiagnosed. Joint laxity is limited and may be confined to the hands and feet. Skin involvement is less evident. Prematurity does not occur more frequently than normal. Mitral valve prolapse is rare (summary by Steinmann et al., 2002). Loughlin et al. (1995) stated that EDS II is probably the commonest variant of the Ehlers-Danlos syndrome. De Felice et al. (2001) studied 4 patients with EDS II and 8 patients with EDS III (130020), the hypermobile type. They concluded that absence of the inferior labial frenulum and the lingual frenulum are characteristics of EDS. Absence of the inferior labial frenulum showed 100% sensitivity and 99.4% specificity; absence of the lingual frenulum showed 71.4% sensitivity and 100% specificity. Wenstrup et al. (2002) performed a prospective cohort study on 71 consecutive EDS patients. Twenty of 71, or 28%, had aortic root dilatation defined as greater than 2 serum deviations above population-based norms. Fourteen of 42 individuals with the classic form of EDS (types I and II) and 6 of 29 individuals with the hypermobile form (type III) had aortic root dilatation, with no gender differences. Wenstrup et al. (2002) concluded that aortic root dilatation is a common finding in EDS. However, rates of progression and complication are unknown. | ||||||||||||||||||||||||||||||||||||
| Inheritance | ||||||||||||||||||||||||||||||||||||
| EDS II is an autosomal dominant disorder (De Paepe et al., 1997). | ||||||||||||||||||||||||||||||||||||
| Cytogenetics | ||||||||||||||||||||||||||||||||||||
| Scarbrough et al. (1984) described what they considered to be EDS II in a 14-year-old male with an unbalanced t(6;13). The karyotype was designated as 45,XY,-6,-13,+der(6),t(6;13)(q27;q11). The patient was monosomic for 13pter-q11 and for a small part of 6q27 (the most distal segment of 6q). Joint hypermobility, velvety skin, several well-healed, parchment-like scars over both shins, and mild propensity for bruising were described. The patient had serious neuropsychiatric problems. | ||||||||||||||||||||||||||||||||||||
| Mapping | ||||||||||||||||||||||||||||||||||||
| Using an intragenic simple sequence repeat polymorphism of the COL5A1 gene (120215) as a linkage marker, Loughlin et al. (1995) showed linkage to EDS II; maximum lod = 8.3 at theta = 0.00 in a single large pedigree. The COL5A1 gene is located on 9q34.2-q34.3. Greenspan et al. (1995) used 3-prime untranslated region RFLPs to exclude the COL5A1 gene as a candidate in families with Ehlers-Danlos syndrome type II. The reason for inconsistency with the findings of Loughlin et al. (1995) may be the genetic heterogeneity of EDS II. Burrows et al. (1996) observed tight linkage of the COL5A1 locus to a mixed Ehlers-Danlos syndrome type I/II in a 3-generation family. A lod score of 4.07 at zero recombination was calculated. The variation in expression in this family suggested that EDS types I and II are allelic, and the linkage data supported the hypothesis that mutation in COL5A1 can cause both phenotypes. | ||||||||||||||||||||||||||||||||||||
| Molecular Genetics | ||||||||||||||||||||||||||||||||||||
| De Paepe et al. (1997) demonstrated a heterozygous splicing mutation in the COL5A1 gene (120215.0005) in a father and 2 sons with type II EDS. Richards et al. (1998) demonstrated a missense mutation in the COL5A2 gene (120190.0003) in a mother and her 2 sons with type II EDS. | ||||||||||||||||||||||||||||||||||||
| See Also: | ||||||||||||||||||||||||||||||||||||
| Beighton (1970) | ||||||||||||||||||||||||||||||||||||
| REFERENCES | ||||||||||||||||||||||||||||||||||||
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