Ehlers-Danlos arthrochalasia type (VIIA-B) - expanding the phenotype: from prenatal life through adulthood

• Published in: Clinical genetics 2012-08, Vol.82 (2), p.121-130
• Main Authors: Klaassens, M, Reinstein, E, Hilhorst-Hofstee, Y, Schrander, JJP, Malfait, F, Staal, H, ten Have, LC, Blaauw, J, Roggeveen, HCJ, Krakow, D, De Paepe, A, van Steensel, MAM, Pals, G, Graham, JM, Schrander-Stumpel, CTRM
• Format: Article
• Language: English
• Subjects: (sub)luxations; Adolescent; Adult; Age; Base Sequence; Biological and medical sciences; Child; Child, Preschool; Collagen; Collagen (type I); Collagen Type I - genetics; Danlos syndrome (EDS); Differential diagnosis; Dislocation; EDS type VII; Ehlers; Ehlers-Danlos syndrome; Ehlers-Danlos Syndrome - diagnosis; Exons; Female; Fundamental and applied biological sciences. Psychology; Genes; Genetic disorders; Genetics of eukaryotes. Biological and molecular evolution; Hip; Humans; hypermobility; Infant; Infant, Newborn; Joints; Male; Medical diagnosis; Medical genetics; Medical sciences; Mobility; Molecular and cellular biology; Mutation; Neonates; Pedigree; Phenotype; RNA Splice Sites; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin; the arthrochalasia type EDS; Young Adult
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2011.01758.x

Klaassens M, Reinstein E, Hilhorst‐Hofstee Y, Schrander JJP, Malfait F, Staal H, ten Have LC, Blaauw J, Roggeveen HCJ, Krakow D, De Paepe A, van Steensel MAM, Pals G, Graham JM Jr, Schrander‐Stumpel CTRM. Ehlers–Danlos arthrochalasia types (VIIA–B) – expanding the phenotype: from prenatal life through adulthood. The Ehlers–Danlos syndromes (EDS) form a clinically and genetically heterogeneous group of inherited connective‐tissue disorders characterized by joint hypermobility, tissue fragility and skin abnormalities. Six subtypes have been well characterized based on clinical features and molecular genetic abnormalities. The arthrochalasia type EDS (formerly types VIIA and B) is characterized by severe generalized joint hypermobility with multiple dislocations including congenital bilateral dislocation of the hips, muscular hypotonia and distinct dysmorphic features. The diagnosis of the arthrochalasia type EDS is of importance in the neonatal period because of consequences of physical disability in later life. However, the differential diagnosis may be difficult because of overlap with other hypermobility syndromes. In addition, the significant hypotonia may direct the physician toward various neuromuscular diagnoses. As patients become older, the hypotonia decreases and facial features become less distinct. In this report, we describe seven patients at different ages. Timing of diagnosis varied from prenatal life to adult age. The diagnosis of EDS type VII was confirmed by biochemical studies or mutation analysis showing characteristic mutations in COL1A1 and COL1A2. These mutations result in skipping of exon 6, which leads to defective collagen synthesis. For physicians treating patients with EDS type VII, achieving mobility for the patient is the greatest challenge and it may be impossible because of recurrent dislocations of nearly all joints in severe cases.