New lethal disease involving type I and III collagen defect resembling geroderma osteodysplastica, De Barsy syndrome, and Ehlers-Danlos syndrome IV

• Published in: Journal of medical genetics Vol. 35; no. 6; pp. 513 - 518
• Main Authors: Jukkola, A, Kauppila, S, Risteli, L, Vuopala, K, Risteli, J, Leisti, J, Pajunen, L
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.06.1998; BMJ; BMJ Publishing Group LTD
• Subjects: Adult; Aging, Premature; Biological and medical sciences; Cells, Cultured; Collagen - biosynthesis; Collagen - genetics; Collagen Diseases - diagnosis; Collagen Diseases - genetics; Collagen Diseases - metabolism; Connective Tissue Diseases - diagnosis; Connective Tissue Diseases - genetics; Connective Tissue Diseases - metabolism; Diagnosis, Differential; Ehlers-Danlos Syndrome - diagnosis; Fatal Outcome; Female; Humans; Infant; Male; Medical sciences; Peptide Fragments - blood; Procollagen - blood; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin - metabolism; Skin - pathology; Skin - ultrastructure; Human; New syndrome; Connective tissue disease; Skin disease; Nervous system diseases; Elastic tissue disease; Osteodysplastic gerodermia; Diseases of the osteoarticular system; Clinical form; Exploration; Biochemistry; Lethal character; Differential diagnostic; Genetic disease; Case study; Phenotype; Collagen; Ehlers Danlos syndrome; Systemic disease; De Barsy syndrome; Complex syndrome; Child
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.35.6.513

We describe the clinical findings and biochemical features of a male child suffering from a so far undescribed lethal connective tissue disorder characterised by extreme hypermobility of the joints, lax skin, cataracts, severe growth retardation, and insufficient production of type I and type III procollagens. His features are compared with Ehlers-Danlos type IV, De Barsy syndrome, and geroderma osteodysplastica, as these disorders show some symptoms and signs shared with our patient. The child died because of failure of the connective tissue structures joining the skull and the spine, leading to progressive spinal stenosis. The aortic valve was translucent and insufficient. The clinical symptoms and signs, together with histological findings, suggested a collagen defect. Studies on both skin fibroblast cultures and the patient's serum showed reduced synthesis of collagen types I and III at the protein and RNA levels. The sizes of the mRNAs and newly synthesised proteins were normal, excluding gross structural abnormalities. These findings are not in accordance with any other collagen defect characterised so far.