Clinical AreaOrthopaedics
Associated diseases
- Acrogigantism, differential diagnosis
- Adams-Oliver syndrome, differential diagnosis
- Akne inversa, familial; differential diagnosis
- Arterial calcification, infantile [generalized]; differential diagnosis
- Arthrogrypose, Differentialdiagnose
- Arthrogryposis, distal; differential diagnosis
- Arthrogryposis, neuromuscular; differential diagnosis
- Arthrogryposis, syndromal; differential diagnosis
- Aymé-Gripp syndrome, differential diagnosis
- Baller-Gerold syndrome, differential diagnosis
- Brachydactyly, differential diagnosis
- Bruck syndrome 1/Kuskokwim syndrome/Bruck syndrome 2
- Calcinosis, tumorous; differential diagnosis
- Campomelic dysplasia, differential diagnosis
- Cartilage-hair hypoplasia / anauxetic dysplasia spectrum, differential diagnosis
- Chondrodysplasia punctata, differential diagnosis
- Chondrodysplasia, metaphyseal; differential diagnosis
- Cleidocranial dysostosis
- Cornelia-de Lange syndrome, differential diagnosis
- Dwarfism, diastrophic
- Dwarfism, idiopathic; differential diagnosis
- Ehlers-Danlos syndromes, differential diagnosis
- Ellis-van-Creveld syndrome, differential diagnosis
- FGFR-craniosynostosis syndrome, differential diagnosis
- Gitelman plus Bartter syndromes, differential diagnosis
- GM1-Gangliosidosis typ I-II, differential diagnosis
- GM1-Gangliosidosis type I-III
- GM1-Gangliosidosis type III, differential diagnosis
- Gorlin syndrome, differential diagnosis
- Greig cephalopolysyndactyly, differential diagnosis
- Hereditary fibrosing poikiloderma-tendon contractures-myopathy-pulmonary fibrosis syndrome, differential diagnosis
- Holt-Oram syndrome, differential diagnosis
- Hyaline fibromatosis syndrome, differential diagnosis
- Hypertrophic osteoarthropathy, primary
- Hypophosphatasia, adult, infantile, perinatal lethal; differential diagnosis
- Jeune syndrome, differential diagnosis
- KBG syndrome
- KBG syndrome, differential diagnosis II
- Kenny-Caffey syndrome 1 + 2
- Kleinwuchs, idiopatisch; SHOX-Gen
- Klippel-Feil syndrome, differential diagnosis
- Larsen syndrome, differential diagnosis
- Léri-Weill syndrome
- Loeys-Dietz-/ Marfan-/ vaskuläres Ehlers-Danlos-Syndrom, Differentialdiagnose
- Lupus [erythematosus], "monogenic"; differential diagnosis
- Lupus erythematodes, susceptibility
- Marfan syndrome, differential diagnosis
- Morbus Bechterew
- Morbus Paget [of bone], differential diagnosis
- Movement disorders, adult onset; differential diagnosis
- Multiple epiphysäre Dysplasie, Differentialdiagnose
- Multiple pterygium syndrome, lethal; differential diagnosis
- Myhre syndrome, differential diagnosis
- Nasu-Hakola disease, differential diagnosis
- Osteoarthropathy, primary hypertrophic; differential diagnosis
- Osteochondritis dissecans, differential diagnosis
- Osteochondromas
- Osteochondromas, multiple; differential diagnosis
- Osteogenesis imperfecta, differential diagnosis
- Osteopathia striata - cranial sclerosis, differential diagnosis
- Osteopetrosis, differential diagnosis
- Osteoporosis, monogenic; differential diagnosis
- Pallister-Hall syndrome, differential diagnoses
- Parathyroid cancer, differential diagnosis
- Peroxisome biogenesis disorders, large panel; differential diagnosis
- Poly-/syndactyly, pre- + postaxial; differential diagnosis
- Pseudohypoparathyreoidism, pseudopseudohypoparathyreoidism
- Rickets, hypophosphataemic; differential diagnosis
- Robinow syndrome, AD/XLR; differential diagnosis
- Robinow syndrome, autosomal recessive
- Schwartz-Jampel syndrome, differential diagnosis
- Scoliosis, early onset; differential diagnosis
- Sensenbrenner syndrome, differential diagnosis
- Short stature, idiopathic, familial; SHOX gene
- Short-rib thoracic dysplasia. differential diagnosis
- Skeletal dysplasia, differential diagnosis
- Skeletal dysplasia, recessive; differential diagnosis
- Small stature, differential diagnosis
- Spondylocarpotarsal synostosis, differential diagnosis
- Spondyloepimetaphyseal dysplasia, differential diagnosis
- Stickler syndrome, differential diagnosis I
- Stickler syndrome, differential diagnosis II; enlargement panel
- Synspondylism
- Thanatophoric dysplasia, differential diagnosis
- Thoracic dystrophies, differential diagnosis
- Ulna-mamma syndrome
- Weill-Marchesani syndrome 1-4, differential diagnosis
Notes on the clinical area
Here you will find the disease-related gene panels available for the clinical area specified above.
If you cannot find the disease you are looking for, please use a known synonym in the search (also in English).
Orthopedics
Molecular genetic diagnostics are also used in orthopaedics to clarify the hereditary causes of many of the genetically determined diseases. The aim here is to identify deviations from the reference genome ("wild type") and then, if necessary, to distinguish between neutral variants and pathogenic mutations that are important for the physiological development and undisturbed function of bones, joints and soft tissues. The inheritance patterns of genetically determined diseases are the basis of genetic counselling for patients, persons at risk and affected families. Over the past 30 years, hundreds of genes that cause hereditary diseases or contribute to the development of genetic disorders have been successively characterised. Current results of genetic research have a direct impact on the diagnostic procedure in the laboratory and in genetic counselling. For example, mutations in independent genes on different chromosomes can cause clinically indistinguishable syndromes (genetic heterogeneity in the various forms of skeletal dysplasia with >300 different mutated genes). On the other hand, different mutations in one and the same gene lead to clinically clearly separated disease entities (mutated COL1A1 genes lead to four different osteogenesis imperfecta types and/or to Ehlers-Danlos syndrome [Arthrochalasia type 1]).
Formal genetics and etiology
Formal genetically and etiologically, the following groups of genetic diseases can be distinguished:
- monogenic diseases (autosomal or X-chromosomal inheritance)
- mitochondrial diseases (maternal or autosomal inheritance)
- multifactorial diseases (interaction of several to many genes plus environmental factors)
Congenital malformations
Congenital malformations of bones and joints often appear sporadically - is there a genetic (co-)cause? Many inherited orthopaedic conditions have been proven to be based on genetic changes and lead to disorders in the proteins that build bone and soft tissue. DNA diagnostics therefore often involves a step-by-step procedure in which the most frequent mutations are first tested before the very rare genetic causes are also identified in parallel approaches using comprehensive and more cost-intensive panel procedures. Mutations found or all variants with unclear significance (VUS) are verified by DNA sequence analysis using Sanger technology.
Ehlers-Danlos syndrome
The differential diagnosis of Ehlers-Danlos syndrome (as well as the clinically sometimes difficult to discern Loeys-Dietz syndrome) also includes Marfan syndrome, a rare congenital disease caused by mutation of the FBN1 gene, among other instances. The formation of fibrillin or microfibrillin is disturbed, which is responsible for the stability, strength and elasticity of connective tissue. Cracks and stretch marks appear in the skin in addition to myopia and lens opacity. The consequences in the further developments in Marfan syndrome concern the affected heart and blood vessels, possibly with aortic rupture as the most frequent cause of death.
Arthrogryposis
The terms arthrogryposis and arthrogryposis multiplex congenital (AMC) do not describe a uniform diagnosis in a heterogeneous group of rare syndromal diseases. The common feature is a lack of fetal motility in utero. More than 300 specific diseases with arthrogryposis features have been described and include neuromuscular diseases, skeletal dysplasias, multiple syndromes with congenital anomalies. The exact differential diagnosis is ultimately often based on molecular genetic findings only. Causes of arthrogryposis are genetic and environmental factors. Genetic causes include individual genetic defects (autosomal dominant, recessive, X-linked and mitochondrial mutations). More than 35 specific genetic disorders have been identified associated with AMC.