Arthritis, and Osteosarcoma

Multiple hereditary exostoses (EXT) is an autosomal dominant disorder characterized by multiple projections of bone capped by cartilage, most numerous in the metaphyses of long bones, but also occurring on the diaphyses of long bones. Flat bones, vertebrae, and the ribs may also be affected, but the skull is usually not involved. Deformity of the legs, forearms (resembling Madelung deformity), and hands is frequent (Peterson, 1989).Two conditions in which multiple exostoses occur are metachondromatosis (OMIM ) and the Langer-Giedion syndrome (LGS ); the latter condition is also known as trichorhinophalangeal syndrome type II. Furthermore, exostosis-like lesions occur with fibrodysplasia ossificans progressiva (FOP ), occipital horn syndrome (OMIM ), and the adult stage of hereditary hypophosphatemia (see {307800}); these exostoses are located at sites of tendon and muscle attachment. A relatively rare variant of the supracondylar process, on the anteromedial surface of the distal humerus, can be confused with an exostosis; the variant is said to be present in about 1% of persons of European descent (Silverman, 1985).

EXOSTOSES, MULTIPLE, TYPE I Is also known as multiple cartilaginous exostoses|ext1|multiple osteochondromas|diaphyseal aclasis|ext|osteochondromatosis

• Short stature
• Neoplasm
• Depressivity
• Abnormality of the foot
• Genu valgum

SOURCES: OMIM MENDELIAN

Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis is a type 2 collagen-related bone disorder characterized by precocious, generalized osteoarthritis (with onset as early as childhood) and mild, dysplastic spinal changes (flattening of vertebrae, irregular endplates and wedge-shaped deformities) resulting in a mildly short trunk.

MILD SPONDYLOEPIPHYSEAL DYSPLASIA DUE TO COL2A1 MUTATION WITH EARLY-ONSET OSTEOARTHRITIS Is also known as namaqualand hip dysplasia|nhd

• Intellectual disability
• Short stature
• Pain
• Congestive heart failure
• Pneumonia

SOURCES: OMIM ORPHANET MESH MENDELIAN

Dysspondyloenchondromatosis is a rare skeletal dysplasia characterized by anisospondyly and multiple enchondromas in vertebrae and the metaphyseal and diaphyseal parts of long tubular bones, leading to kyphoscoliosis and lower limb asymmetry.

• Intellectual disability
• Short stature
• Scoliosis
• Delayed skeletal maturation
• Kyphoscoliosis

SOURCES: ORPHANET MENDELIAN

Otospondylomegaepiphyseal dysplasia (OSMED) is characterized by sensorineural deafness and relatively short extremities with abnormally large knees and elbows but normal total body length. The diagnostic radiologic findings are the enlarged epiphyses combined with a moderate platyspondyly, most marked in the lower thoracic region. There are no ocular abnormalities. Patients have typical facial features, including midface hypoplasia (summary by Giedion et al., 1982). Some patients have osteoarthritis (Brunner et al., 1994).

OTOSPONDYLOMEGAEPIPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT; OSMEDA Is also known as osmed, heterozygous|weissenbacher-zweymuller syndrome|pierre robin syndrome with fetal chondrodysplasia stickler syndrome, nonocular type, formerly|stl3, formerly|stickler syndrome, type iii, formerly|wzs

• Hearing impairment
• Micrognathia
• Sensorineural hearing impairment
• Cleft palate
• Myopia

SOURCES: OMIM MENDELIAN

OSTEOGENIC SARCOMA Is also known as osteosarcoma|osrc

• Short stature
• Neoplasm
• Abnormality of metabolism/homeostasis
• Sarcoma
• Osteosarcoma

SOURCES: OMIM ORPHANET MENDELIAN

Nail-patella syndrome (NPS) is a rare hereditary patellar dysostosis characterized by nail hypoplasia or aplasia, aplastic or hypoplastic patellae, elbow dysplasia, and the presence of iliac horns as well as renal and ocular anomalies.

NAIL-PATELLA SYNDROME Is also known as turner-kieser syndrome|onychoosteodysplasia

• Hearing impairment
• Cataract
• Hypertension
• Renal insufficiency
• Glaucoma

SOURCES: ORPHANET MENDELIAN

Paget disease is a metabolic bone disease characterized by focal abnormalities of increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Bone lesions in this disorder show evidence of increased osteoclastic bone resorption and disorganized bone structure. See reviews by Ralston et al. (2008) and Ralston and Albagha (2014). Genetic Heterogeneity of Paget Disease of BoneAlso see PDB2 (OMIM ), caused by mutation in the TNFRSF11A gene (OMIM ) on chromosome 18q21; PDB4 (OMIM ), mapped to chromosome 5q31; PDB5 (OMIM ), caused by mutation in the TNFRSF11B gene (OMIM ) on chromosome 8q24; and PDB6 (OMIM ), caused by mutation in the ZNF687 gene (OMIM ) on chromosome 1q21.Suggestive linkage of a form of PDB to chromosome 6p (PDB1) was reported by Fotino et al. (1977); however, further studies did not confirm linkage to this site (Moore and Hoffman, 1988; Nance et al., 2000; Good et al., 2001).

• Hearing impairment
• Neoplasm
• Pain
• Bone pain
• Osteolysis

SOURCES: OMIM MENDELIAN

Familial osteochondritis dissecans is a rare genetic skeletal disorder characterized clinically by abnormal chondro-skeletal development, disproportionate short stature and skeletal deformation mainly affecting the knees, hips, ankles and elbows with onset generally in late childhood or adolescence.

FAMILIAL OSTEOCHONDRITIS DISSECANS Is also known as osteochondritis dissecans and short stature|od|osteochondritis dissecans, short stature, and early-onset osteoarthritis

• Short stature
• Abnormal facial shape
• Pain
• Depressed nasal bridge
• Brachydactyly

SOURCES: MESH ORPHANET OMIM MENDELIAN

Stickler syndrome type 3 is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by craniofacial dysmorphism (midface hypoplasia, depressed nasal bridge, small nose with upturned tip, cleft palate, Pierre Robin sequence), bilateral, pronounced sensorineural hearing loss, and skeletal/joint anomalies (including spondyloepiphyseal dysplasia, arthralgia/arthropathy), in the absence of ocular abnormalities.

STICKLER SYNDROME TYPE 3 Is also known as stickler syndrome, vitreous type 2|stickler syndrome, beaded vitreous type|stickler syndrome, non-ocular type

• Hearing impairment
• Micrognathia
• Sensorineural hearing impairment
• Cleft palate
• Cataract

SOURCES: OMIM ORPHANET MENDELIAN

Malignant melanoma is a neoplasm of pigment-producing cells called melanocytes that occurs most often in the skin, but may also occur in the eyes, ears, gastrointestinal tract, leptomeninges, and oral and genital mucous membranes (summary by Habif, 2010). Genetic Heterogeneity of Susceptibility to Cutaneous Malignant MelanomaThe locus for susceptibility to familial cutaneous malignant melanoma-1 (CMM1) has been mapped to chromosome 1p36. Other CMM susceptibility loci include CMM2 (OMIM ), caused by variation in the CDKN2A gene (OMIM ) on chromosome 9p21; CMM3 (OMIM ), caused by variation in the CDK4 gene (OMIM ) on chromosome 12q14; CMM4 (OMIM ), mapped to chromosome 1p22; CMM5 (OMIM ), caused by variation in the MC1R gene (OMIM ) on chromosome 16q24; CMM6 (OMIM ), caused by variation in the XRCC3 gene (OMIM ) on chromosome 14q32; CMM7 (OMIM ), mapped to chromosome 20q11; CMM8 (OMIM ), caused by variation in the MITF gene (OMIM ) on chromosome 3p13; CMM9 (OMIM ), caused by variation in the TERT gene (OMIM ) on chromosome 5p15; and CMM10 (OMIM ), caused by mutation in the POT1 gene (OMIM ) on chromosome 7q31.Somatic mutations causing malignant melanoma have also been identified in several genes, including BRAF (OMIM ), STK11 (OMIM ), PTEN (OMIM ), TRRAP (OMIM ), DCC (OMIM ), GRIN2A (OMIM ), ZNF831, BAP1 (OMIM ), and RASA2 (OMIM ). A large percentage of melanomas (40-60%) carry an activating somatic mutation in the BRAF gene, most often V600E ({164757.0001}) (Davies et al., 2002; Pollock et al., 2003).

MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 1; CMM1 Is also known as familial atypical mole-malignant melanoma syndrome|b-k mole syndrome|melanoma, familial|dns|dysplastic nevus syndrome, hereditary|cmm|melanoma, cutaneous malignant|mlm|fammm|melanoma, malignant

• Neoplasm
• Abnormality of the eye
• Retinopathy
• Nevus
• Neoplasm of the skin

SOURCES: OMIM MENDELIAN