Recent Medical Discoveries Of Fibrodysplasia Ossificans Progressiva Disease

Achondroplasia is when cartilage during development is not developed into bone, which results in dwarfism. This condition also characterized by short limbs is initiated by a gain of function mutation in the FGFR3 gene. This mutation is a point mutation. When this mutation occurs, the receptor of the FGF does not need the FGF signal to be activated. This causes the chondrocytes to stop dividing and start differentiating into cartilage prematurely and the bones fail to grow to their proper length, thus resulting in the short limbs that result from this mutation. (textbook) The FGFR3 gene encodes for the Fibroblast growth factor receptor 3 protein. Textbook

Osteopetrosis is a rare, genetic disease that causes extremely dense and brittle bones. This is because individuals affected with osteopetrosis do not have normal osteoclasts, which bones need to work correctly. Healthy bones require properly functioning osteoblasts and osteoclasts. Osteoblasts are responsible for making new bones and osteoclasts are bone cells that are responsible for bone resorption, which is the breaking down of bones and providing space for new bone marrow to grow. An individual with osteopetrosis has osteoclasts that do not function properly, therefore their bones are not healthy (Stocks, Wang, Thompson, Stocks, & Horwitz, 1998).

Fibrodysplasia ossificans progressiva also known as FOP is a one of the rarest, most disabling genetic bone conditions known to medicine. FOP causes muscles, tendons, ligaments, and other connective tissues to turn in to bone. Movement becomes limited in the affected areas of the body. People with FOP typically have malformed toes at birth, meaning the big toe is typically shorter than normal and abnormally turned outward in a position called a valgus deviation. Symptoms of FOP start to show up in early childhood. Most people with FOP develop painful tumor-like swellings also known as fibrous nodules. The fibrous nodules are visible on the neck, shoulders, and back.

Over 90 percent of osteogenesis imperfecta cases are caused by mutations in the COL1A1 and COL1A2 genes. These are the genes that provide instructions for making the proteins that are used to build type I collagen—the most abundant protein in bone, skin, and other connective tissues that provide strength, support, and structure to the body. Osteogenesis imperfecta type I is most often caused by mutations in the COL1A1 gene; specifically, genetic changes that reduce the production of type I collagen. This causes bones to be very brittle and fracture easily. As for OI types II, III, and IV, mutations in the COL1A1 and COL1A2 causes alterations in the structure of type I collagen molecules. This defect will weaken connective tissues, predominantly in bone, and result in the typical features of OI. The mutations in the CRTAP and P3H1 genes cause the rare and sometimes severe cases of osteogenesis imperfecta. CRTAP usually classifies type VII, and P3H1 classifies type VIII. The proteins that are produced by these genes work together to create the mature form of collagen molecules. The defects in these molecules lead to weakened connective tissues, which cause severe bone abnormalities and growth problems. Osteogenesis imperfecta types V and VII are found in people without identified mutations in their genes, making the cause of the disorder unknown. Researchers are continually working towards

By definition, Fibrodysplasia Ossificans Progressiva is: “rare genetic disorder in which the fibrous tissues, muscles, and periosteal regions undergo progressive ossification.” (Mankin, 2009, p. 169)

Fibrodysplasia Ossificans Progressiva is a rare disease that over activates osteogenesis, or bone formation. The disease may also be referred to as “the stone man” disease because it essentially leads to the stiffening of the body, causing restricted mobility. Overall, the predisposition for fibrodysplasia is extremely low for individuals worldwide, as it only affects 1 in 2 million people (10). There seems to be no clear correlation of demographics of people suffering from FOP; the genetic disorder occurs randomly. However, those who live with the disorder face a difficult predicament.

Stickler Syndrome , hereditary progressive arthro-opthalmopathy, is a connective tissue disorder that affects fibrillar collagen. It is a syndrome that effects the patients eyes, hearing, mouth, and joints. Stickler Syndrome is a genetic disorder of connective tissue that causes problems with development. Dr. Gunnar B. Stickler was the first scientist to describe the syndrome that we now know today as Stickler. The diagnosis of Stickler Syndrome is clinically based, and the first diagnosed case was discovered in 1965. Diagnostic criteria has been proposed for Type I Stickler Syndrome, but it has not yet been validated. The criteria are based on assigning points to patients based on their family history, clinical features, and molecular data. Any individual who scores greater than or equal

The article opens with a brief statement regarding a type of conditions termed “vanishing bone” syndrome. When a person suffers from a vanishing bone syndrome, osteolysis may occur. Ostelysis is a condition in which bone may disappear or be destroyed in a pathological manner. It takes place naturally within the body, due to a genetic mutation. Winchester syndrome was one of the initial forms of vanishing bone syndrome to be recognized. Two sisters suffered from the disease whose parents were phenotypically healthy, first cousins. Both of the girls suffered from severe osteolysis. Their condition affected the digits, major joints, heart, eyes, gums, and other various aspects of the musculoskeletal system.

The anatomical problems of FOP are visibly present in all cases. The most common deformity is the curvature of the spinal column; it can be bent anteriorly at 90 degrees and also bent posteriorly at upwards to 50 degrees (raredisease.org). The arms of the human skeleton can be abducted or adducted contingent upon the position the arm is in when the muscles are ossified. The joints will become locked, most commonly the mandible (jaw bone) and coxal joint, as well as the joints of the elbow, knee, and ankle (iofpa.org). As the skeletal muscles ossify, the skeleton can take numerous shapes and malformations, which they are contingent upon what position the body part is in when the muscle is ossified (rarediseases.org). As a person infected with

Fibrous Dysplasia is caused by a gene mutation of chromosome 20 that results in absent or rare osteoblasts and/or osteoclasts. The mutation occurs during the early stages of fetal development, and is not hereditary.

There are numerous factors that contribute to the development of this horrible disease, but the most important factor is vitamin D deficiency. When the minerals in osteoid crystallize, they require adequate concentration of calcium and phosphate. When the concentration is not at the correct level, ossification does not proceed normally (Huether & McCance, 2008). Vitamin D regulates the absorption of calcium from the intestine. When there is a lack of vitamin D, the concentration of calcium begins to fall (Huether & McCance, 2008). The body begins to regulate this calcium drop by increases the amount of PTH synthesis and secretion (Huether & McCance, 2008). An increase of PTH causes a clearance of phosphate and without the correct levels of phosphate mineralization of the bones cannot proceed in the correct manor (Huether & McCance, 2008). The abnormality of bone growth can occur in spongy and compact bone (Mayo

Dwarfism is a syndrome where a person has abnormal bone development. Symptoms include short stature, bowed legs, curvature of the lower spine, and a prominent forehead. The most common type of dwarfism, Achondroplasia, is characterized by a glycine to arginine mutation on codon 380 in the fibroblast growth factor receptor transmembrane domain 3 gene. When the mutated fibroblast growth factor receptor 3 protein interacts with a fibroblast growth factor ligand, the receptor is stabilized and a cascade of events occur. Downstream receptor pathways that are affected by the mutation involve signal transducer and activator of transcription 1 and phospholipase C, gamma 1. Different mutations on the fibroblast growth factor receptor transmembrane

Nail Patella syndrome (NPS) is an autosomal dominant disorder. This means that it can get “passed down”. Disorders like NPS can be passed down through only one parent. The syndrome can affect the tissues of the ectodermal layer, meaning the skin tissues and it can also affect the mesodermal layer, meaning the inner layer of an embryo (JCR: Journal of Clinical Rheumatology). NPS also may affect the renal, skeletal, and ocular parts the body. The syndrome affects the LMX1B gene, this is located on the 9th chromosome. Mutations on the 9th chromosome can result in iliac horns. These iliac horns are horn-like mutations to the pelvis. This occurs in 70% of the people affected by Nail-Patella syndrome. Another

Hypophosphatemia is a condition where a person has low levels of phosphate in their blood. This condition occurs when the enzyme, Alkaline Phosphatase (AP), functions irregularly and causes a reduction in enzymatic activity. This reduced enzyme activity results in issues with the retention of phosphate and calcium in bones caused by Fanconi syndrome. Due to this irregular enzyme activity, the density of the bones decreases since the excess calcium and phosphate aren’t properly included into the new bone by the osteoblasts. However, cases have emerged in which patients have a mutation in the protein sequence of their AP enzyme, and their AP enzyme still properly work, along with their bone density being normal. Since the AP enzyme still works

Achondroplasia is caused by an abnormal gene located on one of the chromosome 4 pair (humans have 23 pairs of chromosomes). It is a result of an autosomal dominant mutation in the fibroblast growth factor receptor gene 3 (FGFR3), which causes an abnormality of cartilage formation. FGFR3 normally has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones.