Camurati–Engelmann disease (CED) is a very rare

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

that causes characteristic anomalies in the

skeleton A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...

. It is also known as progressive diaphyseal dysplasia. It is a form of

dysplasia Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs (macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopic ...

. Patients typically have heavily thickened bones, especially along the

shafts ''Shafts'' was an English feminist magazine produced by Margaret Sibthorp from 1892 until 1899. Initially published weekly and priced at one penny, its themes included votes for women, women's education, and radical attitudes towards vivisection, ...

of the

long bone The long bones are those that are longer than they are wide. They are one of five types of bones: long, Short bone, short, Flat bone, flat, Irregular bone, irregular and Sesamoid bone, sesamoid. Long bones, especially the femur and tibia, are subj ...

s (called diaphyseal dysplasia). The

skull The skull is a bone protective cavity for the brain. The skull is composed of four types of bone i.e., cranial bones, facial bones, ear ossicles and hyoid bone. However two parts are more prominent: the cranium and the mandible. In humans, the ...

bones may be thickened so that the passages through the

that carry

nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...

s and

blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away ...

s become narrowed, possibly leading to sensory deficits,

blindness Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment� ...

, or

deafness Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is written ...

. This

disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...

often appears in

childhood A child (plural, : children) is a human being between the stages of childbirth, birth and puberty, or between the Development of the human body, developmental period of infancy and puberty. The legal definition of ''child'' generally refers ...

and is considered to be inherited, however many patients have no previous history of CED within their family. The disease is slowly progressive and, while there is no cure, there is treatment. It is named for M. Camurati and G. Engelmann.

Signs and symptoms

Patients with CED complain of chronic bone pain in the legs or arms, muscle weakness (

myopathy In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...

) and experience a waddling gait. Other clinical problems associated with the disease include increased fatigue, weakness, muscle spasms, headache, difficulty gaining weight, and delay in puberty. Some patients have an abnormal or absent

tibia The tibia (; ), also known as the shinbone or shankbone, is the larger, stronger, and anterior (frontal) of the two bones in the leg below the knee in vertebrates (the other being the fibula, behind and to the outside of the tibia); it connects ...

, may present with a

flat foot Flat feet (also called pes planus or fallen arches) is a postural deformity in which the arches of the foot collapse, with the entire sole of the foot coming into complete or near-complete contact with the ground. Sometimes children are born ...

, or

scoliosis Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...

. This disease may also cause bones to become abnormally hardened which is referred to as sclerosis. This hardening may affect the bones at the base of the skull or those in the hands, feet, or jaw. This causes ongoing pain and aching within the body parts that are affected. The pain has been described as either a hot electric stabbing pain, an ever-increasing pressure sensation around the bones (especially before electrical storms) or as a constant ache that radiates through several long bones at once. Pain may also occur in the hips, wrists, knees and other joints as they essentially just 'lock-up' (often becoming very stiff, immobile and sore), mostly when walking up or down staircases, writing for extended periods of time, or during the colder months of the year. Those with the disease tend to have a very characteristic walk medically diagnosed as a 'waddling gait'. This is observed by the broad-based gait with a duck-like waddle to the swing phase, the pelvis drops to the side of the leg being raised, notable forward curvature of the lumbar spine and a marked body swing. The pain is especially severe during a 'flare-up', these can be unpredictable, exhausting and last anywhere from a few hours to several weeks. This is a common occurrence for several CED patients, often causing myopathy and extensive sleep deprivation from the chronic, severe and disabling pain. Patients may even require the use of a wheelchair (or additional carer's help with getting dressed, showering, mobility/shopping, preparing meals or lifting heavy items) especially when bedridden or housebound for days or weeks at a time. 'Flare-ups' may be attributed to, or exacerbated by growth spurts, stress, exhaustion, exercise, standing or walking for too long, illness, infection, being accidentally knocked/hurt or injured, after surgery/anaesthetics, cold weather, electrical storms, and sudden changes in barometric pressure. CED may also affect internal organs, the

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

and

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

, which may become enlarged. A loss of vision and/or hearing can occur if bones are adversely affected by the hardening in the skull. Hence proactive specialist check-ups, X-rays, diagnostic tests/scans, and regular blood tests are recommended on an annual basis to monitor the CED bony growth and secondary medical issues that may arise from this condition.

Cause

Camurati-Engelmann disease is caused by autosomal dominant mutations in the gene TGFB1, localized at chromosome 19q13.

Diagnosis

Classification

There are two forms: * Type 1 is associated with TGFB1 * Type 2 is not associated with TGFB1 Type 1 Camurati-Engelmann Disease is associated with an error occurring in the TGFB1 protein. Affected individuals shared a haplotype between D19S881 to D19S606. TGFB1 protein is encoded by the TGF-B1 gene, which occurs on chromosome 19q13.1-13.3. This protein is responsible for a multitude of functions, one of which includes regulating the function of osteoblasts and osteoclasts, which decreases bone resorption and increases bone formation.Saito, T., Kinoshita, A., Yoshiura, K. I., Makita, Y., Wakui, K., Honke, K., ... & Taniguchi, N. (2001). Domain-specific mutations of a transforming growth factor (TGF)-β1 latency-associated peptide cause Camurati-Engelmann disease because of the formation of a constitutively active form of TGF-β1.Journal of Biological Chemistry, 276(15), 11469-11472. These functions can be affected by a series of mutations that occur on exon 4, near the carboxyl terminus of the latency associated peptide, or LAP. TGFB1 is expressed as a latent form, a mature form and a B1-LAP. Mutations to R218H affect the association of the B1-LAP and the mature form of TGFB1 by conformational changes to B1-LAP. These mutations can lead to a buildup of mature TGFB1, which accumulates in the mutant R218H fibroblasts. Fibroblasts are a type of cell that creates collagen and the extracellular matrix. This suggests that R218H mutation causes a disassociation between mature-TGFB1 and B1-LAP. Mutations at the LLL12-13ins and Y81H regions decrease the secretion of TGFB1, which leads to intracellular buildup of TGFB1. Type 2 Camurati-Engelmann Disease is still speculative, with no distinct evidence to credit its existence. There are many similarities between Type 2 CED and hyperostosis generalisata with striations of the bones (HGS), with some speculating they are two phenotypic variations of the same disease.

Treatment

Camurati–Engelmann disease is somewhat treatable. Glucocorticosteroids, which are anti-inflammatory and immunosuppressive agents, are used in some cases. This form of medication helps in bone strength, however can have multiple side effects. In several reports, successful treatment with glucocoricosteroids was described, as certain side effects can benefit a person with CED. This drug helps with pain and fatigue as well as some correction of radiographic abnormalities. Alternative treatments such as massage, relaxation techniques (meditation, essential oils, spa baths, music therapy, etc.), gentle stretching, and especially heat therapy have been successfully used to an extent in conjunction with pain medications. A majority of CED patients require some form of analgesics, muscle relaxant, and/or sleep inducing medication to manage the pain, specifically if experiencing frequent or severe 'flare-ups' (e.g. during

winter Winter is the coldest season of the year in polar and temperate climates. It occurs after autumn and before spring. The tilt of Earth's axis causes seasons; winter occurs when a hemisphere is oriented away from the Sun. Different cultures ...

).Jadhav, A. T. U. L., & Ghanekar, J. A. I. S. H. R. E. E. (2013). Camurati–Engelmann disease. Indian Journal of Clinical Practice, 24(2).

Notable persons

John Belluso John Belluso (November 13, 1969 – February 10, 2006) was an American playwright best known for his works focusing on the lives of disabled people. He also directed a writing program for disabled people. Early life and education Born in War ...

, writer for the

CBS CBS Broadcasting Inc., commonly shortened to CBS, the abbreviation of its former legal name Columbia Broadcasting System, is an American commercial broadcast television and radio network serving as the flagship property of the CBS Entertainmen ...

television show ''

Ghost Whisperer ''Ghost Whisperer'' is an American supernatural television series, which ran on CBS from September 23, 2005, to May 21, 2010. The series follows the life of Melinda Gordon ( Jennifer Love Hewitt), who has the ability to see and communicate with ...

'', used a wheel chair from the age of 13 because of the Camurati–Engelmann syndrome. He died on February 10, 2006, at the age of 36 in New York City.

References

External links

{{DEFAULTSORT:Camurati-Engelmann Disease Extracellular ligand disorders Skeletal disorders Rare diseases Autosomal dominant disorders