TRPV4 Gene

Metatropic dysplasia is a skeletal disorder characterized by short stature (dwarfism) with other skeletal abnormalities. The term "metatropic" is derived from the Greek word "metatropos," which means "changing patterns." This name reflects the fact that the skeletal abnormalities associated with the condition change over time.

Affected infants are born with a narrow chest and unusually short arms and legs with dumbbell-shaped long bones. Beginning in early childhood, people with this condition develop abnormal side-to-side and front-to-back curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). The curvature worsens with time and tends to be resistant to treatment. Because of the severe kyphoscoliosis, affected individuals may ultimately have a very short torso in relation to the length of their arms and legs.

Some people with metatropic dysplasia are born with an elongated tailbone known as a coccygeal tail; it is made of a tough but flexible tissue called cartilage. The coccygeal tail usually shrinks over time. Other skeletal problems associated with metatropic dysplasia include flattened bones of the spine (platyspondyly); excessive movement of spinal bones in the neck that can damage the spinal cord; either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum); and joint deformities called contractures that restrict the movement of joints in the shoulders, elbows, hips, and knees. Beginning early in life, affected individuals can also develop a degenerative form of arthritis that causes joint pain and further restricts movement.

The signs and symptoms of metatropic dysplasia can vary from relatively mild to life-threatening. In the most severe cases, the narrow chest and spinal abnormalities prevent the lungs from expanding fully, which restricts breathing. Researchers formerly recognized several distinct forms of metatropic dysplasia based on the severity of the condition's features. The forms included a mild type, a classic type, and a lethal type. However, all of these forms are now considered to be part of a single condition with a spectrum of overlapping signs and symptoms.

Charcot-Marie-Tooth disease encompasses a group of disorders called hereditary sensory and motor neuropathies that damage the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Damage to the peripheral nerves that worsens over time can result in alteration or loss of sensation and wasting (atrophy) of muscles in the feet, legs, and hands.

Charcot-Marie-Tooth disease usually becomes apparent in adolescence or early adulthood, but onset may occur anytime from early childhood through late adulthood. Symptoms of Charcot-Marie-Tooth disease vary in severity and age of onset even among members of the same family. Some people never realize they have the disorder because their symptoms are so mild, but most have a moderate amount of physical disability. A small percentage of people experience severe weakness or other problems which, in very rare cases, can be life-threatening. In most affected individuals, however, Charcot-Marie-Tooth disease does not affect life expectancy.

Typically, the earliest symptoms of Charcot-Marie-Tooth disease result from muscle atrophy in the feet. Affected individuals may have foot abnormalities such as high arches (pes cavus), flat feet (pes planus), or curled toes (hammer toes). They often have difficulty flexing the foot or walking on the heel of the foot. These difficulties may cause a higher than normal step (steppage gait) and increase the risk of ankle injuries and tripping. As the disease worsens, muscles in the lower legs usually weaken, but leg and foot problems rarely require the use of a wheelchair.

Affected individuals may also develop weakness in the hands, causing difficulty with daily activities such as writing, fastening buttons, and turning doorknobs. People with Charcot-Marie-Tooth disease typically experience a decreased sensitivity to touch, heat, and cold in the feet and lower legs, but occasionally feel aching or burning sensations. In rare cases, affected individuals have loss of vision or gradual hearing loss that sometimes leads to deafness.

There are several types of Charcot-Marie-Tooth disease, which are differentiated by their effects on nerve cells and patterns of inheritance. Type 1 (CMT1) is characterized by abnormalities in myelin, the fatty substance that covers nerve cells, protecting them and helping to transmit nerve impulses. These abnormalities slow the transmission of nerve impulses and can affect the health of the nerve fiber. Type 2 (CMT2) is characterized by abnormalities in the fiber, or axon, that extends from a nerve cell body to muscles or to sense organs. These abnormalities reduce the strength of the nerve impulse. In forms of Charcot-Marie-Tooth disease classified as intermediate type, the nerve impulses are both slowed and reduced in strength, probably due to abnormalities in both myelin and axons. Type 4 (CMT4) is distinguished from the other types by its pattern of inheritance; it can affect either the axons or the myelin. Type X Charcot-Marie-Tooth disease (CMTX) is caused by mutations in genes on the X chromosome, one of the two sex chromosomes. Within the various types of Charcot-Marie-Tooth disease, subtypes (such as CMT1A, CMT1B, CMT2A, CMT4A, and CMTX1) indicate different genetic causes.

Sometimes other, historical names are used to refer to particular forms of Charcot-Marie-Tooth disease. For example, Roussy-Levy syndrome is a form of CMT11 with the additional feature of rhythmic shaking (tremors). Dejerine-Sottas syndrome is a term sometimes used to describe a severe, early childhood form of Charcot-Marie-Tooth disease; it is also sometimes called type 3 (CMT3). Depending on the specific gene that is altered, this severe, early-onset form of the disorder may also be classified as CMT1 or CMT4. CMTX5 is also known as Rosenberg-Chutorian syndrome.