COL2A1 Gene

Spondyloepimetaphyseal dysplasia, Strudwick type is an inherited disorder of bone growth that results in short stature (dwarfism), skeletal abnormalities, and problems with vision. This condition affects the bones of the spine (spondylo-) and two regions (epiphyses and metaphyses) near the ends of long bones in the arms and legs. The Strudwick type was named after the first reported patient with the disorder.

People with this condition have short stature from birth, with a very short trunk and shortened limbs. Their hands and feet, however, are usually average-sized. Affected individuals may have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). This abnormal spinal curvature may be severe and can cause problems with breathing. Instability of the spinal bones (vertebrae) in the neck may increase the risk of spinal cord damage. Other skeletal features include flattened vertebrae (platyspondyly), severe protrusion of the breastbone (pectus carinatum), an abnormality of the hip joint that causes the upper leg bones to turn inward (coxa vara), and an inward- and upward-turning foot (clubfoot). Arthritis may develop early in life.

People with spondyloepimetaphyseal dysplasia, Strudwick type have mild changes in their facial features. Some infants are born with an opening in the roof of the mouth (a cleft palate) and their cheekbones may appear flattened. Eye problems that can impair vision are common, such as severe nearsightedness (high myopia) and tearing of the lining of the eye (retinal detachment).

Spondyloperipheral dysplasia is a disorder that impairs bone growth. This condition is characterized by flattened bones of the spine (platyspondyly) and unusually short fingers and toes (brachydactyly), with the exception of the first (big) toes. Other skeletal abnormalities associated with spondyloperipheral dysplasia include short stature, shortened long bones of the arms and legs, exaggerated curvature of the lower back (lordosis), and an inward- and upward-turning foot (clubfoot). Additionally, some affected individuals have nearsightedness (myopia), hearing loss, and intellectual disability.

Legg-Calvé-Perthes disease is a bone disorder that affects the hips. Usually, only one hip is involved, but in about 10 percent of cases, both hips are affected. Legg-Calvé-Perthes disease begins in childhood, typically between ages 4 and 8, and affects boys more frequently than girls.

In this condition, the upper end of the thigh bone, known as the femoral head, breaks down. As a result, the femoral head is no longer round and does not move easily in the hip socket, which leads to hip pain, limping, and restricted leg movement. The bone eventually begins to heal itself through a normal process called bone remodeling, by which old bone is removed and new bone is created to replace it. This cycle of breakdown and healing can recur multiple times. Affected individuals are often shorter than their peers due to the bone abnormalities. Many people with Legg-Calvé-Perthes disease go on to develop a painful joint disorder called osteoarthritis in the hips at an early age.

Kniest dysplasia is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities and problems with vision and hearing.

People with Kniest dysplasia are born with a short trunk and shortened arms and legs. Adult height ranges from 42 inches to 58 inches. Affected individuals have abnormally large joints that can cause pain and restrict movement, limiting physical activity. These joint problems can also lead to arthritis. Other skeletal features may include a rounded upper back that also curves to the side (kyphoscoliosis), severely flattened bones of the spine (platyspondyly), dumbbell-shaped bones in the arms and legs, long and knobby fingers, and an inward- and upward-turning foot (clubfoot).

Individuals with Kniest dysplasia have a round, flat face with bulging and wide-set eyes. Some affected infants are born with an opening in the roof of the mouth called a cleft palate. Infants may also have breathing problems due to weakness of the windpipe. Severe nearsightedness (myopia) and other eye problems are common in Kniest dysplasia. Some eye problems, such as tearing of the back lining of the eye (retinal detachment), can lead to blindness. Hearing loss resulting from recurrent ear infections is also possible.

Achondrogenesis is a group of severe disorders that affect cartilage and bone development. These conditions are characterized by a small body, short limbs, and other skeletal abnormalities. As a result of serious health problems, infants with achondrogenesis usually die before birth, are stillborn, or die soon after birth from respiratory failure. However, some infants have lived for a short time with intensive medical support.

Researchers have described at least three forms of achondrogenesis, designated as type 1A, type 1B, and type 2. The types are distinguished by their signs and symptoms, inheritance pattern, and genetic cause. However, types 1A and 1B are often hard to tell apart without genetic testing.

Achondrogenesis type 1A, which is also called the Houston-Harris type, is the least well understood of the three forms. Affected infants have extremely short limbs, a narrow chest, short ribs that fracture easily, and a lack of normal bone formation (ossification) in the skull, spine, and pelvis.

Achondrogenesis type 1B, also known as the Parenti-Fraccaro type, is characterized by extremely short limbs, a narrow chest, and a prominent, rounded abdomen. The fingers and toes are short and the feet may turn inward and upward (clubfeet). Affected infants frequently have a soft out-pouching around the belly-button (an umbilical hernia) or near the groin (an inguinal hernia).

Infants with achondrogenesis type 2, which is sometimes called the Langer-Saldino type, have short arms and legs, a narrow chest with short ribs, and underdeveloped lungs. This condition is also associated with a lack of ossification in the spine and pelvis. Distinctive facial features include a prominent forehead, a small chin, and, in some cases, an opening in the roof of the mouth (a cleft palate). The abdomen is enlarged, and affected infants often have a condition called hydrops fetalis, in which excess fluid builds up in the body before birth.

Czech dysplasia is an inherited condition that affects joint function and bone development. People with this condition have joint pain (osteoarthritis) that begins in adolescence or early adulthood. The joint pain mainly affects the hips, knees, shoulders, and spine and may impair mobility. People with Czech dysplasia often have shortened bones in their third and fourth toes, which make their first two toes appear unusually long. Affected individuals may have flattened bones of the spine (platyspondyly) or an abnormal spinal curvature, such as a rounded upper back that also curves to the side (kyphoscoliosis). Some people with Czech dysplasia have progressive hearing loss.

Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals.

A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This appearance results from underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features called Pierre Robin sequence is also common in people with Stickler syndrome. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). This combination of features can lead to feeding problems and difficulty breathing.

Many people with Stickler syndrome have severe nearsightedness (high myopia). In some cases, the clear gel that fills the eyeball (the vitreous) has an abnormal appearance, which is noticeable during an eye examination. Other eye problems are also common, including increased pressure within the eye (glaucoma), clouding of the lens of the eyes (cataracts), and tearing of the lining of the eye (retinal detachment). These eye abnormalities cause impaired vision or blindness in some cases.

In people with Stickler syndrome, hearing loss varies in degree and may become more severe over time. The hearing loss may be sensorineural, meaning that it results from changes in the inner ear, or conductive, meaning that it is caused by abnormalities of the middle ear.

Most people with Stickler syndrome have skeletal abnormalities that affect the joints. The joints of affected children and young adults may be loose and very flexible (hypermobile), though joints become less flexible with age. Arthritis often appears early in life and may cause joint pain or stiffness. Problems with the bones of the spine (vertebrae) can also occur, including abnormal curvature of the spine (scoliosis or kyphosis) and flattened vertebrae (platyspondyly). These spinal abnormalities may cause back pain.

Researchers have described several types of Stickler syndrome, which are distinguished by their genetic causes and their patterns of signs and symptoms. In particular, the eye abnormalities and severity of hearing loss differ among the types. Type I has the highest risk of retinal detachment. Type II also includes eye abnormalities, but type III does not (and is often called non-ocular Stickler syndrome). Types II and III are more likely than type I to have significant hearing loss. Types IV, V, and VI are very rare and have each been diagnosed in only a few individuals.

A condition similar to Stickler syndrome, called Marshall syndrome, is characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Marshall syndrome can also include short stature. Some researchers have classified Marshall syndrome as a variant of Stickler syndrome, while others consider it to be a separate disorder.

Platyspondylic lethal skeletal dysplasia, Torrance type is a severe disorder of bone growth. People with this condition have very short arms and legs, underdeveloped pelvic bones, and unusually short fingers and toes (brachydactyly). This disorder is also characterized by flattened spinal bones (platyspondyly) and an exaggerated curvature of the lower back (lordosis). Infants with this condition are born with a small chest with short ribs that can restrict the growth and expansion of the lungs.

As a result of these serious health problems, some affected fetuses do not survive to term. Infants born with platyspondylic lethal skeletal dysplasia, Torrance type usually die at birth or shortly thereafter from respiratory failure. A few affected people with milder signs and symptoms have lived into adulthood.

Spondyloepiphyseal dysplasia congenita is an inherited bone growth disorder that results in short stature (dwarfism), skeletal abnormalities, and problems with vision and hearing. This condition affects the bones of the spine (spondylo-) and the ends (epiphyses) of long bones in the arms and legs. Congenita indicates that the condition is present from birth.

People with spondyloepiphyseal dysplasia congenita have short stature from birth, with a very short trunk and neck and shortened limbs. Their hands and feet, however, are usually average-sized. Adult height ranges from 3 feet to just over 4 feet. Abnormal curvature of the spine (kyphoscoliosis and lordosis) becomes more severe during childhood. Instability of the spinal bones (vertebrae) in the neck may increase the risk of spinal cord damage. Other skeletal features include flattened vertebrae (platyspondyly); an abnormality of the hip joint that causes the upper leg bones to turn inward (coxa vara); a foot deformity called a clubfoot; and a broad, barrel-shaped chest. Abnormal development of the chest can cause problems with breathing. Arthritis and decreased joint mobility often develop early in life.

People with spondyloepiphyseal dysplasia congenita have mild changes in their facial features. The cheekbones close to the nose may appear flattened. Some infants are born with an opening in the roof of the mouth (a cleft palate). Severe nearsightedness (high myopia) is common, as are other eye problems that can impair vision. About one quarter of people with this condition have hearing loss.

Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals.

A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This appearance results from underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features called Pierre Robin sequence is also common in people with Stickler syndrome. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). This combination of features can lead to feeding problems and difficulty breathing.

Many people with Stickler syndrome have severe nearsightedness (high myopia). In some cases, the clear gel that fills the eyeball (the vitreous) has an abnormal appearance, which is noticeable during an eye examination. Other eye problems are also common, including increased pressure within the eye (glaucoma), clouding of the lens of the eyes (cataracts), and tearing of the lining of the eye (retinal detachment). These eye abnormalities cause impaired vision or blindness in some cases.

In people with Stickler syndrome, hearing loss varies in degree and may become more severe over time. The hearing loss may be sensorineural, meaning that it results from changes in the inner ear, or conductive, meaning that it is caused by abnormalities of the middle ear.

Most people with Stickler syndrome have skeletal abnormalities that affect the joints. The joints of affected children and young adults may be loose and very flexible (hypermobile), though joints become less flexible with age. Arthritis often appears early in life and may cause joint pain or stiffness. Problems with the bones of the spine (vertebrae) can also occur, including abnormal curvature of the spine (scoliosis or kyphosis) and flattened vertebrae (platyspondyly). These spinal abnormalities may cause back pain.

Researchers have described several types of Stickler syndrome, which are distinguished by their genetic causes and their patterns of signs and symptoms. In particular, the eye abnormalities and severity of hearing loss differ among the types. Type I has the highest risk of retinal detachment. Type II also includes eye abnormalities, but type III does not (and is often called non-ocular Stickler syndrome). Types II and III are more likely than type I to have significant hearing loss. Types IV, V, and VI are very rare and have each been diagnosed in only a few individuals.

A condition similar to Stickler syndrome, called Marshall syndrome, is characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Marshall syndrome can also include short stature. Some researchers have classified Marshall syndrome as a variant of Stickler syndrome, while others consider it to be a separate disorder.

Nonsyndromic hearing loss is a partial or total loss of hearing that is not associated with other signs and symptoms. In contrast, syndromic hearing loss occurs with signs and symptoms affecting other parts of the body.

Nonsyndromic hearing loss can be classified in several different ways. One common way is by the condition's pattern of inheritance: autosomal dominant (DFNA), autosomal recessive (DFNB), X-linked (DFNX), or mitochondrial (which does not have a special designation). Each of these types of hearing loss includes multiple subtypes. DFNA, DFNB, and DFNX subtypes are numbered in the order in which they were first described. For example, DFNA1 was the first type of autosomal dominant nonsyndromic hearing loss to be identified.

The characteristics of nonsyndromic hearing loss vary among the different types. Hearing loss can affect one ear (unilateral) or both ears (bilateral). Degrees of hearing loss range from mild (difficulty understanding soft speech) to profound (inability to hear even very loud noises). The term "deafness" is often used to describe severe-to-profound hearing loss. Hearing loss can be stable, or it may be progressive, becoming more severe as a person gets older. Particular types of nonsyndromic hearing loss show distinctive patterns of hearing loss. For example, the loss may be more pronounced at high, middle, or low tones.

Most forms of nonsyndromic hearing loss are described as sensorineural, which means they are associated with a permanent loss of hearing caused by damage to structures in the inner ear. The inner ear processes sound and sends the information to the brain in the form of electrical nerve impulses. Less commonly, nonsyndromic hearing loss is described as conductive, meaning it results from changes in the middle ear. The middle ear contains three tiny bones that help transfer sound from the eardrum to the inner ear. Some forms of nonsyndromic hearing loss, particularly a type called DFNX2, involve changes in both the inner ear and the middle ear. This combination is called mixed hearing loss.

Depending on the type, nonsyndromic hearing loss can become apparent at any time from infancy to old age. Hearing loss that is present before a child learns to speak is classified as prelingual or congenital. Hearing loss that occurs after the development of speech is classified as postlingual.