TRIM32 Gene

Limb-girdle muscular dystrophy is a term for a group of diseases that cause weakness and wasting of the muscles in the arms and legs. The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs.

The severity, age of onset, and features of limb-girdle muscle dystrophy vary among the many subtypes of this condition and may be inconsistent even within the same family. Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild.

In the early stages of limb-girdle muscular dystrophy, affected individuals may have an unusual walking gait, such as waddling or walking on the balls of their feet, and may also have difficulty running. They may need to use their arms to press themselves up from a squatting position because of their weak thigh muscles. As the condition progresses, people with limb-girdle muscular dystrophy may eventually require wheelchair assistance.

Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) "stick out" from the back, a sign known as scapular winging. Affected individuals may also have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Overgrowth (hypertrophy) of the calf muscles occurs in some people with limb-girdle muscular dystrophy.

Weakening of the heart muscle (cardiomyopathy) occurs in some forms of limb-girdle muscular dystrophy. Some affected individuals experience mild to severe breathing problems related to the weakness of muscles needed for breathing. In some cases, the breathing problems are severe enough that affected individuals need to use a machine to help them breathe (mechanical ventilation).

Intelligence is generally unaffected in limb-girdle muscular dystrophy; however, developmental delay and intellectual disability have been reported in rare forms of the disorder.

Bardet-Biedl syndrome is a disorder that affects many parts of the body. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.

Vision loss is one of the major features of Bardet-Biedl syndrome. Loss of vision occurs as the light-sensing tissue at the back of the eye (the retina) gradually deteriorates. Problems with night vision become apparent by mid-childhood, followed by blind spots that develop in the side (peripheral) vision. Over time, these blind spots enlarge and merge to produce tunnel vision. Most people with Bardet-Biedl syndrome also develop blurred central vision (poor visual acuity) and become legally blind by adolescence or early adulthood.

Obesity is another characteristic feature of Bardet-Biedl syndrome. Abnormal weight gain typically begins in early childhood and continues to be an issue throughout life. Complications of obesity can include type 2 diabetes, high blood pressure (hypertension), and abnormally high cholesterol levels (hypercholesterolemia).

Other major signs and symptoms of Bardet-Biedl syndrome include the presence of extra fingers or toes (polydactyly), intellectual disability or learning problems, and abnormalities of the genitalia. Most affected males produce reduced amounts of sex hormones (hypogonadism), and they are usually unable to father biological children (infertile). Many people with Bardet-Biedl syndrome also have kidney abnormalities, which can be serious or life-threatening.

Additional features of Bardet-Biedl syndrome can include impaired speech, delayed development of motor skills such as standing and walking, behavioral problems such as emotional immaturity and inappropriate outbursts, and clumsiness or poor coordination. Distinctive facial features, dental abnormalities, unusually short or fused fingers or toes, and a partial or complete loss of the sense of smell (anosmia) have also been reported in some people with Bardet-Biedl syndrome. Additionally, this condition can affect the heart, liver, and digestive system.