RPGRIP1L Gene

Joubert 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.

The hallmark feature of Joubert syndrome is a combination of brain abnormalities that together are known as the molar tooth sign, which can be seen on brain imaging studies such as magnetic resonance imaging (MRI). This sign results from the abnormal development of structures near the back of the brain, including the cerebellar vermis and the brainstem. The molar tooth sign got its name because the characteristic brain abnormalities resemble the cross-section of a molar tooth when seen on an MRI.

Most infants with Joubert syndrome have low muscle tone (hypotonia) in infancy, which contributes to difficulty coordinating movements (ataxia) in early childhood. Other characteristic features of the condition include episodes of unusually fast (hyperpnea) or slow (apnea) breathing in infancy, and abnormal eye movements (ocular motor apraxia). Most affected individuals have delayed development and intellectual disability, which can range from mild to severe. Distinctive facial features can also occur in Joubert syndrome; these include a broad forehead, arched eyebrows, droopy eyelids (ptosis), widely spaced eyes (hypertelorism), low-set ears, and a triangle-shaped mouth.

Joubert syndrome can include a broad range of additional signs and symptoms. The condition is sometimes associated with other eye abnormalities (such as retinal dystrophy, which can cause vision loss, and coloboma, which is a gap or split in a structure of the eye), kidney disease (including polycystic kidney disease and nephronophthisis), liver disease, skeletal abnormalities (such as the presence of extra fingers and toes), or hormone (endocrine) problems. A combination of the characteristic features of Joubert syndrome and one or more of these additional signs and symptoms once characterized several separate disorders. Together, those disorders were referred to as Joubert syndrome and related disorders (JSRD). Now, however, any instances that involve the molar tooth sign, including those with these additional signs and symptoms, are usually considered Joubert syndrome.

Meckel syndrome is a disorder with severe signs and symptoms that affect many parts of the body. The most common features are enlarged kidneys with numerous fluid-filled cysts; an occipital encephalocele, which is a sac-like protrusion of the brain through an opening at the back of the skull; and the presence of extra fingers and toes (polydactyly). Most affected individuals also have a buildup of scar tissue (fibrosis) in the liver.

Other signs and symptoms of Meckel syndrome vary widely among affected individuals. Numerous abnormalities of the brain and spinal cord (central nervous system) have been reported in people with Meckel syndrome, including a group of birth defects known as neural tube defects. These defects occur when a structure called the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. Meckel syndrome can also cause problems with development of the eyes and other facial features, heart, bones, urinary system, and genitalia.

Because of their serious health problems, most individuals with Meckel syndrome die before or shortly after birth. Most often, affected infants die of respiratory problems or kidney failure.