SNP Shot: Genomic Insights

Joubert syndrome is a condition that affects various parts of the body, with symptoms differing from person to person, even within the same family.

A defining characteristic of Joubert syndrome is the "molar tooth sign," a combination of brain abnormalities visible on MRI scans. This sign arises from the abnormal development of structures at the back of the brain, specifically the cerebellar vermis and brainstem. The name comes from the resemblance of these abnormalities to the cross-section of a molar tooth on an MRI image.

Most babies with Joubert syndrome have low muscle tone (hypotonia), leading to coordination difficulties (ataxia) in early childhood. Other common features include periods of rapid (hyperpnea) or slow (apnea) breathing in infancy and abnormal eye movements (ocular motor apraxia). Most individuals experience developmental delays and intellectual disability, ranging from mild to severe. Distinctive facial features may also be present, such as a broad forehead, arched eyebrows, droopy eyelids (ptosis), widely spaced eyes (hypertelorism), low-set ears, and a triangle-shaped mouth.

Joubert syndrome can also involve a wider range of symptoms. It is sometimes linked to other eye problems (like retinal dystrophy, causing vision loss, and coloboma, a gap in the eye's structure), kidney disease (including polycystic kidney disease and nephronophthisis), liver disease, skeletal abnormalities (such as extra fingers or toes), or hormone (endocrine) problems. Previously, the combination of Joubert syndrome's core features with these additional signs was used to define several separate disorders, collectively known as Joubert syndrome and related disorders (JSRD). However, currently, any case displaying the molar tooth sign, even with these additional symptoms, is generally classified as Joubert syndrome.

Inheritance:

Joubert syndrome typically follows an autosomal recessive inheritance pattern. This means that an individual must inherit two copies of a mutated gene (one from each parent) to develop the condition. The parents, each carrying one copy of the mutated gene, usually do not exhibit any symptoms.

In rare instances, Joubert syndrome is inherited through an X-linked recessive pattern. In these cases, the gene responsible is located on the X chromosome, one of the sex chromosomes. Males (with one X chromosome) only need one altered copy of the gene to be affected. Females (with two X chromosomes) need a mutation in both copies of the gene, making them less likely to be affected. Therefore, X-linked recessive disorders are more common in males than females. Notably, fathers cannot pass X-linked traits to their sons.