SUFU Gene

9q22.3 microdeletion is a chromosomal change in which a small piece of chromosome 9 is deleted in each cell. The deletion occurs on the long (q) arm of the chromosome in a region designated q22.3. This chromosomal change is associated with delayed development, intellectual disability, certain physical abnormalities, and the characteristic features of a genetic condition called Gorlin syndrome.

Many individuals with a 9q22.3 microdeletion have delayed development, particularly affecting the development of motor skills such as sitting, standing, and walking. In some people, the delays are temporary and improve in childhood. More severely affected individuals have permanent developmental disabilities along with intellectual impairment and learning problems. Rarely, seizures have been reported in people with a 9q22.3 microdeletion.

About 20 percent of people with a 9q22.3 microdeletion experience overgrowth (macrosomia), which results in increased height and weight compared to unaffected peers. The macrosomia often begins before birth and continues into childhood. Other physical changes that are sometimes associated with a 9q22.3 microdeletion include the premature fusion of certain bones in the skull (metopic craniosynostosis) and a buildup of fluid in the brain (hydrocephalus). Affected individuals can also have distinctive facial features such as a prominent forehead with vertical skin creases, upward- or downward-slanting eyes, a short nose, and a long space between the nose and upper lip (philtrum).

9q22.3 microdeletions also cause the characteristic features of Gorlin syndrome (also known as nevoid basal cell carcinoma syndrome). This genetic condition affects many areas of the body and increases the risk of developing various cancerous and noncancerous tumors. In people with Gorlin syndrome, the type of cancer diagnosed most often is basal cell carcinoma, which is the most common form of skin cancer. Most people with this condition also develop noncancerous (benign) tumors of the jaw, called keratocystic odontogenic tumors, which can cause facial swelling and tooth displacement. Other types of tumors that occur in some people with Gorlin syndrome include a form of childhood brain cancer called a medulloblastoma and a type of benign tumor called a fibroma that occurs in the heart or in a woman's ovaries. Other features of Gorlin syndrome include small depressions (pits) in the skin of the palms of the hands and soles of the feet; an unusually large head size (macrocephaly) with a prominent forehead; and skeletal abnormalities involving the spine, ribs, or skull.

MN1 C-terminal truncation (MCTT) syndrome is a condition characterized by intellectual disability, developmental delay, distinctive facial features, and brain abnormalities.

Most people with MCTT syndrome have mild to moderate intellectual disability. Many affected individuals are nonverbal, but some have speech limited to one or two words or communicate using sign language. Most children with this condition have delayed development of motor skills, such as crawling or walking, but are able to walk by age 2 or 3. However, they often need help with fine-motor skills, such as getting dressed or using a fork when eating.

Individuals with MCTT syndrome often have distinctive facial features that include a sunken appearance of the middle of the face (midface hypoplasia); a high arch in the roof of the mouth (high-arched palate); outside corners of the eyes that point downward (downslanting palpebral fissures); widely spaced eyes (hypertelorism ); shallow and bulging eyes (exophthalmos); a short, upturned nose; and small, low-set ears. Some affected individuals have dental abnormalities, such as cone-shaped (conical ), jagged, or crowded teeth. Rarely, people with MCTT syndrome have premature fusion of certain skull bones (craniosynostosis).

People with MCTT syndrome often have characteristic brain abnormalities. The surface of the brain normally has many ridges or folds, called gyri. A common brain abnormality in people with MCTT syndrome is called perisylvian polymicrogyria, in which an area of the brain called the perisylvian region develops too many gyri, and the folds are irregular and unusually small. Individuals with MCTT syndrome can also have a malformation of the part of the brain that coordinates movement (the cerebellum ). This malformation, called atypical rhombencephalosynapsis, is characterized by tissue loss in the central part of the cerebellum (known as the vermis) and fusion of the two sides of the cerebellum. These brain abnormalities likely contribute to the movement problems and intellectual disability that are common in MCTT syndrome. 

Less common features of MCTT syndrome include hearing loss, seizures, abnormal curvature of the spine, and heart abnormalities.