SNP Shot: Genomic Insights

MN1 C-terminal truncation (MCTT) syndrome is a genetic disorder marked by intellectual disability, delays in development, distinctive facial characteristics, and abnormalities in the brain.

Most individuals with MCTT syndrome experience mild to moderate intellectual disability. Many are nonverbal or have very limited speech, sometimes using only one or two words or relying on sign language. Motor skill development is often delayed in childhood, with most children walking by age 2 or 3. However, they frequently require assistance with fine motor skills, like dressing themselves or using utensils.

Facial features often seen in individuals with MCTT syndrome include a sunken midface (midface hypoplasia), a high-arched palate, eyes that slant downward (downslanting palpebral fissures), widely spaced eyes (hypertelorism), shallow, bulging eyes (exophthalmos), a short, upturned nose, and small, low-set ears. Dental issues such as cone-shaped (conical), jagged, or crowded teeth are also sometimes present. In rare cases, premature fusion of skull bones (craniosynostosis) may occur.

Brain abnormalities are common in MCTT syndrome. The brain's surface normally has many folds, called gyri. A frequent finding is perisylvian polymicrogyria, where the perisylvian region has an excessive number of gyri that are irregular and unusually small. Atypical rhombencephalosynapsis, a malformation of the cerebellum (the brain area that coordinates movement), can also occur. This malformation involves tissue loss in the vermis (the central part of the cerebellum) and fusion of the two cerebellar hemispheres. These brain differences likely contribute to the motor difficulties and intellectual disability associated with MCTT syndrome.

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

Inheritance:

MCTT syndrome follows an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene in each cell is enough to cause the disorder. In most instances, the syndrome arises from new (de novo) mutations in the MN1 gene. These mutations occur either during the formation of egg or sperm cells in a parent or during early embryonic development. These cases typically occur in individuals with no family history of the disorder.