SNP Shot: Genomic Insights

Mabry syndrome is a genetic disorder characterized by a combination of features, including intellectual disability, characteristic facial appearances, elevated levels of alkaline phosphatase in the blood (hyperphosphatasia), and other potential health issues.

Individuals with Mabry syndrome often experience moderate to severe intellectual disability. Speech development is typically limited or absent, and they may be delayed in achieving motor milestones such as sitting, crawling, and walking. Hypotonia (low muscle tone) is common, and many develop epilepsy (recurrent seizures) during early childhood. These seizures are generally generalized tonic-clonic seizures, involving muscle stiffness, convulsions, and loss of consciousness.

Distinctive facial features are observed in individuals with Mabry syndrome, including widely spaced eyes (hypertelorism), elongated eyelid openings (long palpebral fissures), a nose with a wide bridge and rounded tip, downturned corners of the mouth, and a thin upper lip. It's important to note that these facial characteristics tend to become less prominent as individuals age.

Hyperphosphatasia, an increase in alkaline phosphatase levels in the blood, is present from the first year of life in individuals with Mabry syndrome. The specific type of alkaline phosphatase elevated in Mabry syndrome is the tissue non-specific type, found throughout the body. Affected individuals typically exhibit alkaline phosphatase levels one to two times higher than normal, although levels can be up to 20 times higher in some cases. These elevated levels tend to remain stable throughout life. While hyperphosphatasia itself doesn't appear to cause any health problems, its presence can aid in the diagnosis of Mabry syndrome.

Another common finding in Mabry syndrome is brachytelephalangy, characterized by shortened bones at the tips of the fingers, which can be detected through x-ray imaging. Nail hypoplasia, or underdeveloped fingernails, may also occur. Some individuals with Mabry syndrome may exhibit digestive system abnormalities, such as anal stenosis or anal atresia (narrowing or blockage of the anus), or Hirschsprung disease (a condition causing severe constipation or intestinal blockage). In rare cases, hearing loss can also be present.

The signs and symptoms of Mabry syndrome can vary significantly from person to person. Some individuals may only experience intellectual disability and hyperphosphatasia, without the characteristic facial features or other health problems associated with the syndrome.

Inheritance:

Mabry syndrome follows an autosomal recessive inheritance pattern. This means that for an individual to be affected, they must inherit a mutated copy of the responsible gene from each parent. The parents, while carrying one copy of the mutated gene, typically do not exhibit any signs or symptoms of the condition themselves.