SNP Shot: Genomic Insights

MBD5-associated neurodevelopmental disorder (MAND) is a condition impacting both brain and physical development.

MAND commonly causes intellectual disability and developmental delays, ranging from mild to severe. Affected children often struggle with coordination, typically beginning to walk later than expected, around age 2 or 3. Their gait is frequently characterized by unsteadiness and a wide stance. Speech production and comprehension are significantly limited. Epilepsy, marked by recurring seizures, usually develops by age 2. Many children with MAND experience feeding difficulties due to low muscle tone (hypotonia) and are also prone to constipation.

Sleep disturbances are frequently observed in individuals with MAND, including night terrors, frequent awakenings, and early morning rising. Consequently, daytime fatigue is common due to insufficient and poor-quality sleep. Many individuals with MAND exhibit traits reminiscent of autism spectrum disorder, a developmental condition affecting communication and social interaction. These traits may include a short attention span, repetitive hand movements (stereotypies) such as clapping, hand licking, and hand sucking, and teeth grinding.

Individuals with MAND may display subtle facial characteristics, such as a broad forehead, thick and arched eyebrows, ear abnormalities, a short nose, a wide or flattened nasal bridge, downturned mouth corners, a protruding upper lip (tented lip), and a full lower lip. Some individuals also present with minor skeletal abnormalities, including small hands and feet, short fingers (brachydactyly), curved pinky fingers (fifth-finger clinodactyly), or a wide space between the big toe and second toe (sandal gap). Heart abnormalities are infrequent.

Inheritance:

MAND is classified as an autosomal dominant disorder. This means that only one altered copy of chromosome 2 or the MBD5 gene within each cell is enough to trigger the condition. In most instances, MAND is not inherited but arises from spontaneous mutations during the formation of egg or sperm cells in one of the parents. These instances occur in families with no previous history of MAND. In a small number of cases, individuals with MAND inherit the altered chromosome or gene from an affected parent.