MBD5-associated neurodevelopmental disorder; 2q23.1 microdeletion syndrome - MBD5 gene and chromosome 2

The neurodevelopmental disorder related to MBD5 (MAND), also known as the 2q23.1 microdeletion syndrome, is a condition that affects neurological and physical development.

The usual characteristics of this process include mild to severe intellectual disability and developmental delay; epilepsy; feeding problems due to hypotonia; sleep problems like nightmares, waking up often during the night and waking up early in the morning; behavioral problems similar to autistic spectrum disorder; stereotypies, such as clapping, licking hands and sucking on hands; and teeth grinding. In addition, in individuals with this disease, some subtle facial features are common, including a broad forehead, thick and very arched eyebrows, anomalies of the outer ear, a short nose, a wide or depressed nasal bridge, and corners of the mouth tilted downward. Some affected individuals have mild skeletal abnormalities, such as small hands and feet, brachydactyly, clinodactyly of the fifth finger, or a wide space between the first and second fingers (known as sandal space). Rarely, people with MAND have heart abnormalities.

This process is due to mutations in the MBD5 (methyl-CpG binding domain protein 5) gene, located on the long arm of chromosome 2 (2q23.1), which belongs to the gene family of the methyl-CpG binding domain (MBD). The MBD5 protein is probably involved in the regulation of gene expression and the control of the synthesis of proteins that are involved in neurological functions such as learning, memory and behavior. The MBD5 protein also seems to play a role in the growth, proliferation and differentiation of several cell types.

Some of the identified mutations of the MBD5 gene that cause MAND eliminate large segments of the MBD5 gene or result in the synthesis of a non-functional altered protein. These mutations affect a copy of the gene in each cell. As a result, there is less MBD5 protein available to regulate the expression of certain genes, leading to the synthesis of uncontrolled proteins. Proteins that play a role in neurological functions are particularly affected. Besides, an additional copy of the MBD5 gene or a loss of the complete gene in each cell can lead to the development of MAND. In these cases, MAND is due to a duplication or deletion of a small part of the long arm of chromosome 2 at position 2q23.1. The duplicated or deleted segments may vary in size, but always include the MBD5 gene and, often, additional genes.

This process is considered an autosomal dominant disease because an altered copy of chromosome 2 or the MBD5 gene in each cell is sufficient to express the process. The majority of MAND cases occur in people with no history of the disease in their family as random events during the formation of reproductive cells. In a small percentage of cases, people with MAND inherit the chromosome or altered gene from a parent with the disease.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with the neurodevelopmental alteration related to MBD5 (MAND), by means of complete PCR amplification of the exons of the MBD5 gene, and their subsequent sequencing.

Recommended samples: blood drawn with EDTA for separation of blood leukocytes, or card impregnated with dried blood sample (IVAMI can mail the card to deposit the blood sample).