Malan syndrome is caused by genetic changes (specifically, pathogenic variants) in the NFIX gene.
Understanding Malan Syndrome and Its Genetic Basis
Malan syndrome, also known as Sotos syndrome 2, is a rare genetic disorder typically presenting in infancy. The root cause lies within the NFIX gene, which plays a critical role in development.
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The NFIX Gene: This gene provides instructions for making a protein called nuclear factor I X. This protein is a transcription factor, meaning it controls the activity of other genes, particularly those involved in brain development and skeletal growth.
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Pathogenic Variants (Mutations): Changes (mutations or pathogenic variants) within the NFIX gene disrupt the normal function of the NFIX protein. This disruption in gene regulation then leads to the various features associated with Malan syndrome.
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How the Mutation Occurs: The NFIX gene variant can be inherited from a parent who carries the altered gene or, more frequently, can occur as a de novo (new) mutation in the affected individual. De novo mutations are not inherited and occur randomly during the formation of egg or sperm cells or during early embryonic development.
Common Features of Malan Syndrome Resulting from NFIX Mutations
Although the severity and specific symptoms can vary, common features associated with Malan Syndrome, stemming from the NFIX mutation, include:
- Intellectual disability: Ranging from mild to moderate.
- Overgrowth: Characterized by increased height and/or head circumference (macrocephaly) during childhood. However, growth may normalize in adulthood.
- Distinctive facial features: Including a prominent forehead, long face, and pointed chin.
- Skeletal abnormalities: Possible findings can include scoliosis, joint hypermobility, and/or foot abnormalities.
- Other potential issues: Seizures, cardiac anomalies, and behavioral problems can also occur.
Diagnosis and Genetic Testing
Diagnosis often involves clinical evaluation of the characteristic features of Malan syndrome. However, confirmation requires genetic testing, specifically sequencing of the NFIX gene, to identify the presence of a pathogenic variant.
