What is Malan syndrome?
Malan syndrome is a rare genetic disorder caused by a change in the Nuclear Factor One X (NFIX) gene.
The NFIX gene is located on the short arm (called "p") of chromosome 19 at position 13.2.
This gene contains the instructions to produce NFIX protein.
Malan syndrome is associated with a loss of function in one of the two copies of the gene, referred to as NFIX haploinsufficiency. The one functioning copy of the gene does not produce enough NFIX protein for the body to function normally. The NFIX protein plays an essential role in brain and muscle development as well as skeletogenesis. Most often, NFIX variants are de novo, meaning they occur spontaneously for the first time in the affected individual with no prior family history.
The clinical features of Malan syndrome vary but may include:
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tall stature
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stereotypical craniofacial features, such as tall forehead, long or triangular face, deeply set eyes, down-slanting eyes, low set ears, small mouth that is often held open, thin upper lip, dental crowding
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intellectual disability- ranging from mild to severe
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macrocephaly (large head circumference)
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hypotonia (low muscle tone)
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vision impairment- strabismus, optic nerve atrophy, optic nerve hypoplasia, limited fields of vision, cortical visual impairment (CVI), lack of depth perception
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hearing impairment
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speech delay/inability to speak
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delayed gross and fine motor skills
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enlarged aorta- the main blood vessel that carries blood from the heart to the rest of the body
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structural abnormalities in the brain, such as enlarged ventricles and underdeveloped corpus callosum
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chiari malformation (brain tissue protrudes into spinal canal)
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seizures or EEG abnormalities
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skeletal anomalies, such as advanced bone age, scoliosis, sternum malformations
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joint hypermobility (increase in the range of movement of which a joint is capable)
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autistic-like traits
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behavioral challenges- anxiety and mood swings
A more detailed description of Malan syndrome can be found here in a recent publication (2018) including 45 newly diagnosed patients.
