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This congenital overgrowth syndrome is characterized by a triad of major features: macroglossia, pre- or postnatal gigantism ( 90th percentile), and anterior.
DNMT3A overgrowth syndrome is a disorder characterized by faster than normal growth before and after birth, subtle differences in facial features, and intellectual disability.Individuals with DNMT3A overgrowth syndrome are often longer than normal at birth and are taller than their peers throughout life. Many affected individuals become overweight in late childhood or adolescence. They may also have an abnormally large head size.The characteristic facial appearance of individuals with DNMT3A overgrowth syndrome includes; thick, horizontal eyebrows; and narrowed openings of the eyes (narrowed palpebral fissures).
Additionally, the upper front teeth are often larger than normal.Intellectual disability in DNMT3A overgrowth syndrome ranges from mild to severe. Individuals may have features of, which are characterized by impaired communication and socialization skills.Individuals with DNMT3A overgrowth syndrome may have other signs and symptoms, including a rounded upper back that also curves to the side , heart defects, flat feet , weak muscle tone (hypotonia), or joints that are loose and very flexible. Psychological disorders such as, anxiety, or can also occur in this disorder. As its name suggests, mutations in the gene cause DNMT3A overgrowth syndrome. The DNMT3A gene provides instructions for making an enzyme called DNA methyltransferase 3 alpha.
This enzyme is involved in DNA methylation, which is the addition of methyl groups, consisting of one carbon atom and three hydrogen atoms, to DNA molecules. DNA methylation is important in many cellular functions. These include regulating gene activity and certain chemical reactions and controlling the processing of chemicals that relay signals in the nervous system (neurotransmitters).
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DNA methyltransferase 3 alpha is particularly important for establishing DNA methylation patterns during development before birth.Some DNMT3A gene mutations that cause DNMT3A overgrowth syndrome lead to a decrease in normal enzyme function. As a result, there is a reduction in DNA methylation, particularly affecting DNA methylation before birth. It is unclear how other mutations affect protein function. Decreased DNA methylation likely disrupts the normal regulation of important developmental genes, although how these change cause the specific features of DNMT3A overgrowth syndrome is unknown.
Tatton-Brown K, Seal S, Ruark E, Harmer J, Ramsay E, Del Vecchio Duarte S, Zachariou A, Hanks S, O'Brien E, Aksglaede L, Baralle D, Dabir T, Gener B, Goudie D, Homfray T, Kumar A, Pilz DT, Selicorni A, Temple IK, Van Maldergem L, Yachelevich N; Childhood Overgrowth Consortium, van Montfort R, Rahman N. Mutations in the DNA methyltransferase gene DNMT3A cause an overgrowth syndrome with intellectual disability. 2014 Apr;46(4):385-8. Doi: 10.1038/ng.2917.
Epub 2014 Mar 9. Erratum in: Nat Genet. 2014 Jun;46(6):657.
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