Alpha-thalassemia mental retardation syndrome (ATRX), also called alpha-thalassemia X-linked intellectual disability syndrome, nondeletion type or ATR-X syndrome, is an X-linked recessive condition associated with a mutation in the ATRX gene. Males with this condition tend to be moderately intellectually disabled and have physical characteristics including coarse facial features, microcephaly (small head size), hypertelorism (widely spaced eyes), a depressed nasal bridge, a tented upper lip and an everted lower lip. Mild or moderate anemia, associated with alpha-thalassemia, is part of the condition. Females with this mutated gene have no specific signs or features, but if they do, they may demonstrate skewed X chromosome inactivation. Atr-X Syndrome can also come with problems regulating Levels and normal bodily temperature regulation, the cause of this is widely debated but currently unknown, many children with Atr-X may need oxygen support long term through their entire life but cases that require long term oxygen are rare, however many children with Atr-x will require help with feeding such and NG/NJ tube feeding, this is not present in all cases however. Many children will also experience severe reflux issues and may require regular medical suction procedures. Epigenetics "The role of ATRX as a regulator of heterochromatin dynamics raises the possibility that mutations in ATRX may lead to downstream transcriptional effects across the complex of genes or repetitive regions involved in the global context of the disorder, in addition to explaining phenotypical differences in these patients. For example, ATRX mutations affect the expression of alpha-globin gene cluster, causing alpha-thalassemia." ATRX interacts with the transcription co-factor DAXX and the alpha-globin gene cluster. Together they are all responsible for depositing the histone H3.3 at telomeric and pericentromeric regions. They are also responsible for regulating gene expression at these regions. ATRX is characterized by hypo- and hypermethylated regions. It's important to recognize that having a mutation in the ATRX gene does not necessarily guarantee that the patient has ATR-X syndrome. However, it is common within ATR-X patients to have global hypermethylation of usually unmethylated regions, like CpG islands and promoters. Several of the genes that undergo methylation changes are responsible for biosynthetic, metabolic, and methylation processes, and 42.5% of these genes are present in the telomeric and pericentromeric regions. A couple of these genes include: PRDM9 and 2-BHMT2. PRDM9 encodes for a histone H3 lysine-4 trimethyltransferase, which is a known target for ATRX, and 2-BHMT2 encodes for betaine-homocysteine methyltransferase, which catalyzes the