Alpha-Thalassemia/Mental Retardation Syndrome, X-Linked

Alternative Names

  • ATRX
  • Alpha-Thalassemia/Mental Retardation Syndrome, Nondeletion Type
  • ATR-X Syndrome
  • ATR, Nondeletion Type

Associated Genes

ATR-X Gene
Back to search Result
WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Other congenital malformations

OMIM Number

301040

Mode of Inheritance

X-linked recessive

Gene Map Locus

Xq21.1

Description

Alpha-Thalassemia/Mental Retardation Syndrome, X-Linked (ATRX) is a condition characterized by severe to profound mental retardation, distinctive craniofacial features, hypotonia, genital abnormalities, and hematological features of alpha thalassemia, in the absence of mutations in the alpha-globin gene complex.  The distinctive craniofacial features include microcephaly, telecanthus, a short triangular nose with flat nasal bridge and anteverted nostrils, mid face hypoplasia, tented vermilion of the upper lip, and thick or everted vermilion of the lower lip.  Genital abnormalities include hypospadias, micropenis, or ambiguous female external genitalia.  Most patients have mild to moderate anemia, secondary to alpha-thalassemia.  Interestingly, the alpha-thalassemia component is not present in all affected patients. 

Diagnosis is based on the clinical features.  Most patients tend to show the presence of HbH inclusion bodies in their erythrocytes.  However, this is not always the case.  Molecular genetic testing for mutations in the ATRX gene is the only confirmatory diagnostic test.  Management of the condition involves treating the symptoms.  Infants need to be put on calorie dense formula.  Excessive drooling can be managed by administration of anticholinergics or botulinum toxin type A injection of the salivary glands, or by surgery.  The anemia is mild and does not usually require treatment.  

Molecular Genetics

ATRX is transmitted in an X-linked recessive manner, through mutations in The ATRX gene.  Affected male patients either have a de novo mutation or have mothers who are asymptomatic carriers of the mutation.  The ATRX gene codes for a chromatin remodeler protein that functions as a histone chaperone complex, thus playing a major role in normal development.  

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
301040.1.1YemenMaleYesYes Global developmental delay; Delayed spe...NM_000489.6:c.5666T>GHemizygousAutosomal, RecessiveHamzeh et al. 2016
301040.1.2YemenMaleYesYes Global developmental delay; Delayed sp...NM_000489.6:c.5666T>GHemizygousAutosomal, RecessiveHamzeh et al. 2016 Sibling of 301040.1....
© CAGS 2024. All rights reserved.