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Alpha-thalassemia x-linked intellectual disability syndrome

XLMR hypotonic face syndrome, ATR-X syndrome, Alpha thalassemia mental retardation syndrome, nondeletion type, X-linked, X-linked alpha thalassemia mental retardation syndrome (ATR-X), ATR, nondeletion type

Overview

Alpha thalassemia X-linked intellectual disability syndrome is an inherited disorder that affects many parts of the body. This condition occurs almost exclusively in males.

Males with alpha thalassemia X-linked intellectual disability syndrome have intellectual disability and delayed development. Their speech is significantly delayed, and most never speak or sign more than a few words. Most affected children have weak muscle tone (hypotonia), which delays motor skills such as sitting, standing, and walking. Some people with this disorder are never able to walk independently.
Almost everyone with alpha thalassemia X-linked intellectual disability syndrome has distinctive facial features, including widely spaced eyes, a small nose with upturned nostrils, and low-set ears. The upper lip is shaped like an upside-down "V," and the lower lip tends to be prominent. These facial characteristics are most apparent in early childhood. Over time, the facial features become coarser, including a flatter face with a shortened nose.

Most affected individuals have mild signs of a blood disorder called alpha thalassemia. This disorder reduces the production of hemoglobin, which is the protein in red blood cells that carries oxygen to cells throughout the body. A reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Rarely, affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, and fatigue.

Additional features of alpha thalassemia X-linked intellectual disability syndrome include an unusually small head size (microcephaly), short stature, and skeletal abnormalities. Many affected individuals have problems with the digestive system, such as a backflow of stomach acids into the esophagus (gastroesophageal reflux) and chronic constipation. Genital abnormalities are also common; affected males may have undescended testes and the opening of the urethra on the underside of the penis (hypospadias). In more severe cases, the external genitalia do not look clearly male or female (ambiguous genitalia).

Symptoms - Alpha-thalassemia x-linked intellectual disability syndrome

  • Intellectual disability
  • Muscle weakness (hypotonia)
  • Short height, particular facial appearance
  • Genital abnormalities
  • Abnormality of the fontanelles or cranial sutures
  • Cognitive impairment
  • Cryptorchidism
  • Hypertelorism
  • Malar flattening
  • Male pseudohermaphroditism
  • Microcephaly
  • Neurological speech impairment
  • Facial anomalies
  • Hemoglobinosis
  • Widely spaced eyes
  • Mental retardation
  • Small head

Causes - Alpha-thalassemia x-linked intellectual disability syndrome

Alpha thalassemia X-linked intellectual disability syndrome results from mutations in the ATRX gene and is inherited in an x-linked way. This gene provides instructions for making a protein that plays an essential role in normal development. Although the exact function of the ATRX protein is unknown, studies suggest that it helps regulate the activity (expression) of other genes. Among these genes are HBA1 and HBA2, which are necessary for normal hemoglobin production.

This condition is inherited in an X-linked recessive pattern. The ATRX gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), one working copy of the ATRX gene can usually compensate for the mutated copy. Therefore, females who carry a single mutated ATRX gene almost never have signs of alpha thalassemia X-linked intellectual disability syndrome. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Prevention - Alpha-thalassemia x-linked intellectual disability syndrome

Not supplied.

Diagnosis - Alpha-thalassemia x-linked intellectual disability syndrome

The red blood cells of someone affected by ATR-X syndrome have a tell-tale appearance under the microscope which allows the diagnosis of ATR-X to be confirmed by a simple blood test.

Prognosis - Alpha-thalassemia x-linked intellectual disability syndrome

Not supplied.

Treatment - Alpha-thalassemia x-linked intellectual disability syndrome

Treatment includes regular visits to the doctor to monitor growth and intellectual development, early intervention and special education programs, and special formula to help with feeding and nutrition.

Resources - Alpha-thalassemia x-linked intellectual disability syndrome

  • NIH
  • Genetics Home Reference
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