ATR-X Syndrome

ATR-X is an acronym for alpha-thalassemia, mental retardation, X-linked syndrome. It is characterized by genital abnormalities, microcephaly, midface hypoplasia, severe mental retardation, neuromotor dysfunction, seizures, and hypotonia. Occasionally, the patient presents with a ventricular septal defect and gastrointestinal reflux.

X-Linked Mental Retardation Hypotonic Face Syndrome; XLMR Hypotonic Face Syndrome.

Caused by mutations of the ATR-X gene. It is inherited as an X-linked dominant transmission, and only males are affected. α-Thalassemia/mental retardation syndrome also has been suggested to be a contiguous gene syndrome resulting from deletion in 16p.

There are four subtypes of α-thalassemia. In the presence of a defect on the one α-globin gene, the patient presents with no symptoms of anemia and requires no treatment. The patient is known as a silent carrier. If two α-globin genes are missing or damaged, the condition is known as α-thalassemia minor or α-thalassemia trait. In the case of three missing α-globin genes, the person has mild-to-moderately severe anemia, and this condition is termed hemoglobin H disease because it causes production of a heavy hemoglobin that is less stable than normal hemoglobin. The mild forms may not require any treatment. The more severe forms usually do not require treatment with blood transfusions except during periods of stress on the body (such as infection). If all four α-globin genes are missing, the child will die before birth. This hemoglobin sometimes is called hemoglobin Bart.

X-linked inherited recessive disorder resulting from a defect in the gene encoding X-linked helicase-2. The helicases are involved in numerous intracellular functions, including DNA recombination and regulation of transcription. It also has been suggested to result from a deletion in the 16p gene.

Patients affected with this disorder present with significant postnatal growth deficiency and mental retardation with absent speech capability. The clinical characteristics describing this entity are numerous and include microcephaly, midface hypoplasia, low-set ears that are rotated posteriorly, low nasal bridge, carp-shaped mouth, full lips, and large protruding tongue. The cardiovascular system is most often affected with a perimembranous ventricular septal defect. The shape of the chest is abnormal because ribs are frequently missing. Most patients have hernias and gastroesophageal reflux. The genitourinary system shows hypospadias, small penis, shawl scrotum, cryptorchidism. Renal function demonstrates hydronephrosis and renal agenesis. Neurologically, besides severe mental retardation, spasticity and seizures activity resulting from cerebral atrophy are the most frequent features. Defects of the musculoskeletal system show kyphoscoliosis resulting from hemivertebrae, coxa valga of the pelvis, tapering fingers, fifth finger clinodactyly, and a talipes equinovarus prominent in the feet. The hematology system shows mild hypochromic microcytic anemia and a mild form of hemoglobin H disease. The disease presents with all hematologic characteristics of an α-thalassemia disease.

Complete hematologic evaluation must be obtained before surgery. The hematocrit should be checked because of the high incidence of anemia. The cardiovascular system should be assessed and an echocardiogram obtained. ...