X - linked Mental Retardation Hypotonic Facies Syndrome or Alpha - Thalassemia Mental Retardation Syndrome
Roger E Stevenson, MD, GENEClinics, October 15, 2007
 [for Professionals mainly]
ATRX Syndrome ...
Alpha Thalassemia / Mental RetardationX - linked mental retardation hypotonic facies ... ( XLMR - hypotonic facies ) syndrome is characterized by distinctive craniofacial features, genital anomalies, and severe developmental delays with hypotonia and mental retardation. Craniofacial abnormalities include small head circumference, telecanthus or ocular hypertelorism, small nose, tented upper lip, and prominent or everted lower lip with coarsening of the facial features over time. Although all patients have a normal 46,XY karyotype, genital anomalies range from hypospadias and undescended testicles to severe hypospadias and ambiguous genitalia to normal - appearing female genitalia. Global developmental delays are evident in infancy and some affected individuals never walk independently or develop significant speech.
Diagnosis/testing.
In an unknown percent of patients, hemoglobin H inclusions ( b - globin tetramers ) in erythrocytes can be demonstrated following incubation of fresh blood smears with 1% brilliant cresyl blue ( BCB ). Females who are unaffected carriers for X - linked mental retardation hypotonic facies syndrome have skewed X - chromosome inactivation, a finding which can be used with the family history information to help determine the carrier status of at-risk women. Molecular genetic testing of the XNP gene ( chromosomal locus Xq13.3 ) is available on a research basis only.
Clinical Diagnosis
X - linked mental retardation hypotonic facies syndrome may be suspected on the basis of craniofacial, genital, skeletal, and other somatic findings. Of greatest importance clinically is the failure to achieve developmental milestones on schedule. Cognitive function is usually profoundly retarded.
Most females who are unaffected carriers for X - linked mental retardation hypotonic facies syndrome have skewed X - chromosome inactivation ...
Clinical Description
Small head circumference, upsweep of the frontal hair, telecanthus or ocular hypertelorism, small triangular nose with retracted columella, tented upper lip, prominent or everted lower lip, and open mouth form a recognizable pattern of craniofacial findings. Irregular anatomy of the pinnae, wide spacing of the teeth, and tongue protrusion are supplemental findings, the latter two adding to a coarseness of the facial appearance, particularly after the first few years of life ...
Differential Diagnosis
Coffin - Lowry syndrome, an X - linked mental retardation syndrome caused by mutations in the RSK2 gene, may be confused with X - linked mental retardation hypotonic facies syndrome, especially in early childhood. Large fleshy hands and fingers, skeletal abnormalities, and absence of genital anomalies distinguish Coffin - Lowry syndrome. For information on laboratory testing for Coffin - Lowry syndrome ...
ATR - 16 is the association of alpha - thalassemia and MR in patients with a contiguous gene deletion involving the distal short arm of chromosome 16 ...
Alpha - thalassemia results from reduced production of the a chains of adult hemoglobin ... Patients with X - linked mental retardation hypotonic facies syndrome have a normal a - globin genotype ...
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Last Updated: 2008/1/07
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