Two brothers with multiple congenital anomalies and mental retardation due to disomy (X)(q12->q13.3) inherited from the mother

We present the phenotypic, cytogenetic and molecular findings in two dysmorphic and mentally retarded brothers with disomy Xq12-->q13.3. The mother and the grandmother carry the same rearrangement of the X chromosome, which was interpreted as an inverted insertion of the segment (X)(q12-->q13.3) into Xq21.2. The X-inactivation-specific-transcript (XIST) is expressed in the probands' mother but is absent in her son, confirming the hypothesis that X inactivation is realized only if two X inactivation centers reside on different X-chromosomes (trans-configuration). In the phenotypically normal mother the aberrant X chromosome was late replicating in all cells, indicating functional monosomy of the constitutional segment trisomy. The phenotype of the brothers is considered to be the consequence of a functional disomy Xq12-->q13.3. The trait combination observed in the brothers was compared with the spectrum of clinical and anthropological traits for proximal Xq disomy in males, elaborated by phenotype analyses of the available literature cases.