ABSTRACT
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.
Subject(s)
Abnormalities, Multiple/genetics , Chromosome Inversion , Intellectual Disability/genetics , Sex Chromosome Aberrations/genetics , X Chromosome/ultrastructure , Dosage Compensation, Genetic , Fatal Outcome , Female , Humans , Infant, Newborn , Male , Multigene Family , Pedigree , Phenotype , Sex Chromosome Aberrations/pathology , X Chromosome/geneticsABSTRACT
Fragile-X and Sotos phenotypes may be difficult to distinguish. This is illustrated with a case report. Computer assisted phenotype analyses (MDDB), using the complete trait list of this patient, suggested the fragile-X diagnosis, which later was confirmed by molecular techniques. The results of corresponding phenotype analyses are summarized for 17 children with proven fragile-X, and 10 children with suggested Sotos syndrome.
Subject(s)
Fragile X Syndrome/genetics , Intellectual Disability/genetics , Muscle Hypotonia/genetics , Phenotype , Child , Databases, Bibliographic , Diagnosis, Computer-Assisted , Diagnosis, Differential , Fragile X Syndrome/diagnosis , Humans , Intellectual Disability/diagnosis , Male , Muscle Hypotonia/diagnosisABSTRACT
Clinical and pathological features of two siblings of opposite sex with the Pena-Shokeir phenotype are reported. A detailed account of the prenatal and dysmorphological findings is given in one case. A broad range of deformations regarded as secondary to fetal hypokinesia was present, including a number of yet unreported findings. One case showed additional endocrine hyperplasia and left lung trilobation. Both siblings displayed extensive, highly similar CNS-abnormalities. The type and convergence of these malformations differ from previously reported cases and characterize a new familial subtype of the Pena-Shokeir phenotype.
