Maternal uniparental disomy 7 - review and further delineation of the phenotype

Uniparental disomy (UPD) is defined as the inheritance of both homologous c hromosomes from only one parent. So far, maternal UPD 7 has been described in 28 cases. Here, we report 4 new cases, present clinical information of 5 cases previously reported by us, and review the clinical and molecular fin dings of all 32 cases. We found a phenotype characterized by pre- and postn atal growth retardation, occipitofrontal head circumference in the lower no rmal range, a triangular face, and retarded bone maturation. Findings of th e facial gestalt included a high and broad forehead and a pointed chin. A b road mouth with down-turned corners, prominent ears, cafe-au-lait spots, he mihypotrophy, or clinodactyly were rarely present. Psychomotor development was delayed in 6 cases. The clinical findings strikingly resemble the pheno type of the heterogeneous Silver-Russell syndrome (SRS). Other anomalies we re less frequently found than in SRS. Molecular investigations revealed 11 cases with isodisomy and 17 cases with heterodisomy. In 4 cases this inform ation was not available. From the allelic distribution of the microsatellit es investigated, 9 cases might be the consequence of an error at maternal m eiosis I, and 6 cases might be due to non-disjunction at maternal meiosis I I. Three of the 17 heterodisomic cases had trisomy 7 in chorionic villi, in the remaining cases no prenatal diagnosis through chorionic villus samplin g was reported. Conclusion Maternal UPD 7 should be investigated in children with pre- and postnatal growth retardation and a facial gestalt characterized by a high a nd broad forehead and a pointed chin, as well as in confined placental mosa icism for trisomy 7.