Hemizygous deletion of 3p25-pter is associated with a phenotype of profound growth failure, microcephaly, characteristic facial changes, and mental retardation. Since the severity may be quite variable, we have studied 3 cases of del 3p25-pter to define the clinical manifestations and the critical chromosome region for phenotypic expression. The patient we now report died at age 6 months and provided an opportunity for a detailed necropsy analysis for only the second time in a del(3p) patient. He had marked hypoplasia of all organs, hypomyelination of white matter, and multiple renal cortical microcysts. Ordered genomic markers from the distal regions of chromosome 3p aided in determining the parent of origin of each deletion and in defining the boundaries of the deleted chromosomal segments. The deleted markers distal to the RAF1 oncogene in 2 of the 3 patients were consistently hemizygous. One patient had an interstitial deletion based on evidence of diploid inheritance of one of the most distal loci (D3S17). Available genetic linkage maps suggest that the deletion spans at least 19 centimorgans (cM).

American Journal of Medical GeneticsVolume 41, Issue 3 p. 390-390 Letter to the Editor Reply to Dr. Rivera Dr. Jeanette C. Ramer, Corresponding Author Dr. Jeanette C. Ramer Penn State College of Medicine, University Hospital, Hershey, PA 17033Department of Pediatrics, The Milton S. Hershey Medical Center, Penn State College of Medicine, P.O. Box 850, Hershey, PA 17033Search for more papers by this authorDavid B. Robins, David B. Robins Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorJavad Todighi, Javad Todighi Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorPhilip N. Mowrey, Philip N. Mowrey Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorSaverio Ligato, Saverio Ligato Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorRoger L. Ladda, Roger L. Ladda Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this author Dr. Jeanette C. Ramer, Corresponding Author Dr. Jeanette C. Ramer Penn State College of Medicine, University Hospital, Hershey, PA 17033Department of Pediatrics, The Milton S. Hershey Medical Center, Penn State College of Medicine, P.O. Box 850, Hershey, PA 17033Search for more papers by this authorDavid B. Robins, David B. Robins Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorJavad Todighi, Javad Todighi Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorPhilip N. Mowrey, Philip N. Mowrey Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorSaverio Ligato, Saverio Ligato Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorRoger L. Ladda, Roger L. Ladda Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this author First published: 1 December 1991 https://doi.org/10.1002/ajmg.1320410324AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume41, Issue31 December 1991Pages 390-390 RelatedInformation

Neuropathologic examination of two siblings with phenotypic features consistent with Marden-Walker syndrome revealed central nervous system abnormalities which include reduction in the number of spinal anterior horn cells. The occurrence of these changes in a sibling pair provides strong evidence for a genetic etiology. The relationship between the neuropathologic changes and other phenotypic manifestations in this syndrome and in the closely related syndrome of Pena-Shokeir are discussed.

Five matings to a dir ins (6;2)(q16;q31q33) carrier have produced a high frequency (42%) of offspring with unbalanced karyotypes. Five children have the derivative chromosome 2 resulting in del (2)(q31q33) and one individual received the derivative chromosome 6 leading to dup (2)(q31q33). The findings associated with the deletion include pre- and postnatal growth retardation, developmental delay, minor facial anomalies, seizures, complex structural heart defects, and limb deficiency. Autopsy of one individual showed complex brain malformations including hydrocephalus secondary to obstruction of the foramina of Monro, extensive heterotopias and polymicrogyria, and an unusual form of total anomalous pulmonary venous return. We compare the findings in these children to those of previously reported cases and construct an overview of the range of anomalies. Apparently, no other individual with dup (2)(q31q33) has been described. We compare the physical peculiarities of our patient with those of individuals with duplications of overlapping regions of 2q.

We describe 2 sibs with Roberts-SC phocomelia syndrome. Although an ultrasound scan performed at 13 weeks of gestation failed to identify specific abnormalities, repeat scan at 17 weeks detected tetraphocomelia. Ultrasonography can reliably detect Roberts-SC phocomelia prenatally; however, serial scans may be needed. Postmortem examination of the proposita confirmed the sonographic findings and also disclosed dysplastic kidneys and ovarian dysgenesis. The degree of phenotypic variation observed between the sibs supports the hypothesis that Roberts syndrome and SC phocomelia represent a single genetic entity.