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Massive diaphragmatic hernia and renal abnormalities in two unrelated families
144
HUMAN GENETICS SOCIETY OF AUSTRALASIA
Pathology (1980), 12, January
derived by Epstein Barr virus transformation of the collected cells and fresh and frozen preparations of B and T lymphocytes. The investigation of an HLA association with leprosy may provide insight into a genetic susceptibility to the disease, as well as the demonstration of the HLA-DR antigen distribution, in the population living in the coastal regions of Papua New Guinea. To explore the mode of transmission of the disease, approximately 20 families have been phenotyped for I2HLA-A, 2OHLA-B and 7HLA-DR antigen specificities. PRO6HYLACTlC INTERVENTION IN THREE UNUSUAL FAMILIES WITH DOMINANT INHERITANCE
ATHELHOCKEY King Edward Memorial Hospital, Perth, Western Australia Three kindreds are described with members affected by malignant melanoma, Down’s syndrome and congenital hydrocephalus respectively.Analysis of the pedigrees suggested Mendelian dominance, which was unusual for all 3 disorders. The consequent high risk for the children, or future offspring, justified an approach to other family members by means of a standardized letter in which prophylactic measures were outlined with an offer of genetic counselling. The letters were prepared and sent with the help of each index family. For the melanoma kindred avoidance of ultraviolet exposure and early consultation with regard to pigmented naevi was suggested. For the Down’s kindred amniocentesis was offered to any women intending children. The hydrocephalic family were advised that ultrasound monitoring in the latter part of pregnancy would enable the obstetrician to select the most suitable form of delivery for affected infants-i.e. Caesarean section. A number of members responded and sought counselling at the most appropriate Genetic Clinic. This genetic counselling gave opportunities for prevention in these families. MASSIVE DIAPHRAGMATIC HERNIA AND RENAL ABNORMALITIES IN TWO UNRELATED FAMILIES
JUDITH FORD Cytogenetics Department, Queen Elizabeth Hospital. Adelaide Two unrelated patients recently gave birth to male babies which were either stillborn or died soon after birth with massive diaphragmatic hernias. On autopsy, 2 babies from one woman (H.B.) showed polycystic kidneys, while the baby examined from the second woman (T.J.) showed unilateral renal agenesis. In addition, each of T.J.’s babies had a meningomyelocoele. Karyotypes from H.B., her husband, and her 2 stillborn children, showed no abnormality by Giemsa banding. Her family history,was consistent with an X-linked recessive gene, but no such gene has been previously described. Similar abnormalities have only been described in triploids, trisomy 18 and possible partial trisomy 16. Karyotypes were not performed on the babies of T.J., but T.J. herself shows a small extra band on the distal region of one X chromosome. The aetiology of this hand is uncertain, but it appears to he translocated from the distal region of the q arm of one chromosome 13 (band 13q33). Her normal daughters have been screened for this minute translocation and 2 of the 3 appear to carry it. Unilateral renal agenesis is a known X-linked gene. Whether the diaphragmatic hernia seen in both families might also be X-linked or whether it and gene(s) causing meningomyelocoele might be translocated from chromosome 13 (or elsewhere) will be discussed. THE TRlPLOlDY PHENOTYPE: A CONSEQUENCE OF PRIMARY PLACENTAL DISEASE?
D. M. 0.BECROFT& R. L. SHAW The Princess Mary Hospitalfor Children, Auckland, New Zealand Morphological studies have been performed on 5 triploid conceptuses, four 69,XXY born at 23 to 33 wk gestation and one 69,XXX born at about 20 wk gestation. Three mothers had toxaemia of pregnancy and there was inconstant identification of the additional features which may suggest the diagnosis pre-natally, i t . a large placenta and small foetus on scanning or high chorionic gonadotrophin and low oestriol excretions. Two infants were born alive, but survived less than 1 hr. All 5 were severely growth retarded while syndactyly, an adrenal cortical hypoplasia resembling that found in anencephaly, and minor cystic changes in kidneys were each found in at least 4 infants. Hypospadias of varying severity and undescended testes with Leydig cell hyperplasia were found in most 69,XXY’s. Severe cardiovascular or nervous system malformations were present less frequently and in 2 infants there were no malformations incompatible with prolonged survival. The unique association of neural tube defects with triploidy was confirmed in 2 infants with meningomyelocoeles and hydrocephalus. All 5 placentas were very large and showed the cystic changes and trophoblastic hyperplasia of partial hydatidiform moles. The hypothesis is advanced that the foetal phenotype of triploidy is largely or wholly secondary to the nutritional depletion or hormonal imbalance caused by the placental abnormalities.
HUMAN GENETICS SOCIETY OF AUSTRALASIA
Pathology (1980), 12, January
derived by Epstein Barr virus transformation of the collected cells and fresh and frozen preparations of B and T lymphocytes. The investigation of an HLA association with leprosy may provide insight into a genetic susceptibility to the disease, as well as the demonstration of the HLA-DR antigen distribution, in the population living in the coastal regions of Papua New Guinea. To explore the mode of transmission of the disease, approximately 20 families have been phenotyped for I2HLA-A, 2OHLA-B and 7HLA-DR antigen specificities. PRO6HYLACTlC INTERVENTION IN THREE UNUSUAL FAMILIES WITH DOMINANT INHERITANCE
ATHELHOCKEY King Edward Memorial Hospital, Perth, Western Australia Three kindreds are described with members affected by malignant melanoma, Down’s syndrome and congenital hydrocephalus respectively.Analysis of the pedigrees suggested Mendelian dominance, which was unusual for all 3 disorders. The consequent high risk for the children, or future offspring, justified an approach to other family members by means of a standardized letter in which prophylactic measures were outlined with an offer of genetic counselling. The letters were prepared and sent with the help of each index family. For the melanoma kindred avoidance of ultraviolet exposure and early consultation with regard to pigmented naevi was suggested. For the Down’s kindred amniocentesis was offered to any women intending children. The hydrocephalic family were advised that ultrasound monitoring in the latter part of pregnancy would enable the obstetrician to select the most suitable form of delivery for affected infants-i.e. Caesarean section. A number of members responded and sought counselling at the most appropriate Genetic Clinic. This genetic counselling gave opportunities for prevention in these families. MASSIVE DIAPHRAGMATIC HERNIA AND RENAL ABNORMALITIES IN TWO UNRELATED FAMILIES
JUDITH FORD Cytogenetics Department, Queen Elizabeth Hospital. Adelaide Two unrelated patients recently gave birth to male babies which were either stillborn or died soon after birth with massive diaphragmatic hernias. On autopsy, 2 babies from one woman (H.B.) showed polycystic kidneys, while the baby examined from the second woman (T.J.) showed unilateral renal agenesis. In addition, each of T.J.’s babies had a meningomyelocoele. Karyotypes from H.B., her husband, and her 2 stillborn children, showed no abnormality by Giemsa banding. Her family history,was consistent with an X-linked recessive gene, but no such gene has been previously described. Similar abnormalities have only been described in triploids, trisomy 18 and possible partial trisomy 16. Karyotypes were not performed on the babies of T.J., but T.J. herself shows a small extra band on the distal region of one X chromosome. The aetiology of this hand is uncertain, but it appears to he translocated from the distal region of the q arm of one chromosome 13 (band 13q33). Her normal daughters have been screened for this minute translocation and 2 of the 3 appear to carry it. Unilateral renal agenesis is a known X-linked gene. Whether the diaphragmatic hernia seen in both families might also be X-linked or whether it and gene(s) causing meningomyelocoele might be translocated from chromosome 13 (or elsewhere) will be discussed. THE TRlPLOlDY PHENOTYPE: A CONSEQUENCE OF PRIMARY PLACENTAL DISEASE?
D. M. 0.BECROFT& R. L. SHAW The Princess Mary Hospitalfor Children, Auckland, New Zealand Morphological studies have been performed on 5 triploid conceptuses, four 69,XXY born at 23 to 33 wk gestation and one 69,XXX born at about 20 wk gestation. Three mothers had toxaemia of pregnancy and there was inconstant identification of the additional features which may suggest the diagnosis pre-natally, i t . a large placenta and small foetus on scanning or high chorionic gonadotrophin and low oestriol excretions. Two infants were born alive, but survived less than 1 hr. All 5 were severely growth retarded while syndactyly, an adrenal cortical hypoplasia resembling that found in anencephaly, and minor cystic changes in kidneys were each found in at least 4 infants. Hypospadias of varying severity and undescended testes with Leydig cell hyperplasia were found in most 69,XXY’s. Severe cardiovascular or nervous system malformations were present less frequently and in 2 infants there were no malformations incompatible with prolonged survival. The unique association of neural tube defects with triploidy was confirmed in 2 infants with meningomyelocoeles and hydrocephalus. All 5 placentas were very large and showed the cystic changes and trophoblastic hyperplasia of partial hydatidiform moles. The hypothesis is advanced that the foetal phenotype of triploidy is largely or wholly secondary to the nutritional depletion or hormonal imbalance caused by the placental abnormalities.