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Saethre-chotzen syndrome and its relationship to other craniosynostoses
1 12 HUMAN GENETICS SOCIETY OF AUSTRALASIA (pl lq13). appear from the literature to be repeatable. The inv(l8) was detected through a recombinant index case, 46,XY,rec( 18), dup q. inv( 18) (pllq12) pat. A second recombinant index case was a spontaneouslyaborted product of conception, 46,XX,rec(2), dup p, inv(2) (p15q37 or p13q35) mat. A possible inversion, inv(4) (p14q12), was found in a normal mother and her mentally retarded son. This rearrangement is difficult to distinguish from an insertion, ins(4) (q12p12p14). The implication of the difficulty of distinction between possible inversion or insertion is illustrated by comparison of a paracentric inv(5) (q22q31) pat in an amniocentesis sample with an ins(5) (p1403p1500p1505) ascertained through the recombinant 46,XX,rec(5), dup p, ins(5) (p1403pl500pl505) mat. FLUORODEOXYURIDINE SYNCHRONIZATION OF BONE MARROW CHROMOSOMES LORNA M. WEBBER& 0. MARGARETGARSON Cytogenetic Unit,
Uiniwrsity oJ”Melbourne, Deparlment of Medicine, St Vincent’s Hospital, Melbourne, Australia 4 method for synchronization of bone marrow cells and stimulated lymphocytes with fluorodeoxyuridine (FdU) is presented and compared with methotrexate (MTX) synchronization. FdU has the advantage of not requiring cell washing for release of the DNA synthesis block and was found to be more beneficial for bone marrow cultures because it generally produced a higher mitotic yield and was less damaging to chromosomes. Late replication banding, produced after releasing the FdU block with bromodeoxyuridine (BrdU). indicated that cells in midsynthesis at the time of the block release were those that showed the most increase in chromosome length and the most improvement in the quality of the metaphase spread. Therefore, because bone marrow cells have a longer cell cycle time than stimulated lymphocytes, a minimum of 7-8 h culture after release of the block is recommended to give optimum results. It was also found that to increase the yield of mitoses, at least 6-8 h of growth is necessary before the addition of either of these synchronizing agents.
Pathology (1983), 15, January favourably to the use of visual aids and stated a preference for early referral to genetic counsellors. Of 72% of consultands who were satisfied with genetic counselling, 25% said that they would appreciate a followup appointment. SAETHRE-CHOTZEN SYNDROME AND ITS RELATIONSHIP TO OTHER CRANIOSYNOSTOSES J. WHITE, L. J. SHEFFIELD,D. A. SIMPSON& D. J. DAVID South
Australian Cranio Facial Unit Saethre Chotzen Syndrome is a dominantly inherited syndrome with variable ‘features including craniosynostosis, facial asymmetry, low set frontal hairline, ptosis and soft tissue syndactyly. Review of 7 cases of the syndrome referred to the South Australian Cranio Facial Unit showed a positive family history in all but 2 cases. There was wide variability of expression both between and within families. Craniosynostosis was present in 5 cases. all of which had at least coronal synostosis. Facial asymmetry was present in 6 cases, and syndactyly was minimal if present. Ptosis, malocclusions and nasal septa1 deviation were common features. Several other cases with craniosynostosis caused diagnostic problems, as there appears to be some overlap between Saethre Chotzen Syndrome, Crouzon Syndrome and Craniofrontonasal Dysplasia. Early diagnosis, combined with genetic counselling and craniofacial surgery should minimize the eventual deformity and long term effects on the family. A DEFECT IN COBALAMIN (VITAMIN 812) METABOLISM ASSOCIATED WITH HOMOCYSTINURIA AND METHYLMALONIC AClDURlA BRIDGETWILCKEN.JUDITH HAMMOND& MARTIN SILINK Oliver Latham Laboratory. North Ryde & Royal Alexandra Hospital for
Children, Sydney
University of Melbourne, Department of Medicine, St Vincent’s Hospital, Melbourne If BrdU is incorporated into DNA during the latter stages of DNA synthesis, late replication banding patterns can be produced by exposure to light followed by incubation in a hot salt solution. This produces BrdU late replication R bands after staining in Giemsa. We have found that no pretreatment of the slides is necessary to produce banding if an alkaline phosphate buffered Giemsa solution is used for staining. However. this produces a reverse form of differentiation which results in late replication G-banding. We have found this technique very useful because ( I ) no pretreatment is required and the banding patterns are very clear; (2) slides can be differentiated immediately and even 12 mth old slides can be satisfactorily differentiated; (3) slides cannot be overtreated, therefore this is a useful procedure when only a few preparations are available for banding; and (4) slides may be sequentially stained R G or G C. The poster describes and illustrates this banding technique.
A girl aged 10% yr had suffered lethargy and intellectual deterioration for 6 mth. Urinary metabolic screening revealed homocystinuria and methylmalonic aciduria. The hemoglobin level was 12 d d l , the bone marrow showed megaloblastic changes, but serum levels of B,*, folate and transcobalamins I and I1 were normal. Genetic complementation studies on a cell line cultured from skin fibroblasts revealed a defect in cobalamin metabolism of the Cbl C class. In man only 2 reactions require a coenzyme form of vitamin B,2: the remethylation of homocysteine to methionine requires methyl cobalamin, and the formation of succinyl CoA from L methylmalonlyl CoA requires adenosyl cobalamin. Of the 6 published cases of homocystinuria with methylmalonic aciduria due to an inborn error of cobalamin metabolism, four have been assigned to the complementation group ‘Cbl C‘. Two patients died in infancy, despite B,, therapy, one died aged 7 yr, and one presented with lethargy and delayed development at 18 mth, but is well aged 12 yr with B,* therapy. All 3 patients who came to autopsy showed atherosclerotic lesions in small arteries. Our patient appears to have a mild form of the Cbl C defect of cobalamin metabolism. On treatment with I.M. cyanocobalamin her plasma homocystine level and urinary methylmalonic acid excretion decreased but remained abnormal, her lethargy vanished and her mental and physical progress is normal after one yr. The long term outlook must remain uncertain, particularly in relation to atherosclerosis.
A FOLLOW-UP EVALUATION OF A GENETIC COUNSELLING SERVICE P. WHITE & L. J. SHEFFIELD Adelaide Children’s Hospital and
CYSTIC FIBROSIS SCREENING OF 41 000 NEONATES, USING A DRIED BLOOD SPOT IMMUNO-REACTIVE TRYPSIN ASSAY BRIDGETWILCKEN,RUTH URWIN,A. R. D. BROWN& D. A. BROWN
SEQUENTIAL LATE REPLICATION R AND G BANDING PAlTERNS
LORNA M. WEBBER& 0. MARGARETGARSON Cytogenetic Unit,
Flinders University Medical School Fifty individuals or families who have received genetic counselling over a 7 mth period were personally interviewed for a follow-up study of the genetic counselling service. The interview took place 12-19 mth after counselling. 86% of those interviewed had some understanding of their condition and 48% claimed that genetic counselling had directly increased their ability to cope. This understanding was shown to be promoted by the sending of a letter summarizing the contents of the genetic counselling session. 64% had a good recall of the risk figure quoted and in 73% of those interviewed the consultand‘s perception of whether the risk was high or low was identical to the genetic counsellors as recorded in the genetic records. This perception of risk had little effect on the couples’ attitude to having more children whilst it seemed that the perceived burden was more important. The consultands generally reacted
Oliver Latharn Laboralorv, N.S. W. Health Commission
A reliable screening test for cystic fibrosis (CF) has long been sought. Recently Crossley, Elliott & Smith showed elevated blood immunoreactive trypsin (IRT) levels in neonates with CF, and developed a radioimmunoassay for IRT in dried blood spots. In N.S.W. we used Crossley’s reagents and a modified method to screen 41 000 babies. IRT was elevated in 237, and 203 repeat blood samples have so far been received. Twenty-one babies had persistently elevated IRT. and CF was confirmed in all by sweat testing. Of the 21 CF babies, 6 had meconium ileus and 3 had a sibling with CF, but in 12 the diagnosis was unsuspected. Three C F babies had normal stool trypsin, suggesting that the test will identify patients with adequate pancreatic function. No missed cases are yet known. In retrospective studies of blood spot samples from 36 newborns later
Uiniwrsity oJ”Melbourne, Deparlment of Medicine, St Vincent’s Hospital, Melbourne, Australia 4 method for synchronization of bone marrow cells and stimulated lymphocytes with fluorodeoxyuridine (FdU) is presented and compared with methotrexate (MTX) synchronization. FdU has the advantage of not requiring cell washing for release of the DNA synthesis block and was found to be more beneficial for bone marrow cultures because it generally produced a higher mitotic yield and was less damaging to chromosomes. Late replication banding, produced after releasing the FdU block with bromodeoxyuridine (BrdU). indicated that cells in midsynthesis at the time of the block release were those that showed the most increase in chromosome length and the most improvement in the quality of the metaphase spread. Therefore, because bone marrow cells have a longer cell cycle time than stimulated lymphocytes, a minimum of 7-8 h culture after release of the block is recommended to give optimum results. It was also found that to increase the yield of mitoses, at least 6-8 h of growth is necessary before the addition of either of these synchronizing agents.
Pathology (1983), 15, January favourably to the use of visual aids and stated a preference for early referral to genetic counsellors. Of 72% of consultands who were satisfied with genetic counselling, 25% said that they would appreciate a followup appointment. SAETHRE-CHOTZEN SYNDROME AND ITS RELATIONSHIP TO OTHER CRANIOSYNOSTOSES J. WHITE, L. J. SHEFFIELD,D. A. SIMPSON& D. J. DAVID South
Australian Cranio Facial Unit Saethre Chotzen Syndrome is a dominantly inherited syndrome with variable ‘features including craniosynostosis, facial asymmetry, low set frontal hairline, ptosis and soft tissue syndactyly. Review of 7 cases of the syndrome referred to the South Australian Cranio Facial Unit showed a positive family history in all but 2 cases. There was wide variability of expression both between and within families. Craniosynostosis was present in 5 cases. all of which had at least coronal synostosis. Facial asymmetry was present in 6 cases, and syndactyly was minimal if present. Ptosis, malocclusions and nasal septa1 deviation were common features. Several other cases with craniosynostosis caused diagnostic problems, as there appears to be some overlap between Saethre Chotzen Syndrome, Crouzon Syndrome and Craniofrontonasal Dysplasia. Early diagnosis, combined with genetic counselling and craniofacial surgery should minimize the eventual deformity and long term effects on the family. A DEFECT IN COBALAMIN (VITAMIN 812) METABOLISM ASSOCIATED WITH HOMOCYSTINURIA AND METHYLMALONIC AClDURlA BRIDGETWILCKEN.JUDITH HAMMOND& MARTIN SILINK Oliver Latham Laboratory. North Ryde & Royal Alexandra Hospital for
Children, Sydney
University of Melbourne, Department of Medicine, St Vincent’s Hospital, Melbourne If BrdU is incorporated into DNA during the latter stages of DNA synthesis, late replication banding patterns can be produced by exposure to light followed by incubation in a hot salt solution. This produces BrdU late replication R bands after staining in Giemsa. We have found that no pretreatment of the slides is necessary to produce banding if an alkaline phosphate buffered Giemsa solution is used for staining. However. this produces a reverse form of differentiation which results in late replication G-banding. We have found this technique very useful because ( I ) no pretreatment is required and the banding patterns are very clear; (2) slides can be differentiated immediately and even 12 mth old slides can be satisfactorily differentiated; (3) slides cannot be overtreated, therefore this is a useful procedure when only a few preparations are available for banding; and (4) slides may be sequentially stained R G or G C. The poster describes and illustrates this banding technique.
A girl aged 10% yr had suffered lethargy and intellectual deterioration for 6 mth. Urinary metabolic screening revealed homocystinuria and methylmalonic aciduria. The hemoglobin level was 12 d d l , the bone marrow showed megaloblastic changes, but serum levels of B,*, folate and transcobalamins I and I1 were normal. Genetic complementation studies on a cell line cultured from skin fibroblasts revealed a defect in cobalamin metabolism of the Cbl C class. In man only 2 reactions require a coenzyme form of vitamin B,2: the remethylation of homocysteine to methionine requires methyl cobalamin, and the formation of succinyl CoA from L methylmalonlyl CoA requires adenosyl cobalamin. Of the 6 published cases of homocystinuria with methylmalonic aciduria due to an inborn error of cobalamin metabolism, four have been assigned to the complementation group ‘Cbl C‘. Two patients died in infancy, despite B,, therapy, one died aged 7 yr, and one presented with lethargy and delayed development at 18 mth, but is well aged 12 yr with B,* therapy. All 3 patients who came to autopsy showed atherosclerotic lesions in small arteries. Our patient appears to have a mild form of the Cbl C defect of cobalamin metabolism. On treatment with I.M. cyanocobalamin her plasma homocystine level and urinary methylmalonic acid excretion decreased but remained abnormal, her lethargy vanished and her mental and physical progress is normal after one yr. The long term outlook must remain uncertain, particularly in relation to atherosclerosis.
A FOLLOW-UP EVALUATION OF A GENETIC COUNSELLING SERVICE P. WHITE & L. J. SHEFFIELD Adelaide Children’s Hospital and
CYSTIC FIBROSIS SCREENING OF 41 000 NEONATES, USING A DRIED BLOOD SPOT IMMUNO-REACTIVE TRYPSIN ASSAY BRIDGETWILCKEN,RUTH URWIN,A. R. D. BROWN& D. A. BROWN
SEQUENTIAL LATE REPLICATION R AND G BANDING PAlTERNS
LORNA M. WEBBER& 0. MARGARETGARSON Cytogenetic Unit,
Flinders University Medical School Fifty individuals or families who have received genetic counselling over a 7 mth period were personally interviewed for a follow-up study of the genetic counselling service. The interview took place 12-19 mth after counselling. 86% of those interviewed had some understanding of their condition and 48% claimed that genetic counselling had directly increased their ability to cope. This understanding was shown to be promoted by the sending of a letter summarizing the contents of the genetic counselling session. 64% had a good recall of the risk figure quoted and in 73% of those interviewed the consultand‘s perception of whether the risk was high or low was identical to the genetic counsellors as recorded in the genetic records. This perception of risk had little effect on the couples’ attitude to having more children whilst it seemed that the perceived burden was more important. The consultands generally reacted
Oliver Latharn Laboralorv, N.S. W. Health Commission
A reliable screening test for cystic fibrosis (CF) has long been sought. Recently Crossley, Elliott & Smith showed elevated blood immunoreactive trypsin (IRT) levels in neonates with CF, and developed a radioimmunoassay for IRT in dried blood spots. In N.S.W. we used Crossley’s reagents and a modified method to screen 41 000 babies. IRT was elevated in 237, and 203 repeat blood samples have so far been received. Twenty-one babies had persistently elevated IRT. and CF was confirmed in all by sweat testing. Of the 21 CF babies, 6 had meconium ileus and 3 had a sibling with CF, but in 12 the diagnosis was unsuspected. Three C F babies had normal stool trypsin, suggesting that the test will identify patients with adequate pancreatic function. No missed cases are yet known. In retrospective studies of blood spot samples from 36 newborns later