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The cytogenetics of bone marrow transplantation
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I Ht H L L I A h G t N t ' I I C S S O C l t T j ' Ot- S U S T K L . A S I . 4
referred in the newborn period. Thi\ is in addition to 50 patients w i t h arthrogrypoiic multiplex congenita amongst 253 patienth with multiple congenital contractures of various causes. In t h e newborn population. 7 were stillborn, 9 died neonatally. 3 died between 2 mth and 2 yr after birth and 13 survived with apparently good health. Results indicate that only 3 patients had true AMC of whom 2 had died, but the remainder comprised various conditions thereby indicating the need for an individualized approach in the newborn uith multiple congenital contractures. Lethal pterygium syndromes. other contractural syndromes known to be associated with early lethality, chromosomal disorders and intrauterine infection were main causes for early lethality.
WESTERN AUSTRALIAN EXPERIENCE IN PRENATAL DIAGNOSIS OF HERITABLE METABOLIC DISORDERS Rot.%.ioH4tnf.I . \ \ I ) ST.\\J. W \ i o C h i L'niversitj Depuritnent oJ Obstetrics and G.vtiueco1og.v. King Edward ,Metnorial Hospital ,for M'omen, Prrth
Prenatal diagnosit ot inborn errors of metabolism is becoming an increasingly important service to modern obstetric practice. Whereas in the early seventier an amniocentesis to determine tetal risk for an inherited dkorder was a rare occurrence in our hospital, now we are monitoring high-risk pregnancies every month or two. This increase in the number of prenatal tests is due to several factors. including the elucidation o f the enzyme defects in many of the inborn errors of metabolism. increased clinician and patient awareness of the availability of the diagnostic senice and the more frequent identification of index cases ot genetic disorder5 i n biblings. In this report we Hish to present the experience of o u r laboratory at King Ed\\ard Memorial Hospital in carrying out prenatal diagnoses of heritable biochemical disorders in the period 1978-1982. During these 5 y r we found biochemical ecidence of 3 fetuses affected by Pompe's disease and h g l e cases of fetuses with metachromatic leukodystrophy. Maroteaux-Lamy syndrome, ray-Sachs disease and X-linked ichthyosis. 'The diagnoses were confirmed by studies of fetal tissues from 5 aborted fetuses. 4 rixth pregnancy proceeded to term, and the diagnosis was supported by clinical e\idence of the condition (ichthyosis) in the infant.
IS TWINNING THE MOST COMMON CONGENITAL ABNORMALITY? D % V I D .A. H \ \ . Pqi.i.ihi J . O'BRIES %\D C\ROL Jolissroc Departnierit of Genetics and Hirrnan Variation, L a Trobe L'niuer>itj, Melbourne
While one child in 50 is a ruin, the focus on twins in genetic analysis diverts attention from the specific problems accompanying a multiple birth. I n the preschool years twins are delayed physically and intellectually. particularl) in the area of language development. The 1.a Trobe Twin Study of Behavioural and Biological Development seeks to identify those areas where deficits remain and those nvins most at risk for particular problems. In this paper 2 such groups are examined. Firstly, male twins where speech problems are common and are linked to reading disab persist throughout school to the extent that by age 14 only 42Vo of them achieve adequate vandards of literacy compared with 70Vo of singleton boys. 4 1 1 explanation combines social effects of the twin situation o n language deLeloprnent with altered hemispheric specialisation, particularly in monochorionic hlZ twins. Secondly, the second-born twin is much more distractable and has several specific cognitive defects. The intrauterine hypoxia explanation for birth order effects is contrasted with one in terms ot different parental expectations of the first and cecond twin. These data are combined to create a "continuum of risk" indeh to identify high risk twins, and several strategies of early intervention are examined M hich are currently being tried with these children at La Trobe.
Pathology (1984), 16, January
THE CYTOGENETICS OF BONE MARROW TRANSPLANTATION R. P . HERRMANN, B. F. M E Y E K L , . CHIPI'EK A N D K . ment of Haernatology. Royal Perth Hospital
POTTS
Depart-
Allogeneic bone marrow transplantation has been performed in 9 patients in o u r Department over the past 3 yr. I n 3 instances the donor \\as of a different sex 1 0the recipient and cytogenetic transformation of marrow cells and stimulated blood lymphocytes was demonstrated. In one case increased centromeric heterochromatin in chromosome No. I was present initially i n the recipient and this was not present following transplantation. In this pair a marker C group chromosome was present in the donor which was demonstrated in the recipient subsequent to transplantation. In a further 4 patients blood group differences between donor and recipient allowed determination of engraftment. I t was not possible to determine engraftment in one patient, a full blood Aboriginal female aged 8 yr. Because of the possibility of autologous bone marrow reconstitution it is important to document marrow engraftment, and cytogenetic sex differences or heteromorphism are useful markers. Where these are not able to be used red cell antigens, gamma globulin allotypes or complement allotypes may demonstrate engraftment. I f the transplant is performed for leukemia, recurrence of leukemia may be demonstrated by the redevelopment of an abnormal cell line in either donor or recipient cells.
EFFECT OF PARENTAL BIRTH PLACE ON BIRTH INCIDENCE OF NEURAL TUBE DEFECTS IN WESTERN AUSTRALIAGENES OR ENVIRONMENT? M. S. T . H o a w AND CAROI-BOWR University Deparlriient of ,Medicine, Universit.v of Western Airstrulia This study was conducted to investigate the birth incidence of neural tube (NT) defects in Western Australia, in relation to parental birthplace. Cases of anencephaly, spina bifida and encephalocele were identified from perinatal death certificates and hospital records in Western Australia, for the years 1966 to 1981. Information on parental birthplace was obtained from the birth notification paper for each case. There has been a statistically significant fall in birth incidence of NTD from 1970 to 1981, which is not accounted for by demographic changes in maternal age or parity. The incidence of NTD was found to vary according to parental birthplaces, being highest when one parent was born in the British Isles and one in Australia (3.0 per lo00 births) and lowest when both were born in other European countries (0.9 per 1000 births). The incidence in Australian parents was 1.8 per I000 births and 2 . 2 per 1000 births when both parents were British born.
ADACTYLIA AGLOSSIA SYNDROME-A CASE PRESENTATION ATHEI HOCKEYA N D I A N WALPOLE Genetic Clinic, King Edward .Memorial Hospital for Women, Perih A young woman aged 21 yr presented for genetic counselling when pregnant for the first time. She was the 4th child with 3 older brothers and a miscarriage. She was born with absence defects of her right hand with only part of the carpus remaining, symphangelism of the index and middle finger of the left hand, absence of toes on the right foot and absence of tarsals and toes and a shortening of the left leg. She had features in common with 60 other reported cases of AAS. Her pregnancy was monitored by ultrasound and an unaffected daughter born. Inheritance is unknown, possibly in this case either sporadic or dominant new mutation. The pedigree-clinical photographs and a table of defects are presented.
I Ht H L L I A h G t N t ' I I C S S O C l t T j ' Ot- S U S T K L . A S I . 4
referred in the newborn period. Thi\ is in addition to 50 patients w i t h arthrogrypoiic multiplex congenita amongst 253 patienth with multiple congenital contractures of various causes. In t h e newborn population. 7 were stillborn, 9 died neonatally. 3 died between 2 mth and 2 yr after birth and 13 survived with apparently good health. Results indicate that only 3 patients had true AMC of whom 2 had died, but the remainder comprised various conditions thereby indicating the need for an individualized approach in the newborn uith multiple congenital contractures. Lethal pterygium syndromes. other contractural syndromes known to be associated with early lethality, chromosomal disorders and intrauterine infection were main causes for early lethality.
WESTERN AUSTRALIAN EXPERIENCE IN PRENATAL DIAGNOSIS OF HERITABLE METABOLIC DISORDERS Rot.%.ioH4tnf.I . \ \ I ) ST.\\J. W \ i o C h i L'niversitj Depuritnent oJ Obstetrics and G.vtiueco1og.v. King Edward ,Metnorial Hospital ,for M'omen, Prrth
Prenatal diagnosit ot inborn errors of metabolism is becoming an increasingly important service to modern obstetric practice. Whereas in the early seventier an amniocentesis to determine tetal risk for an inherited dkorder was a rare occurrence in our hospital, now we are monitoring high-risk pregnancies every month or two. This increase in the number of prenatal tests is due to several factors. including the elucidation o f the enzyme defects in many of the inborn errors of metabolism. increased clinician and patient awareness of the availability of the diagnostic senice and the more frequent identification of index cases ot genetic disorder5 i n biblings. In this report we Hish to present the experience of o u r laboratory at King Ed\\ard Memorial Hospital in carrying out prenatal diagnoses of heritable biochemical disorders in the period 1978-1982. During these 5 y r we found biochemical ecidence of 3 fetuses affected by Pompe's disease and h g l e cases of fetuses with metachromatic leukodystrophy. Maroteaux-Lamy syndrome, ray-Sachs disease and X-linked ichthyosis. 'The diagnoses were confirmed by studies of fetal tissues from 5 aborted fetuses. 4 rixth pregnancy proceeded to term, and the diagnosis was supported by clinical e\idence of the condition (ichthyosis) in the infant.
IS TWINNING THE MOST COMMON CONGENITAL ABNORMALITY? D % V I D .A. H \ \ . Pqi.i.ihi J . O'BRIES %\D C\ROL Jolissroc Departnierit of Genetics and Hirrnan Variation, L a Trobe L'niuer>itj, Melbourne
While one child in 50 is a ruin, the focus on twins in genetic analysis diverts attention from the specific problems accompanying a multiple birth. I n the preschool years twins are delayed physically and intellectually. particularl) in the area of language development. The 1.a Trobe Twin Study of Behavioural and Biological Development seeks to identify those areas where deficits remain and those nvins most at risk for particular problems. In this paper 2 such groups are examined. Firstly, male twins where speech problems are common and are linked to reading disab persist throughout school to the extent that by age 14 only 42Vo of them achieve adequate vandards of literacy compared with 70Vo of singleton boys. 4 1 1 explanation combines social effects of the twin situation o n language deLeloprnent with altered hemispheric specialisation, particularly in monochorionic hlZ twins. Secondly, the second-born twin is much more distractable and has several specific cognitive defects. The intrauterine hypoxia explanation for birth order effects is contrasted with one in terms ot different parental expectations of the first and cecond twin. These data are combined to create a "continuum of risk" indeh to identify high risk twins, and several strategies of early intervention are examined M hich are currently being tried with these children at La Trobe.
Pathology (1984), 16, January
THE CYTOGENETICS OF BONE MARROW TRANSPLANTATION R. P . HERRMANN, B. F. M E Y E K L , . CHIPI'EK A N D K . ment of Haernatology. Royal Perth Hospital
POTTS
Depart-
Allogeneic bone marrow transplantation has been performed in 9 patients in o u r Department over the past 3 yr. I n 3 instances the donor \\as of a different sex 1 0the recipient and cytogenetic transformation of marrow cells and stimulated blood lymphocytes was demonstrated. In one case increased centromeric heterochromatin in chromosome No. I was present initially i n the recipient and this was not present following transplantation. In this pair a marker C group chromosome was present in the donor which was demonstrated in the recipient subsequent to transplantation. In a further 4 patients blood group differences between donor and recipient allowed determination of engraftment. I t was not possible to determine engraftment in one patient, a full blood Aboriginal female aged 8 yr. Because of the possibility of autologous bone marrow reconstitution it is important to document marrow engraftment, and cytogenetic sex differences or heteromorphism are useful markers. Where these are not able to be used red cell antigens, gamma globulin allotypes or complement allotypes may demonstrate engraftment. I f the transplant is performed for leukemia, recurrence of leukemia may be demonstrated by the redevelopment of an abnormal cell line in either donor or recipient cells.
EFFECT OF PARENTAL BIRTH PLACE ON BIRTH INCIDENCE OF NEURAL TUBE DEFECTS IN WESTERN AUSTRALIAGENES OR ENVIRONMENT? M. S. T . H o a w AND CAROI-BOWR University Deparlriient of ,Medicine, Universit.v of Western Airstrulia This study was conducted to investigate the birth incidence of neural tube (NT) defects in Western Australia, in relation to parental birthplace. Cases of anencephaly, spina bifida and encephalocele were identified from perinatal death certificates and hospital records in Western Australia, for the years 1966 to 1981. Information on parental birthplace was obtained from the birth notification paper for each case. There has been a statistically significant fall in birth incidence of NTD from 1970 to 1981, which is not accounted for by demographic changes in maternal age or parity. The incidence of NTD was found to vary according to parental birthplaces, being highest when one parent was born in the British Isles and one in Australia (3.0 per lo00 births) and lowest when both were born in other European countries (0.9 per 1000 births). The incidence in Australian parents was 1.8 per I000 births and 2 . 2 per 1000 births when both parents were British born.
ADACTYLIA AGLOSSIA SYNDROME-A CASE PRESENTATION ATHEI HOCKEYA N D I A N WALPOLE Genetic Clinic, King Edward .Memorial Hospital for Women, Perih A young woman aged 21 yr presented for genetic counselling when pregnant for the first time. She was the 4th child with 3 older brothers and a miscarriage. She was born with absence defects of her right hand with only part of the carpus remaining, symphangelism of the index and middle finger of the left hand, absence of toes on the right foot and absence of tarsals and toes and a shortening of the left leg. She had features in common with 60 other reported cases of AAS. Her pregnancy was monitored by ultrasound and an unaffected daughter born. Inheritance is unknown, possibly in this case either sporadic or dominant new mutation. The pedigree-clinical photographs and a table of defects are presented.