184 with other forms of underlying chronic pulmonary disease. This would be a major indication for an immediate chest X-ray. Subcutaneous emphysema would be another indication for a chest X-ray, since this may occur in asthma in the absence of a pneumothorax. Routine auscultation and palpation signs of pneumothorax are undependable in asthma, but in a crisis the results of needle aspiration can be convincing. Rutgers Medical School, Piscataway, New Jersey 08854, U.S.A.
MONROE S. KARETZKY.
EFFECT OF OPERATING-THEATRE TEMPERATURES ON THE SETTING-TIMES OF ACRYLIC CEMENTS FOR USE IN ORTHOPAEDIC SURGERY SiR,—The use of acrylic cements is well established in orthopaedic surgery, but few data appear to have been published on the acceleration of the setting-time as a function of increasing the theatre ambient temperature. Measurements have been carried out using unsterilised CMW bone cement to establish the relationship between the setting-time (corresponding approximately to the maximum temperature reached during setting) and the temperature at which the polymerisation was being carried out. Under carefully controlled conditions it was found that the time to set varied with temperature of polymerisation as follows: 77 59 68 (°F) 15 20 25 (°C) 7-5 4-9 12-6 Setting-time (min.) Thus between 68 °F and 77 °F there is
86 30 3-3
Ambient temp. Ambient temp.
95 35 2-5
reduction in setting-time of approximately 34%, and this may be vital during the manipulation and insertion of the cement into the prepared bone cavity. We recommend that, in order to achieve a desirable extension of setting-time, the unmixed components of the cement should not be stored in the operating-theatre, but be refrigerated to approximately 0°C for a period of 10 minutes before mixing in order to prolong the handlingtime if so desired. G. P. PEARSON School of Polymer Science, D. F. JONES. University of Bradford. Rheumatism Research Unit, University of Leeds.
a
V. WRIGHT.
ENDEMIC GOITRE AND CRETINISM to
SiR,—Your important editorial (March 15, p. 619) fails mention endemic cretinism as a major indicator for
urgency in
embarking on a programme for correction of iodine deficiency. The presence of this condition, now demonstrated to be due to severe iodine deficiency and preventable by its correction, makes an iodisation programme mandatory.l,2In the absence of cretinism there is less urgency, even though the benefits of an iodisation programme are substantial in prevention of morbidity. Endemic cretinism occurs only with severe iodine deficiency associated with more remote regions in endemic areasiodised oil has been shown to be a practicable and effective method where distribution of iodised salt is not possible. 3,44 Department of Social and Preventive
Medicine, Monash Medical School, Alfred Hospital, Prahran, Victoria 3181, Australia. 1. 2. 3.
BASIL S. HETZEL.
Lancet, 1972, ii, 365. Hetzel, B. S. N.Z. med. J. 1974, 80, 482. Stanbury, J. B., Ermans, A. M., Hetzel, B. S., Pretell, E. A., Querido, A. Wld Hlth Org. Chron. 1974, 28, 220. 4. Thilly, C. H., Delange, F., Goldstein-Golaire, J., Ermans, A. M. J. clin. Endocr. Metab. 1973, 36, 1196.
ALPHA-FETOPROTEIN AS AN INDICATOR OF FETAL CONDITION SiR,—Brock and Sutcliffe,! as well as others, have demonstrated the specific fetal antigen, alpha-fetoprotein (A.F.P.), to be a useful in-utero predictor of fetal neural-tube defects. Several investigators, using radioimmunoassay, have also suggested a correlation between elevated A.F.P. concentrations and fetal death or fetal compromise in pregnancies complicated by Rh disease and maternal diabetes. 2-5 For the past 3 years we have used a radial immunodiffusion technique to determine amniotic-fluid A.F.P. levels in secondtrimester patients whose fetuses were genetically at risk for neural-tube defects. In this preliminary study the immunodiffusion assay, sensitive to 165 ng. per ml., was utilised to determine A.F.P. concentrations in 80 amnioticfluid samples from second and third trimester patients whose pregnancies were either completely normal or complicated by toxasmia, diabetes, Rh immunisation, fetal anencephaly, or fetal death. In this study, the mean A.F.P. concentration in 26 samples from normal pregnancies between 15 and 18 weeks’ gestation was 8-6 g. per ml. (range 2-6-17-5 g. per ml.). In 11 samples from normal 19 to 22 weeks’ gestation, the A.F.P. levels varied between 2-4 and 9-1 g. per ml. (mean 4-2 jjg. per ml.). These findings agree with those of other investigators using radioimmunoassay. 6-8 It is of note that the only other second-trimester fluid sample, obtained from a 19-week pregnancy complicated by trisomy 18, severe Rh sensitisation, and fetal death, revealed an A.F.P. concentration of 16.2 g. per ml., which was elevated but not outside the 95% confidence limit. The results obtained from 40 patients in the third trimester are summarised in the figure. With the exception of 2 samples from anencephalic pregnancies, where A.F.P. concentrations were well above 20 g. per ml., all other A.F.P. levels obtained after the 32nd week of gestation were less than 0-8 tg. per ml. A.F.P. concentrations in all 10 normal pregnancies between the 36th and 40th week of gestation were undetectable (< 165 ng. per ml.), also correlating with published radioimmunoassay data.9 The mean A.F.P. levels in 15 samples from diabetic patients between 36 and 40 weeks of gestation were significantly higher than in the normal controls (p < 0-0005). Concentrations in toxeemic pregnancies were raised, but the number of samples precluded statistical evaluation. A.F.P. levels from our 6 Rh-sensitised pregnancies were not raised in comparison with other published data from normal pregnancies at the same stage of gestation.88 These preliminary data from a small but representative normal and high-risk sampling agree with the results of other investigators using the more sensitive but more ’
complex radioimmunoassay. Our results further confirm a tenfold increase in A.F.P. levels in anencephalic pregnancies noted by other investigators.1, 2,10,11 Furthermore, this study suggests a correlation between elevated A.F.P. levels and certain abnormal condiBrock, D. J. H., Sutcliffe, R. G. Lancet, 1972, ii, 197. Higa, Y., Sasazuki, T., Nakajima, H., Takayama, M., Tada, M., Soma, H. Am. J. Obstet. Gynec. 1974, 119, 932. 3. Norgaard-Pederson, B., Klebe, J. G. Acta endocr., Copenh. suppl., 1974, 182, 81. 4. Seppälä, M., Ruoslahti, E. Obstet. Gynec., N.Y. 1973, 42, 701. 5. Seppälä, M., Ruoslahti, E. Lancet, 1973, i, 155. 6. Allen, L. D., Ferguson-Smith, M. A., Donald, I., Sweet, E. M., Gibson, A. A. M. ibid. 1973, ii, 522. 7. Hull, E. W., Carbones, P. P., Moertel, C. G., O’Conor, G. T. ibid. 1970, i, 779. 8. Seppälä, M., Ruoslahti, E. Am. J. Obstet. Gynec. 1972, 114, 595. 9. Seller, M. J., Coltart, T. M., Campbell, S., Singer, J. D. Lancet, 1973, i, 73. 10. Harris, R., Jennison, R. F., Barson, A. J., Laurence, K. M., Ruoslahti, E., Seppälä, M. ibid. 1974, i, 429. 11. Purves, L. R., Branch, W. R., Boes, E. G. M. ibid. 1967, i, 1007. 1. 2.
185 tions of pregnancy, such as maternal diabetes and toxaemia. However, more third-trimester pregnancies must obviously be studied to validate these suggestions. Our experience with the assay by radial immunodiffusion also suggests that it may be possible for centres not capable of performing more complicated assays to obtain information about fetal wellbeing by the simple immunodiffusion assay. Department of Obstetrics and Gynecology. Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
H. HOLTER J. C. HOBBINS. A. BAUMGARTEN.
mg. procaine in all were infused in portions of 500 mg. per 5 minutes. During this treatment the rigidity slowly disappeared. The heart-rate and rhythm and the rectal temperature became normal, and the systolic blood-pressure remained steady around 100-110 mm. Hg. The comparison of this case with that of MacLachlan and Forrest made us wonder if procaine should be withheld until enough bicarbonate has been infused. The original regimen of Harrison 13 lists bicarbonate before procainea routine re-emphasised by Maisel et al.14 Britt,I5 however, advocates procaine before the correction of the acidosis. The timing of the administration of procaine might be of some importance. If this is the case, what is the correct
minutes, 3500
sequence ? GENETIC EFFECTS OF HYPERTHERMIA SiR,—Several of your contributors 1-4 have described the effects of hyperthermia on the occurrence, growth, and destruction of tumours. I should like to draw attention to some of the genetic effects of hyperthermia, since they may be relevant to these observations. Hyperthermia has been shown to induce chromosome damage and gene mutations in a wide range of organisms.5,6 There is also evidence that raised temperatures induce several types of D.N.A. damage, such as depurination and strand breaks, which are similar to those produced by ionising radiation and alkylating agents.’.88 Furthermore, many radiation-sensitive mutants of microorganisms are cross-sensitive to raised temperatures, again indicating that these agents produce similar types of ’damage. 9-11 This similarity between the lethal and mutagenic effects of hyperthermia and ionising radiation suggests that the mechanisms by which they kill tumour cells and induce tumours may also be similar. Department of Medicine, Welsh National School of Medicine, Heath Park, Cardiff.
W. EMRYS EVANS.
PROCAINE AND MALIGNANT HYPERTHERMIA
SiR,—The fatal hypotension after procaine in malignant hyperthermia reported by MacLachlan and Forrest 12 made us wonder why this drug in a dose of 3-5 g. seemed to benefit our patient without a fall in blood-pressure. A 15-year-old healthy boy underwent operation for a fracture of his tibial tuberosity. After thiopentone-suxamethonium induction, anaesthesia was maintained with nitrous oxide and 1/2-1 % halothane. About 30 minutes after induction he developed hyperthermia (rectal temperature 40°C), severe rigidity, tachycardia (180 per minute) with irregular pulse, and fall in blood-pressure to shock levels. After infusion of bicarbonate, lanatocid, hydrocortisone, and Ringer lactate, together with intensive cooling, the circulation improved, and the systolic blood-pressure stabilised at 100 mm. Hg. By this time the blood-gases had reached normal levels. However, because of persisting severe rigidity, together with cardiac irregularities, a tachycardia of 130-140 per minute and a rectal temperature of 39.6OC, we infused procaine. In the course of 60 1. 2. 3. 4.
5. 6. 7. 8. 9.
10. 11. 12.
Brunning, D. A. Lancet, 1974, i, 272. Holman, R. A. ibid. 1975, i, 1027. Teasdale, C. ibid. p. 852. Turnbull, A. R. ibid. p. 643. Lindegren, D. Heredity, 1972, 70, 165. Evans, W. E., Parry, J. M. ibid. (in the press). Woodcock, E., Griggs, G. W. Nature New Biol. 1972, 237, 76. Lindahl, T., Nyberg, B. Biochemistry, 1972, 11, 3611. Bridges, B. A., Ashworth-Smith, M. J., Munson, R. T. Biochim. Biophys. Res Comm. 1969, 35, 192. Evans, W. E., Parry, J. M. Molec. gen. Genet. 1972, 118, 261. Evans, W. E., Parry, J. M. ibid. 1974, 134, 333. MacLachlan, D., Forrest, A. L. Lancet, 1974, i, 355.
Central Hospital, Hamar, and
BJÖRN HÖIVIK JACOB STOVNER.
University Hospital, Oslo, Norway.
RHIZOMELIA WITH DIGITAL ANOMALY SIR,-A recurring problem in genetic counselling is that of the couple who have had an infant who was stillborn or who died in the perinatal period and who was noted to have short limbs. Such infants frequently have the diagnostic label of achondroplasia attached to them; but true achondroplasia is rarely, if ever, a cause of perinatal death. The differential diagnosis of such cases includes several rare diseases such as achondrogenesis of Parenti type, asphyxiating thoracic dysplasia, chondrodysplasia punctata (Conradi’s disease), and diastrophic dwarfism. All these diseases are inherited in an autosomal recessive manner. Thanatophoric dwarfism, of unknown aetiology, is also seen in this situation; and severe hypophosphatasia, another recessive disorder, can mimic this picture. Unfortunately, for the problem of advising parents regarding further children, death stills the clinician’s interest and all too often no clinical photographs or radiographs are taken and it is impossible to make a retrospective diagnosis. At other times, abnormalities are recorded that are not compatible with any known disorder and the pattern of inheritance, if any, is unknown. It is important to record all familial instances of such cases so that they can be compared with others and new inherited disorders
recognised. I have seen such a family in which rhizomelia associated with variable digital anomaly occurred in two sibs. Investigation was incomplete but the clinical features were sufficiently characteristic to exclude known disorders. case was a stillborn boy born in 1971, the first child 34-year-old mother. The father was aged 37 and unrelated to the mother, he being West Indian and she of English parentage. The pregnancy was normal apart from a slight ante-partum haemorrhage at 38 weeks. The child was born at term following a breech presentation, was macerated, and weighed 1-434 kg. A post-mortem report describes the infant as having proximal shortening of all limbs, a large head with hydrocephalus, and symmetrical anomalies of the digits consisting of two middle digits only on each hand and a prehensile type of big toe with a wide gap and then two lateral digits on each foot. The heart, lungs, liver, spleen, and kidneys were all present and showed no malformation. The body was too macerated for chromosome analysis. No radiographs were taken, apart from a prenatal X-ray showing short fetal femur and a short humerus. The mother was seen for genetic counselling and was advised that the risk of recurrence was less than 1%. A second child, a normal boy, was born in 1972.
The first
of
a
"
"
The second case was a third son, born in March, 1975, who died at 1 hours. He was delivered by lower-segment caesarean section at 36 weeks of pregnancy because of falling maternal Harrison, G. G. Br. med. J. 1971, iii, 454. Maisel, H. R., Sessions, D. G., Miller, R. N. Ann. Otolar. 1973, 82, 729. 15. Britt, B. A. Anesth. Analg. 1972, 51, 841.
13. 14.
MONROE S. KARETZKY.
EFFECT OF OPERATING-THEATRE TEMPERATURES ON THE SETTING-TIMES OF ACRYLIC CEMENTS FOR USE IN ORTHOPAEDIC SURGERY SiR,—The use of acrylic cements is well established in orthopaedic surgery, but few data appear to have been published on the acceleration of the setting-time as a function of increasing the theatre ambient temperature. Measurements have been carried out using unsterilised CMW bone cement to establish the relationship between the setting-time (corresponding approximately to the maximum temperature reached during setting) and the temperature at which the polymerisation was being carried out. Under carefully controlled conditions it was found that the time to set varied with temperature of polymerisation as follows: 77 59 68 (°F) 15 20 25 (°C) 7-5 4-9 12-6 Setting-time (min.) Thus between 68 °F and 77 °F there is
86 30 3-3
Ambient temp. Ambient temp.
95 35 2-5
reduction in setting-time of approximately 34%, and this may be vital during the manipulation and insertion of the cement into the prepared bone cavity. We recommend that, in order to achieve a desirable extension of setting-time, the unmixed components of the cement should not be stored in the operating-theatre, but be refrigerated to approximately 0°C for a period of 10 minutes before mixing in order to prolong the handlingtime if so desired. G. P. PEARSON School of Polymer Science, D. F. JONES. University of Bradford. Rheumatism Research Unit, University of Leeds.
a
V. WRIGHT.
ENDEMIC GOITRE AND CRETINISM to
SiR,—Your important editorial (March 15, p. 619) fails mention endemic cretinism as a major indicator for
urgency in
embarking on a programme for correction of iodine deficiency. The presence of this condition, now demonstrated to be due to severe iodine deficiency and preventable by its correction, makes an iodisation programme mandatory.l,2In the absence of cretinism there is less urgency, even though the benefits of an iodisation programme are substantial in prevention of morbidity. Endemic cretinism occurs only with severe iodine deficiency associated with more remote regions in endemic areasiodised oil has been shown to be a practicable and effective method where distribution of iodised salt is not possible. 3,44 Department of Social and Preventive
Medicine, Monash Medical School, Alfred Hospital, Prahran, Victoria 3181, Australia. 1. 2. 3.
BASIL S. HETZEL.
Lancet, 1972, ii, 365. Hetzel, B. S. N.Z. med. J. 1974, 80, 482. Stanbury, J. B., Ermans, A. M., Hetzel, B. S., Pretell, E. A., Querido, A. Wld Hlth Org. Chron. 1974, 28, 220. 4. Thilly, C. H., Delange, F., Goldstein-Golaire, J., Ermans, A. M. J. clin. Endocr. Metab. 1973, 36, 1196.
ALPHA-FETOPROTEIN AS AN INDICATOR OF FETAL CONDITION SiR,—Brock and Sutcliffe,! as well as others, have demonstrated the specific fetal antigen, alpha-fetoprotein (A.F.P.), to be a useful in-utero predictor of fetal neural-tube defects. Several investigators, using radioimmunoassay, have also suggested a correlation between elevated A.F.P. concentrations and fetal death or fetal compromise in pregnancies complicated by Rh disease and maternal diabetes. 2-5 For the past 3 years we have used a radial immunodiffusion technique to determine amniotic-fluid A.F.P. levels in secondtrimester patients whose fetuses were genetically at risk for neural-tube defects. In this preliminary study the immunodiffusion assay, sensitive to 165 ng. per ml., was utilised to determine A.F.P. concentrations in 80 amnioticfluid samples from second and third trimester patients whose pregnancies were either completely normal or complicated by toxasmia, diabetes, Rh immunisation, fetal anencephaly, or fetal death. In this study, the mean A.F.P. concentration in 26 samples from normal pregnancies between 15 and 18 weeks’ gestation was 8-6 g. per ml. (range 2-6-17-5 g. per ml.). In 11 samples from normal 19 to 22 weeks’ gestation, the A.F.P. levels varied between 2-4 and 9-1 g. per ml. (mean 4-2 jjg. per ml.). These findings agree with those of other investigators using radioimmunoassay. 6-8 It is of note that the only other second-trimester fluid sample, obtained from a 19-week pregnancy complicated by trisomy 18, severe Rh sensitisation, and fetal death, revealed an A.F.P. concentration of 16.2 g. per ml., which was elevated but not outside the 95% confidence limit. The results obtained from 40 patients in the third trimester are summarised in the figure. With the exception of 2 samples from anencephalic pregnancies, where A.F.P. concentrations were well above 20 g. per ml., all other A.F.P. levels obtained after the 32nd week of gestation were less than 0-8 tg. per ml. A.F.P. concentrations in all 10 normal pregnancies between the 36th and 40th week of gestation were undetectable (< 165 ng. per ml.), also correlating with published radioimmunoassay data.9 The mean A.F.P. levels in 15 samples from diabetic patients between 36 and 40 weeks of gestation were significantly higher than in the normal controls (p < 0-0005). Concentrations in toxeemic pregnancies were raised, but the number of samples precluded statistical evaluation. A.F.P. levels from our 6 Rh-sensitised pregnancies were not raised in comparison with other published data from normal pregnancies at the same stage of gestation.88 These preliminary data from a small but representative normal and high-risk sampling agree with the results of other investigators using the more sensitive but more ’
complex radioimmunoassay. Our results further confirm a tenfold increase in A.F.P. levels in anencephalic pregnancies noted by other investigators.1, 2,10,11 Furthermore, this study suggests a correlation between elevated A.F.P. levels and certain abnormal condiBrock, D. J. H., Sutcliffe, R. G. Lancet, 1972, ii, 197. Higa, Y., Sasazuki, T., Nakajima, H., Takayama, M., Tada, M., Soma, H. Am. J. Obstet. Gynec. 1974, 119, 932. 3. Norgaard-Pederson, B., Klebe, J. G. Acta endocr., Copenh. suppl., 1974, 182, 81. 4. Seppälä, M., Ruoslahti, E. Obstet. Gynec., N.Y. 1973, 42, 701. 5. Seppälä, M., Ruoslahti, E. Lancet, 1973, i, 155. 6. Allen, L. D., Ferguson-Smith, M. A., Donald, I., Sweet, E. M., Gibson, A. A. M. ibid. 1973, ii, 522. 7. Hull, E. W., Carbones, P. P., Moertel, C. G., O’Conor, G. T. ibid. 1970, i, 779. 8. Seppälä, M., Ruoslahti, E. Am. J. Obstet. Gynec. 1972, 114, 595. 9. Seller, M. J., Coltart, T. M., Campbell, S., Singer, J. D. Lancet, 1973, i, 73. 10. Harris, R., Jennison, R. F., Barson, A. J., Laurence, K. M., Ruoslahti, E., Seppälä, M. ibid. 1974, i, 429. 11. Purves, L. R., Branch, W. R., Boes, E. G. M. ibid. 1967, i, 1007. 1. 2.
185 tions of pregnancy, such as maternal diabetes and toxaemia. However, more third-trimester pregnancies must obviously be studied to validate these suggestions. Our experience with the assay by radial immunodiffusion also suggests that it may be possible for centres not capable of performing more complicated assays to obtain information about fetal wellbeing by the simple immunodiffusion assay. Department of Obstetrics and Gynecology. Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
H. HOLTER J. C. HOBBINS. A. BAUMGARTEN.
mg. procaine in all were infused in portions of 500 mg. per 5 minutes. During this treatment the rigidity slowly disappeared. The heart-rate and rhythm and the rectal temperature became normal, and the systolic blood-pressure remained steady around 100-110 mm. Hg. The comparison of this case with that of MacLachlan and Forrest made us wonder if procaine should be withheld until enough bicarbonate has been infused. The original regimen of Harrison 13 lists bicarbonate before procainea routine re-emphasised by Maisel et al.14 Britt,I5 however, advocates procaine before the correction of the acidosis. The timing of the administration of procaine might be of some importance. If this is the case, what is the correct
minutes, 3500
sequence ? GENETIC EFFECTS OF HYPERTHERMIA SiR,—Several of your contributors 1-4 have described the effects of hyperthermia on the occurrence, growth, and destruction of tumours. I should like to draw attention to some of the genetic effects of hyperthermia, since they may be relevant to these observations. Hyperthermia has been shown to induce chromosome damage and gene mutations in a wide range of organisms.5,6 There is also evidence that raised temperatures induce several types of D.N.A. damage, such as depurination and strand breaks, which are similar to those produced by ionising radiation and alkylating agents.’.88 Furthermore, many radiation-sensitive mutants of microorganisms are cross-sensitive to raised temperatures, again indicating that these agents produce similar types of ’damage. 9-11 This similarity between the lethal and mutagenic effects of hyperthermia and ionising radiation suggests that the mechanisms by which they kill tumour cells and induce tumours may also be similar. Department of Medicine, Welsh National School of Medicine, Heath Park, Cardiff.
W. EMRYS EVANS.
PROCAINE AND MALIGNANT HYPERTHERMIA
SiR,—The fatal hypotension after procaine in malignant hyperthermia reported by MacLachlan and Forrest 12 made us wonder why this drug in a dose of 3-5 g. seemed to benefit our patient without a fall in blood-pressure. A 15-year-old healthy boy underwent operation for a fracture of his tibial tuberosity. After thiopentone-suxamethonium induction, anaesthesia was maintained with nitrous oxide and 1/2-1 % halothane. About 30 minutes after induction he developed hyperthermia (rectal temperature 40°C), severe rigidity, tachycardia (180 per minute) with irregular pulse, and fall in blood-pressure to shock levels. After infusion of bicarbonate, lanatocid, hydrocortisone, and Ringer lactate, together with intensive cooling, the circulation improved, and the systolic blood-pressure stabilised at 100 mm. Hg. By this time the blood-gases had reached normal levels. However, because of persisting severe rigidity, together with cardiac irregularities, a tachycardia of 130-140 per minute and a rectal temperature of 39.6OC, we infused procaine. In the course of 60 1. 2. 3. 4.
5. 6. 7. 8. 9.
10. 11. 12.
Brunning, D. A. Lancet, 1974, i, 272. Holman, R. A. ibid. 1975, i, 1027. Teasdale, C. ibid. p. 852. Turnbull, A. R. ibid. p. 643. Lindegren, D. Heredity, 1972, 70, 165. Evans, W. E., Parry, J. M. ibid. (in the press). Woodcock, E., Griggs, G. W. Nature New Biol. 1972, 237, 76. Lindahl, T., Nyberg, B. Biochemistry, 1972, 11, 3611. Bridges, B. A., Ashworth-Smith, M. J., Munson, R. T. Biochim. Biophys. Res Comm. 1969, 35, 192. Evans, W. E., Parry, J. M. Molec. gen. Genet. 1972, 118, 261. Evans, W. E., Parry, J. M. ibid. 1974, 134, 333. MacLachlan, D., Forrest, A. L. Lancet, 1974, i, 355.
Central Hospital, Hamar, and
BJÖRN HÖIVIK JACOB STOVNER.
University Hospital, Oslo, Norway.
RHIZOMELIA WITH DIGITAL ANOMALY SIR,-A recurring problem in genetic counselling is that of the couple who have had an infant who was stillborn or who died in the perinatal period and who was noted to have short limbs. Such infants frequently have the diagnostic label of achondroplasia attached to them; but true achondroplasia is rarely, if ever, a cause of perinatal death. The differential diagnosis of such cases includes several rare diseases such as achondrogenesis of Parenti type, asphyxiating thoracic dysplasia, chondrodysplasia punctata (Conradi’s disease), and diastrophic dwarfism. All these diseases are inherited in an autosomal recessive manner. Thanatophoric dwarfism, of unknown aetiology, is also seen in this situation; and severe hypophosphatasia, another recessive disorder, can mimic this picture. Unfortunately, for the problem of advising parents regarding further children, death stills the clinician’s interest and all too often no clinical photographs or radiographs are taken and it is impossible to make a retrospective diagnosis. At other times, abnormalities are recorded that are not compatible with any known disorder and the pattern of inheritance, if any, is unknown. It is important to record all familial instances of such cases so that they can be compared with others and new inherited disorders
recognised. I have seen such a family in which rhizomelia associated with variable digital anomaly occurred in two sibs. Investigation was incomplete but the clinical features were sufficiently characteristic to exclude known disorders. case was a stillborn boy born in 1971, the first child 34-year-old mother. The father was aged 37 and unrelated to the mother, he being West Indian and she of English parentage. The pregnancy was normal apart from a slight ante-partum haemorrhage at 38 weeks. The child was born at term following a breech presentation, was macerated, and weighed 1-434 kg. A post-mortem report describes the infant as having proximal shortening of all limbs, a large head with hydrocephalus, and symmetrical anomalies of the digits consisting of two middle digits only on each hand and a prehensile type of big toe with a wide gap and then two lateral digits on each foot. The heart, lungs, liver, spleen, and kidneys were all present and showed no malformation. The body was too macerated for chromosome analysis. No radiographs were taken, apart from a prenatal X-ray showing short fetal femur and a short humerus. The mother was seen for genetic counselling and was advised that the risk of recurrence was less than 1%. A second child, a normal boy, was born in 1972.
The first
of
a
"
"
The second case was a third son, born in March, 1975, who died at 1 hours. He was delivered by lower-segment caesarean section at 36 weeks of pregnancy because of falling maternal Harrison, G. G. Br. med. J. 1971, iii, 454. Maisel, H. R., Sessions, D. G., Miller, R. N. Ann. Otolar. 1973, 82, 729. 15. Britt, B. A. Anesth. Analg. 1972, 51, 841.
13. 14.
