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Diastrophic dwarfism and pregnancy
CASE REPORT
Case report
Diastrophic dwarfism and pregnancy Jean-Marc Ayoubi, Pierre-Simon Jouk, Jean-Claude Pons A 34–year-old woman was referred to the department of obstetrics in August, 1999 after having become pregnant for the second time. She first became pregnant in early 1998, but miscarried. She had diastrophic dwarfism, an autosomal recessive condition as a result of which she was 0·94 m tall, with a substantially deformed vertebral column, and restrictive pulmonary disease. At 25 years, her vital capacity (VC) was 1·4 L (0·42% predicted) and her forced expiratory volume one second (FEV1) 1·25 L (0·44% predicted), with almost no residual volume. She had wanted to become pregnant for a decade, despite being advised against it by every obstetrician and respiratory physician she had consulted. Her spouse was 1·88 m tall, and had a normal semen analysis karyotype. During the pregnancy she was seen every month by an obstetrician and a respiratory physician and monitored with spirograms and blood gas analyses at each visit. The pregnancy was normal until the 25th week of gestation, when her VC was 0·9 L and FEV1 0·88 L; blood gas analysis was normal. Ultrasound showed normal fetal growth and morphology. She developed dyspnoea at 26 weeks, and was admitted to hospital for monitoring and rest. She was given dexamethasone 12 mg weekly for the next four weeks to prevent respiartory distress syndrome in the baby. A caesarean section was done under general anaesthesia at 32 weeks 2 days because of the mother’s increasing respiratory difficulties. A girl weighing 1750 g was delivered with apgar scores of 5, 8, and 8. Both mother and child had an uncomplicated postnatal course. The baby went home at 4 weeks of age and was normal on examination at 6 months. Diastrophic dwarfism is a rare disease previously confused with achondroplasia.1 A mutation of the DTDST (diastrophic dysplasia sulphate transporter) gene located on chromosome 5q32–q33 impairs functioning of the cell membrane sulphate-chloride exchanger, thus leading to undersulphation of proteoglycans in the cartilage matrix. The condition is characterised by dwarfism (height less than 1·20 m), limb deformation, scoliosis, and a short trunk.2 The latter two characteristics can cause severe restrictive pulmonary disease and thus respiratory complications. This rare disease was first identified in 1960 by Lamy and Maroteaux,3 who found 11 cases described between 1910 and 1960. Since 1960, nearly 100 further cases have been reported. The condition is autosomal recessive in inheritance: the risk of being a healthy
Diastrophic dwarfism Cause and clinical characteristics A mutation of DTDST on chromosome 5q32–q33 transmitted by autosomal recessive inheritance: risk of transmission by heterozygote child <1/200. Characterised by dwarfism (height less than 1·20 m), limb deformation, scoliosis, and short trunk, which result in severe restrictive pulmonary disease and respiratory complications. Pregnancy management Frequent obstetric, respiratory, and ultrasound monitoring. Monthly spirograms and blood gas analyses. Amniocentesis to rule out fetal disease. Monitor fetal lung development and mother's respiratory function to select the best moment for delivery—balancing the risks of preterm delivery with the mother's breathing problems.
carrier (heterozygote) in the general population is less than 1/200. In our patient the baby is an obligate heterozygote. Systematic screening of the population is not advised because the risk is low and ultrasound diagnosis possible. Several reports of antenatal ultrasound diagnosis have all led to therapeutic terminations.4,5 The absence of information about pregnancies in patients with diastrophic dwarfism and the possibility of respiratory and obstetric complications initially led us to discourage the patient from becoming pregnant, but this very determined patient did not follow our advice. She was monitored closely for both obstetric, and respiratory complications and antenatal diagnosis ruled out any fetal disease. This case report shows that patients with diastrophic dwarfism, with heights of less than 1·00 m, can conceive and reproduce sucessfully. Their mechanical respiratory disease, like that caused by many other conditions, requires that their respiratory function be monitored regularly to select the best moment for delivery, by balancing the risks of preterm delivery with the mother’s breathing problems. The good outcome here should not diminish the risks to these patients and their fetuses. Honestly informing these women of the pitfalls and risks they are undertaking is always needed. We thank C Brambilla, C Chirossel, C Farah-Vilar, I Grefenstete, C Marey, and M Meddoun for their assistance.
References 1
Lancet 2001; 358: 1778
2
Departements of Gynécologie-Obstétrique (J-M Ayoubi MD, J-C Pons PhD) and Génétique (P-S Jouk PhD), University Hospital, Grenoble, France
3
Correspondence to: Dr Jean-Marc Ayoubi, Centre Hospitalier Universitaire, Département de Gynécologie Obstétrique BP 185 38042 Grenoble Cedex 09 France (e-mail: [email protected])
1778
4 5
Salle B, Picot C, Vauzelle JL, et al. Le nanisme diastrophique - à propos de trois observations chez le nouveau-né. Pediatrie 1966; 21: 311. Hastbacka J, de la Chapelle A, Mahtani MM, et al. The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine structure linkage disequilibrium mapping. Cell 1994; 78: 1073–87. Lamy M, Maroteaux P. Le nanisme diastrophique. Presse Méd 1960; 68: 1977–80. Mantagos S, Weiss RR, Mahoney M, Hobbins JC. Prenatal diagnosis of diastrophic dysplasia. Am J Obstet Gynecol 1981; 39: 111–13. Jung C, Sohn C, Sergi C. Case report prenatal diagnosis of dystrophic dysplasia by ultrasound at 21 weeks of gestation in a mother with massive obesity. Prenat Diagn 1998; 18: 378–83.
THE LANCET • Vol 358 • November 24, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Case report
Diastrophic dwarfism and pregnancy Jean-Marc Ayoubi, Pierre-Simon Jouk, Jean-Claude Pons A 34–year-old woman was referred to the department of obstetrics in August, 1999 after having become pregnant for the second time. She first became pregnant in early 1998, but miscarried. She had diastrophic dwarfism, an autosomal recessive condition as a result of which she was 0·94 m tall, with a substantially deformed vertebral column, and restrictive pulmonary disease. At 25 years, her vital capacity (VC) was 1·4 L (0·42% predicted) and her forced expiratory volume one second (FEV1) 1·25 L (0·44% predicted), with almost no residual volume. She had wanted to become pregnant for a decade, despite being advised against it by every obstetrician and respiratory physician she had consulted. Her spouse was 1·88 m tall, and had a normal semen analysis karyotype. During the pregnancy she was seen every month by an obstetrician and a respiratory physician and monitored with spirograms and blood gas analyses at each visit. The pregnancy was normal until the 25th week of gestation, when her VC was 0·9 L and FEV1 0·88 L; blood gas analysis was normal. Ultrasound showed normal fetal growth and morphology. She developed dyspnoea at 26 weeks, and was admitted to hospital for monitoring and rest. She was given dexamethasone 12 mg weekly for the next four weeks to prevent respiartory distress syndrome in the baby. A caesarean section was done under general anaesthesia at 32 weeks 2 days because of the mother’s increasing respiratory difficulties. A girl weighing 1750 g was delivered with apgar scores of 5, 8, and 8. Both mother and child had an uncomplicated postnatal course. The baby went home at 4 weeks of age and was normal on examination at 6 months. Diastrophic dwarfism is a rare disease previously confused with achondroplasia.1 A mutation of the DTDST (diastrophic dysplasia sulphate transporter) gene located on chromosome 5q32–q33 impairs functioning of the cell membrane sulphate-chloride exchanger, thus leading to undersulphation of proteoglycans in the cartilage matrix. The condition is characterised by dwarfism (height less than 1·20 m), limb deformation, scoliosis, and a short trunk.2 The latter two characteristics can cause severe restrictive pulmonary disease and thus respiratory complications. This rare disease was first identified in 1960 by Lamy and Maroteaux,3 who found 11 cases described between 1910 and 1960. Since 1960, nearly 100 further cases have been reported. The condition is autosomal recessive in inheritance: the risk of being a healthy
Diastrophic dwarfism Cause and clinical characteristics A mutation of DTDST on chromosome 5q32–q33 transmitted by autosomal recessive inheritance: risk of transmission by heterozygote child <1/200. Characterised by dwarfism (height less than 1·20 m), limb deformation, scoliosis, and short trunk, which result in severe restrictive pulmonary disease and respiratory complications. Pregnancy management Frequent obstetric, respiratory, and ultrasound monitoring. Monthly spirograms and blood gas analyses. Amniocentesis to rule out fetal disease. Monitor fetal lung development and mother's respiratory function to select the best moment for delivery—balancing the risks of preterm delivery with the mother's breathing problems.
carrier (heterozygote) in the general population is less than 1/200. In our patient the baby is an obligate heterozygote. Systematic screening of the population is not advised because the risk is low and ultrasound diagnosis possible. Several reports of antenatal ultrasound diagnosis have all led to therapeutic terminations.4,5 The absence of information about pregnancies in patients with diastrophic dwarfism and the possibility of respiratory and obstetric complications initially led us to discourage the patient from becoming pregnant, but this very determined patient did not follow our advice. She was monitored closely for both obstetric, and respiratory complications and antenatal diagnosis ruled out any fetal disease. This case report shows that patients with diastrophic dwarfism, with heights of less than 1·00 m, can conceive and reproduce sucessfully. Their mechanical respiratory disease, like that caused by many other conditions, requires that their respiratory function be monitored regularly to select the best moment for delivery, by balancing the risks of preterm delivery with the mother’s breathing problems. The good outcome here should not diminish the risks to these patients and their fetuses. Honestly informing these women of the pitfalls and risks they are undertaking is always needed. We thank C Brambilla, C Chirossel, C Farah-Vilar, I Grefenstete, C Marey, and M Meddoun for their assistance.
References 1
Lancet 2001; 358: 1778
2
Departements of Gynécologie-Obstétrique (J-M Ayoubi MD, J-C Pons PhD) and Génétique (P-S Jouk PhD), University Hospital, Grenoble, France
3
Correspondence to: Dr Jean-Marc Ayoubi, Centre Hospitalier Universitaire, Département de Gynécologie Obstétrique BP 185 38042 Grenoble Cedex 09 France (e-mail: [email protected])
1778
4 5
Salle B, Picot C, Vauzelle JL, et al. Le nanisme diastrophique - à propos de trois observations chez le nouveau-né. Pediatrie 1966; 21: 311. Hastbacka J, de la Chapelle A, Mahtani MM, et al. The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine structure linkage disequilibrium mapping. Cell 1994; 78: 1073–87. Lamy M, Maroteaux P. Le nanisme diastrophique. Presse Méd 1960; 68: 1977–80. Mantagos S, Weiss RR, Mahoney M, Hobbins JC. Prenatal diagnosis of diastrophic dysplasia. Am J Obstet Gynecol 1981; 39: 111–13. Jung C, Sohn C, Sergi C. Case report prenatal diagnosis of dystrophic dysplasia by ultrasound at 21 weeks of gestation in a mother with massive obesity. Prenat Diagn 1998; 18: 378–83.
THE LANCET • Vol 358 • November 24, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.