Volume 95 Number 3
Brief clinical and laboratory observations
463
Arthrogryposis multiplex congenita-prenatal assessment with diagnostic ultrasound and fetoscopy Murray Miskin, M.D., F.R.C.P.(C),* Randy Rothberg, M.D., F.R.C.P.(C), Noreen L. Rudd, M.D., F.R.C.P.(C), Ronald J. Benzie, M.B., Ch.B., M.R.C.G.P., M.R.C.O.G., F.R.C.S.(C), and Jerry Shime, M.D., F.R.C.S.(C), Toronto, Ont., Canada
A R T H R O G R Y P O S I S MULTIPLEX CONGENITA is a h e t e r o g e n e o u s g r o u p o f disorders characterized b y multiple congenital articular rigidities? W e recently h a d the o p p o r t u n i t y to study a case o f A M C in utero in a m o t h e r whose previous p r e g n a n c y was also affected with this condition. W e h a d h o p e d to be able to rule o u t the presence o f A M C before 20 weeks' gestation, u s i n g the diagnostic c o m b i n a t i o n o f fetoscopy a n d ultrasonography. However, this a t t e m p t was unsuccessful.
CASE REPORT The patient was a 23-year-old gravida 3, para 2 woman. In 1976 she delivered a mildly macerated stillborn fetus at 32 weeks' gestation. A postmortem was not carried out.
From the Departments of Radiology, Obstetrics and Gynecology, and Medical Genetics and Pediatrics, University of Toronto; Division of Diagnostic Ultrasound, Mount Sinai Hospital; Antenatal Genetic Clinic, Hospital for Sick Children; and Toronto General Hospital. *Reprint address: Departmentof Radiological Sciences, Mount Sinai Hospital, 600 UniversityA re., Toronto, Ontario MSG 1X3.
In February, 1977, the patient was admitted to the hospital during the thirty-fifth week of her second pregnancy. Fetal bradycardia developed and a cesarean section had to be performed. An 1,865 gm male infant was delivered alive, but died within a few minutes. The infant had micrognathia, high-arched palate, low-set ears, hypertel0rism, microstomia, cataract of the fight eye, and cryptorchidism. There was digitalization of the thumbs, and absent palmar creases. The feet were narrow. There were flexion contractures of elbows, wrists, hips, and knees. Abbreviations used AMC: arthrogryposis multiplex congenita BPD: biparietal diameter After the second pregnancy, the patient was seen at the Genetics Clinic at the Hospital for Sick Children. She was advised that if she undertook another pregnancy, there would be an increased chance of recurrence; exact risk figures were difficult to calculate since it was not clear whether the first pregnancy was also affected. In addition, it was explained that in a future pregnancy there would be no biochemical method of assessing the presence of AMC prenatally, but that fetoscopy or ultrasonography or both might be of some help.
Fig. 1. An ultrasonogram at 35weeks shows an upper extremitity-from shoulder to hand. Polyhydramnios is present. (It is most unusual to be able to see an entire limb on a compound contact scan. It maintained the same position and configuration throughout the study--see text.)
0022-3476/79/090463 + 02500.20/0 9 1979 The C. V. Mosby Co.
464
Brief clinical and laboratory observations
The Journal of Pediatrics September 1979
was flaccid and had severe flexion contractures of the arms and legs. Despite intubation, he died after 1 hour and 26 minutes. Postmortem examination revealed an external appearance identical to that of his brother. Dissection revealed no abnormalities except that the muscles, excluding the diaphragm, were extremely hypoplastic. Microscopically, the abnormal findings were confined to the spinal cord and skeletal muscles. "Drop out" of anterior horn cells was noted, especially in the lumbar region. The muscles showed findings suggestive of neurogenic atrophy. The postmortem findings on the second baby of this patient revealed microscopic findings almost identical to those in the third baby just described. DISCUSSION
Fig. 2. A radiograph made at 34 weeks shows long slender long bones which are undermineralized. The patient was next seen in th e Antenatal Genetics Clinic at the University of Toronto in January, 1978, at approximately 13 weeks in her third pregnancy. Echographic examination three weeks later, revealed a 16-week gestation (biparietal. diameter, 3.3 cm) with an anterior placenta. Fetoscopy was performed immediately afterward via a fundal approach. The fetal extremities were seen, moved, and looked normal. Ultrasonography two weeks later (BPD 3.8 cm 17.5 week size), including compound contact and real time scanning, showed normal movement of the extremities. Three subsequent ultrasound examinations, however, at 23, 28, an6 35 weeks (BPD--8.9 era) failed to show any fetal movement. The patient had developed polyhydramnios before the last examination and the fetus could therefore be seen very clearly. One of the upper extremities could be visualized in its entirety with the compound, Contact scanner. Despite prolonged observation with real time and even though the maternal abdomen was jostled several times by the examiner, the extremity maintained the configuration shown in Fig. 1, In fact, the whole extremity was seen to "tremble" as a unit as a fluid thrill produced by poking the maternal abdomen passed over it. The fetal heart was easily detectable. Except for one occasion during the pregnancy, the patient did not feel any fetal movement. Abdominal radiography performed at 34 weeks showed that the extremities were Iong, slender, and undermineralized (Fig. 2). The patient presented in early labor at 35 weeks. A repeat section was performed. A 1,570 gm male infant was delivered; he
Although A M C is usually sporadic in occurrence, several families have been recorded in w h o m multiple siblings have been affected. This fact raises the possibility of autosomal recessive inheritance. 2-~ W e had hoped to be able to decide before 20 weeks w h e t h e r or not the third pregnancy was affected, to afford the parents the option for termination. However, only from the observations at 23 weeks and afterward were we able to say that the pregnancy was indeed affected. It would seem, therefore, that the loss of anterior horn cells became sufficiently profound between 17 and 23 weeks to result in decreased to absent m o v e m e n t of the extremities. The contractures present at birth developed secondary to the neurologic impairment. It is not possible to know what degree of anterior horn cell development did occur in this fetus, but that there were functioning cells present is evident from the initial findings o f fetal m o v e m e n t before 20 weeks. This case illustrates that at least in the type o f A M C due to anterior horn cell loss, the diagnosis may not be possible before 20 weeks' gestation. There m a y be some fetuses with A M C whose anterior horn cell loss is so profound that absence of m o v e m e n t is not detectable even before 20 weeks. It would seem that the process is a degenerative one which becomes worse as the pregnancy progresses. The assistance of Lucinda Whitman, medical student, and the secretarial assistance of Christine Bobkowski are gratefully acknowledged. REFERENCES
1. Potter EL, and Craig JM: Pathology of the infant and fetus, Chicggo, 1975, Year Book Medical Publishers, Inc, pp. 620-621. 2. Shepard MK: Arthrogryposis multiplex congenita in sibs, Birth Defects 7:127, 1971. 3. Pena CE, Miller F, Budzelovick GN, and Feigin I. Arthrogryposis multiplex congenita-report of two cases of a radicular type with familial incidence, Neurology 18:926, 1968. 4. Mease AD: A syndrome of ankylosis, facial anomalies, pulmonary hypoplasia secondary to fetal neuromuscular dysfunction, Birth Defects 12:193, 1976.
Brief clinical and laboratory observations
463
Arthrogryposis multiplex congenita-prenatal assessment with diagnostic ultrasound and fetoscopy Murray Miskin, M.D., F.R.C.P.(C),* Randy Rothberg, M.D., F.R.C.P.(C), Noreen L. Rudd, M.D., F.R.C.P.(C), Ronald J. Benzie, M.B., Ch.B., M.R.C.G.P., M.R.C.O.G., F.R.C.S.(C), and Jerry Shime, M.D., F.R.C.S.(C), Toronto, Ont., Canada
A R T H R O G R Y P O S I S MULTIPLEX CONGENITA is a h e t e r o g e n e o u s g r o u p o f disorders characterized b y multiple congenital articular rigidities? W e recently h a d the o p p o r t u n i t y to study a case o f A M C in utero in a m o t h e r whose previous p r e g n a n c y was also affected with this condition. W e h a d h o p e d to be able to rule o u t the presence o f A M C before 20 weeks' gestation, u s i n g the diagnostic c o m b i n a t i o n o f fetoscopy a n d ultrasonography. However, this a t t e m p t was unsuccessful.
CASE REPORT The patient was a 23-year-old gravida 3, para 2 woman. In 1976 she delivered a mildly macerated stillborn fetus at 32 weeks' gestation. A postmortem was not carried out.
From the Departments of Radiology, Obstetrics and Gynecology, and Medical Genetics and Pediatrics, University of Toronto; Division of Diagnostic Ultrasound, Mount Sinai Hospital; Antenatal Genetic Clinic, Hospital for Sick Children; and Toronto General Hospital. *Reprint address: Departmentof Radiological Sciences, Mount Sinai Hospital, 600 UniversityA re., Toronto, Ontario MSG 1X3.
In February, 1977, the patient was admitted to the hospital during the thirty-fifth week of her second pregnancy. Fetal bradycardia developed and a cesarean section had to be performed. An 1,865 gm male infant was delivered alive, but died within a few minutes. The infant had micrognathia, high-arched palate, low-set ears, hypertel0rism, microstomia, cataract of the fight eye, and cryptorchidism. There was digitalization of the thumbs, and absent palmar creases. The feet were narrow. There were flexion contractures of elbows, wrists, hips, and knees. Abbreviations used AMC: arthrogryposis multiplex congenita BPD: biparietal diameter After the second pregnancy, the patient was seen at the Genetics Clinic at the Hospital for Sick Children. She was advised that if she undertook another pregnancy, there would be an increased chance of recurrence; exact risk figures were difficult to calculate since it was not clear whether the first pregnancy was also affected. In addition, it was explained that in a future pregnancy there would be no biochemical method of assessing the presence of AMC prenatally, but that fetoscopy or ultrasonography or both might be of some help.
Fig. 1. An ultrasonogram at 35weeks shows an upper extremitity-from shoulder to hand. Polyhydramnios is present. (It is most unusual to be able to see an entire limb on a compound contact scan. It maintained the same position and configuration throughout the study--see text.)
0022-3476/79/090463 + 02500.20/0 9 1979 The C. V. Mosby Co.
464
Brief clinical and laboratory observations
The Journal of Pediatrics September 1979
was flaccid and had severe flexion contractures of the arms and legs. Despite intubation, he died after 1 hour and 26 minutes. Postmortem examination revealed an external appearance identical to that of his brother. Dissection revealed no abnormalities except that the muscles, excluding the diaphragm, were extremely hypoplastic. Microscopically, the abnormal findings were confined to the spinal cord and skeletal muscles. "Drop out" of anterior horn cells was noted, especially in the lumbar region. The muscles showed findings suggestive of neurogenic atrophy. The postmortem findings on the second baby of this patient revealed microscopic findings almost identical to those in the third baby just described. DISCUSSION
Fig. 2. A radiograph made at 34 weeks shows long slender long bones which are undermineralized. The patient was next seen in th e Antenatal Genetics Clinic at the University of Toronto in January, 1978, at approximately 13 weeks in her third pregnancy. Echographic examination three weeks later, revealed a 16-week gestation (biparietal. diameter, 3.3 cm) with an anterior placenta. Fetoscopy was performed immediately afterward via a fundal approach. The fetal extremities were seen, moved, and looked normal. Ultrasonography two weeks later (BPD 3.8 cm 17.5 week size), including compound contact and real time scanning, showed normal movement of the extremities. Three subsequent ultrasound examinations, however, at 23, 28, an6 35 weeks (BPD--8.9 era) failed to show any fetal movement. The patient had developed polyhydramnios before the last examination and the fetus could therefore be seen very clearly. One of the upper extremities could be visualized in its entirety with the compound, Contact scanner. Despite prolonged observation with real time and even though the maternal abdomen was jostled several times by the examiner, the extremity maintained the configuration shown in Fig. 1, In fact, the whole extremity was seen to "tremble" as a unit as a fluid thrill produced by poking the maternal abdomen passed over it. The fetal heart was easily detectable. Except for one occasion during the pregnancy, the patient did not feel any fetal movement. Abdominal radiography performed at 34 weeks showed that the extremities were Iong, slender, and undermineralized (Fig. 2). The patient presented in early labor at 35 weeks. A repeat section was performed. A 1,570 gm male infant was delivered; he
Although A M C is usually sporadic in occurrence, several families have been recorded in w h o m multiple siblings have been affected. This fact raises the possibility of autosomal recessive inheritance. 2-~ W e had hoped to be able to decide before 20 weeks w h e t h e r or not the third pregnancy was affected, to afford the parents the option for termination. However, only from the observations at 23 weeks and afterward were we able to say that the pregnancy was indeed affected. It would seem, therefore, that the loss of anterior horn cells became sufficiently profound between 17 and 23 weeks to result in decreased to absent m o v e m e n t of the extremities. The contractures present at birth developed secondary to the neurologic impairment. It is not possible to know what degree of anterior horn cell development did occur in this fetus, but that there were functioning cells present is evident from the initial findings o f fetal m o v e m e n t before 20 weeks. This case illustrates that at least in the type o f A M C due to anterior horn cell loss, the diagnosis may not be possible before 20 weeks' gestation. There m a y be some fetuses with A M C whose anterior horn cell loss is so profound that absence of m o v e m e n t is not detectable even before 20 weeks. It would seem that the process is a degenerative one which becomes worse as the pregnancy progresses. The assistance of Lucinda Whitman, medical student, and the secretarial assistance of Christine Bobkowski are gratefully acknowledged. REFERENCES
1. Potter EL, and Craig JM: Pathology of the infant and fetus, Chicggo, 1975, Year Book Medical Publishers, Inc, pp. 620-621. 2. Shepard MK: Arthrogryposis multiplex congenita in sibs, Birth Defects 7:127, 1971. 3. Pena CE, Miller F, Budzelovick GN, and Feigin I. Arthrogryposis multiplex congenita-report of two cases of a radicular type with familial incidence, Neurology 18:926, 1968. 4. Mease AD: A syndrome of ankylosis, facial anomalies, pulmonary hypoplasia secondary to fetal neuromuscular dysfunction, Birth Defects 12:193, 1976.
