REFERENCES 1. Segawa M, Ohmi K, Ito S, Aoyama M, Hatakawa H. Childhood basal ganglia disease with remarkable response to L-dopa, hereditary basal ganglia disease with marked diurnal fluctuation (in Japanese). Shinryo (Tokyo) 1971;24:667-72. 2. Segawa M, Hosaka A, Miyajima F, et al. Hereditary progressive dystonia with marked diurnal fluctuation. In: Eldridge R, Fahn S, eds. Dystonia. Advances in Neurology. Vol 14. New York: Raven Press, 1976:215-33. 3. Ouvrier RA. Progressive dystonia with marked diurnal fluctuation. Ann NeuroI1987;4:412-7. 4. Deonna T. Dopa responsible progressive dystonia of childhood with fluctuations of symptoms-Segawa's syndrome and possible variants. Neuropediatrics 1986; 17:75-80. 5. Yokochi M, Narabayashi H, Iizuka R, Nagatsu T. Juvenile parkinsonism: some clinical, pharmacological, and neuropathological aspects. In: Haasler RG, Christ JF, eds. Par· kinson·specific motor and mental disorders. Advances in Neurology. Vol 40. New York: Raven Press, 1984:407-13.
6. Yamamura Y, Sobue I, Ando K, et al. Paralysis agitans of early onset with marked diurnal fluctuation of symptoms. Neurology (Minneap) 1973;23:239-44. 7. Sunuhara N, Mano Y, Ando K, Satoyoshi E. Idiopathic dystonia-Pakinsonism with marked diurnal fluctuation of symptoms. Ann Neurol 1985; 17:39-45. 8. Segawa M, Nomura Y, Tanaka S, et al. Hereditary progressive dystonia with marked diurnal fluctuation-consideration on its pathophysiology based on the characteristics of clinical and polysomnographical findings. In: Fahn S, ed. Dystonia II Advances in Neurology. Vol 50. New York: Raven Press, 1988 :367-76. 9. Kaufman S, Berlow S, Summer GK, et al. Hyperphenylalaninemia due to a deficiency of biopterin; a variant form of phenylketonuria. N Engl J Med 1978; 299:673-9. 10. Fink JK, Barton N, Cohen W, et al. Dystonia with marked diurnal variation associated with biopterin deficiency. Ne~ro· logy 1988;38:707-11.
Congenital Myotonic Dystrophy with Progressive Edema and Hypoproteinemia Tatsuya Fujii, MD, Tohru Y orifuji, MD, Takehiko Okuno, MD, Shinya Toyokuni, MD, Shigeru Okada, MD and Haruki Mikawa, MD
We report a patient with congenital myotonic dystrophy who had progressive edema and hypoproteinemia. An atrioseptal defect and patent ductus arteriosus were noted and were considered to be the cause of the right heart failure and edema. Although urinary protein levels were minimal, infusion of albumin did not improve the hypoproteinemia. Administration of dexamethasone increased the serum protein level, but the edema was not ameliorated. Autopsy revealed a slight lymphatic dilatation in the small intestine, suggesting protein-losing enteropathy. Key words: Congenital myotonic dystrophy, edema, hypoproteinemia, heart failure, and protein·losing enteropathy. Fujii T, Yorifuji T, Okuno T, Toyokuni S, Okada S, Mikawa H. Congenital myotonic dystrophy with progressive edema and hypoproteinemia. BrainDev 1991;13:58-60
From the Departments of Pediatrics [TF, TY, TO, HM], and Pathology [ST], Kyoto University, Faculty of Medicine, Kyoto; and Department of Pathology, Okayama University School of Medicine [SO), Okayama. Received for publication: June 28,1990. Accepted for publication: January 21, 1991. Correspondence address: Dr. Tatsuya Fujii, Department of Pediatrics, Kyoto University, Faculty of Medicine, Shogoin, Sakyo, Kyoto 606, Japan.
Most babies with congenital myotonic dystrophy (CMD) are born from a mother with myotonic dystrophy [1]. The disease is manifested with polyhydramnios, hypotonia, facial diplegia with tent-shaped mouth, hyporeflexia and talipes equinovarus [2,3]. Cerebral ventricular dilation is occasionally noted [4, 5], and chest X-ray shows elevated diaphragm and thin ribs [2,6]. Some patients have been reported to develop edema, but it disappears spontaneously in most cases [3,6,7]. We report a patient with CMD who developed progressive edema.
CASE REPORT The mother of this patient was 30 years old and had experienced stillbirth twice and spontaneous abortion once. Her family history was not remarkable. During the present pregnancy, increased serum creatine kinase levels, cataract, atrioventricular conduction block and myotonia were revealed, and she was diagnosed to have myotonic dystrophy. Since she developed polyhydramnios, delivery of the baby with CMD was anticipated. A baby girl was delivered by caesarean section after 37 weeks gestation. Birth weight was 2,634 gm. Apgar score was 3 at 1 min, and the baby was resuscitated by endotracheal intubation. Apgar score at 5 min was 6. The patient was transferred to our department immediately. Physical examination on admission revealed marked hypotonia, facial diplegia, and bilateral talipes equinovarus. Distal muscles of the legs were slightly atrophic and mild edema was noted in the extremities. Deep tendon reflexes
AUTOPSY FINDINGS
Fig 1 The patient shortly after death. Prominent generalized edema and deformity of the bilateral ankle joints are noted.
.. • ~.
, " "
' -'~
were slightly below normal. Electromyography revealed no myotonic discharges. A respirator was necessary to maintain adequate ventilation, and chest X-ray showed raised right hemidiaphragm and thin ribs. Ultrasound scan of the brain on day 3 revealed ventricular dilation, but no evidence of intracranial hemorrhage was noted. Heart murmur was noted on day 5, and echocardiography revealed atrioseptal defect and patent ductus arteriosus. The serum level of total protein on admission was 3.4 mg/dl, and urinary protein level assessed by reagent strips was found to be negligible. One gm/kg of albumin was infused everyday, but the total serum protein level on day 4 remained low (4.2 mg/dl), and the edema became prominent in head and extremities. Urinalysis again showed a trace amount of protein. Serum level of IgG was 159.8 mg/dl, and IgA and IgM were undetectable. The white blood cell count was 7,100/mm 3 with the lymphocytes 1,207/mm 3 (normal, 2,000-17,000). Doses of albumin were increased to 2 to 3 gm/kg/day and total protein levels were maintained at from 4.4 to 4.8 mg/kg. Because of the marked edema and persistent hypoproteinemia of unknown cause, dexamethasone was administered at a dose of 0.5 mg/kg/day for seven days and at gradually lowered doses for three more days. With this treatment, the serum level of total protein was increased to 5.3 to 5.5 mg/dl, and IgG increased to 447.7 mg/dl. However, the edema did not improve. Withdrawal of the steroid decreased the serum protein level again. Serum creatinine levels, which were normal on the first day, began to increase from day 12, and a tendency for bleeding with disseminated intravascular coagUlation became obvious at three weeks. The patient died on day 33. Chromosome analysis was not done.
:,
Fig 2 Autopsied tongue muscle shows loosely arranged, small, round jibers, and the vesicular internal nuclei. Hematoxylin·eosin stain. x 400.
Marked generalized edema and talipes equinovarus were noted (Fig 1). Skeletal muscles in the tongue, diaphragm, psoas and quadriceps femoris muscles were atrophic and pale in color. They showed many features of immaturity, such as small, rounded muscle fibers, vesicular internal nuclei and chained nuclei (Fig 2). Multiple muscle spindles with thickened capsules were revealed. Histochemical stains for myofibrillar ATPase at pH 9.4 demonstrated a small proportion of dark-staining fibers. At pH 4.4 the fibers were uniformly light staining. NADH-tetrazolium reductase stains failed to demonstrate a differentiation into various muscle fiber types, and a light peripheral halo was not observed. An atrioseptal defect, 6 mm in diameter, was revealed in the heart, and ductus arteriosus, 4 mm in diameter, was noted. The liver showed congestion in the acinar zones 2 to 3, fatty changes in hepatocytes and centrilobular fibrosis. Congestion was also noted in the kidney, spleen and intestines. Renal glomeruli showed an immaturity which is consistent with the developmental
Fujii et al: Congenital myotonic dystrophy 59
age. Moderate gastrointestinal bleeding due to erosion throughout the alimentary tract was observed. Slight lymphatic dilation was noted in the small intestine. The brain showed ventricular dilation without aqueductal stenosis. Subarachnoid hemorrhage was noted in the right temporal lobe and bilaterally in the cerebellum, but no hemorrhage was revealed in the brain parenchyma and in the ventricle. DISCUSSION Congenital lymphedema is known to develop in babies with the Turner syndrome r8]. Although chromosome analysis was not done, our patient did not have characteristic fmdings indicative of the Turner syndrome, and the clinical symptoms and muscle autopsy fmdings which showed immature fibers in this patient were compatible with CMD [9]. Farkas et al [10] reported the presence of a peripheral halo in the muscle biopsy specimens from 3 patients with CMD, which was absent in our patient. However, the halo was also noted in patients with hypotonia due to other neuromuscular disorders, indicating that it is not specific to CMD [111, thus the diagnosis of CMD is essentially based on clinical findings [7]. NeuenJacob et al [3] described edema as one of the characteristic fmdings seen in CMD. However, to our knowledge, no patients have ever been reported to have progressive severe edema. Several explanations for the cause of edema could be made in our patient: i) hypoproteinemia; ii) right heart failure due to patent ductus arteriosus and atrioseptal defect; and iii) renal hypofunction due to the immature glomeruli. An increase in the serum protein level with steroid treatment did not improve the edema. Therefore, hypoproteinemia could not explain the edema. Congestion in the acinar zones 2 to 3, and centrilobular fibrosis in the liver are the characteristic findings of the right heart failure [12]. Congestion of the other organs also suggested the presence of the heart failure, which may cause of the edema. Pearse & Howeler [7] speculated that output were normal at the onset of the edema, so the immaturity of the renal glomeruli found is an unlikely cause of the edema. Pearse & H6weler [7] speculated tha1 edema is caused by a reduction in lymphatic return from the periphery due to reduced fetal movement. However, this cannot explain the rapid progression of the edema after birth. Thus, we speculate that heart failure was the most likely cause of the progressive edema in our patient. The cause of hypoproteinemia is not known. Since urinary protein levels were minimal at the beginning, urinary loss of protein did not explain the hypoproteinemia. On the other hand, a fairly large amount of albumin infusion did not increase the serum protein levels, indicating an exaggerated loss of protein rather than decreased
60 Brain & Development, Vol 13, No 1, 1991
protein production. Increase in the serum protein level with steroid treatment suggested that the permeability of vessels or lymphatics to protein had been impaired, and was improved by the steroid. Protein-losing enteropathy has been reported to develop in patients with congestive heart failure [13, 14]. The presence of dilation of the lymphatics in the small intestine, decreased serum level of immunoglobulin, and lymphocytopenia in our patient indicate the possibility of this complication. However, the fact that the hypoproteinemia was noted at birth, and that the lymphatic dilation was mild may not support this possibility. Since we could not examine the protein turnover, whether the patient had protein-losing enteropathy or not is unknown. REFERENCES 1. Harper PS, Dyken PR. Early-onset dystrophia myotonica: evidence supporting a maternal environmental factor. Lancet 1972;2: 53-5. 2. Cunningham A, Procopis PG. Neonatal myotonic dystrophy. Aust Paediatr J 1988;24 (suppl1): 74-6. 3. Neuen-Jacob E, Voit TH, Turski J, Lenard HG, Wechsler W. Neonatal myotonic dystrophy in a premature infant: clinical and morphological fmdings. Gin Neuropathol 1987;6: 236-40. 4. Fox GN, Gravett MG. Neonatal myotonic dystrophy associated with prenatal ventriculomegaly: a case report. J Reprod Med 1986;31: 729-31. 5. Regev R, de Vries LS, Heckmatt JZ, Dubowitz V. Cerebral ventricular dilation in congenital myotonic dystrophy. J Pediatr 1987; 111 :372-6. 6. Wesstrom G, Bensch J, Schollin J. Congenital myotonic dystrophy: incedence, clinical aspects and early prognosis. Acta Paediatr Scand 1986; 75 :849-54. 7. Pearse RG, Howeler CJ. Neonatal form of dystrophia myotonica: five cases in pre term babies and a review of earlier reports. Arch Dis Child 1979;54:331-8. 8. Jones KL. Smith's recognizable patterns of human malformation. Philadelphia· London· Toronto·Montreal·Sydney· Tokyo: W.B. Saunders Company, Harcourt Brace Jovanovich Inc, 1988:74-5. 9. Sarnat HB, Silbert SW. Maturational arrest of fetal muscle in neonatal myotonic dystrophy: a pathological study of four cases. Arch NeuroI1976;33:466-74. 10. Farkas E, Tome FMS, Fardeau M, Arsenio-Nunes ML, Dreyfus P, Diebler MF. Histochemical and ultrastructural study of muscle biopsies in 3 cases of dystrophia myotonica in the newborn child. J Neurol Sci 1974;21:273-88. 11. Farkas-Bargeton E, Aicardi J, Arsenio-Nunes ML, Wehrle R. Delay in the maturation of muscle fibers in infants with congenital hypotonia. J Neurol Sci 1978;39:17-29. 12. Bras G, Brandt KH. Vascular disorders. In: MacSween RNM, Anthony PP, Scheuer PJ, eds. Pathology of the liver. Edinburgh· London· Melbourne· New York: Churchill Livingstone, 1987:478-502. ' 13. Davidson JD, Waldmann TA, Goodman DS, Gordon RS JI. Protein-losing gastroenteropathy in congenital heart-failure. Lancet 1961; 1:899-902. 14. Jeejeebhoy KN. Cause of hypoalbuminemia in patients with gastrointestinal and cardiac disease. Lancet 1962; 1:343-8.
6. Yamamura Y, Sobue I, Ando K, et al. Paralysis agitans of early onset with marked diurnal fluctuation of symptoms. Neurology (Minneap) 1973;23:239-44. 7. Sunuhara N, Mano Y, Ando K, Satoyoshi E. Idiopathic dystonia-Pakinsonism with marked diurnal fluctuation of symptoms. Ann Neurol 1985; 17:39-45. 8. Segawa M, Nomura Y, Tanaka S, et al. Hereditary progressive dystonia with marked diurnal fluctuation-consideration on its pathophysiology based on the characteristics of clinical and polysomnographical findings. In: Fahn S, ed. Dystonia II Advances in Neurology. Vol 50. New York: Raven Press, 1988 :367-76. 9. Kaufman S, Berlow S, Summer GK, et al. Hyperphenylalaninemia due to a deficiency of biopterin; a variant form of phenylketonuria. N Engl J Med 1978; 299:673-9. 10. Fink JK, Barton N, Cohen W, et al. Dystonia with marked diurnal variation associated with biopterin deficiency. Ne~ro· logy 1988;38:707-11.
Congenital Myotonic Dystrophy with Progressive Edema and Hypoproteinemia Tatsuya Fujii, MD, Tohru Y orifuji, MD, Takehiko Okuno, MD, Shinya Toyokuni, MD, Shigeru Okada, MD and Haruki Mikawa, MD
We report a patient with congenital myotonic dystrophy who had progressive edema and hypoproteinemia. An atrioseptal defect and patent ductus arteriosus were noted and were considered to be the cause of the right heart failure and edema. Although urinary protein levels were minimal, infusion of albumin did not improve the hypoproteinemia. Administration of dexamethasone increased the serum protein level, but the edema was not ameliorated. Autopsy revealed a slight lymphatic dilatation in the small intestine, suggesting protein-losing enteropathy. Key words: Congenital myotonic dystrophy, edema, hypoproteinemia, heart failure, and protein·losing enteropathy. Fujii T, Yorifuji T, Okuno T, Toyokuni S, Okada S, Mikawa H. Congenital myotonic dystrophy with progressive edema and hypoproteinemia. BrainDev 1991;13:58-60
From the Departments of Pediatrics [TF, TY, TO, HM], and Pathology [ST], Kyoto University, Faculty of Medicine, Kyoto; and Department of Pathology, Okayama University School of Medicine [SO), Okayama. Received for publication: June 28,1990. Accepted for publication: January 21, 1991. Correspondence address: Dr. Tatsuya Fujii, Department of Pediatrics, Kyoto University, Faculty of Medicine, Shogoin, Sakyo, Kyoto 606, Japan.
Most babies with congenital myotonic dystrophy (CMD) are born from a mother with myotonic dystrophy [1]. The disease is manifested with polyhydramnios, hypotonia, facial diplegia with tent-shaped mouth, hyporeflexia and talipes equinovarus [2,3]. Cerebral ventricular dilation is occasionally noted [4, 5], and chest X-ray shows elevated diaphragm and thin ribs [2,6]. Some patients have been reported to develop edema, but it disappears spontaneously in most cases [3,6,7]. We report a patient with CMD who developed progressive edema.
CASE REPORT The mother of this patient was 30 years old and had experienced stillbirth twice and spontaneous abortion once. Her family history was not remarkable. During the present pregnancy, increased serum creatine kinase levels, cataract, atrioventricular conduction block and myotonia were revealed, and she was diagnosed to have myotonic dystrophy. Since she developed polyhydramnios, delivery of the baby with CMD was anticipated. A baby girl was delivered by caesarean section after 37 weeks gestation. Birth weight was 2,634 gm. Apgar score was 3 at 1 min, and the baby was resuscitated by endotracheal intubation. Apgar score at 5 min was 6. The patient was transferred to our department immediately. Physical examination on admission revealed marked hypotonia, facial diplegia, and bilateral talipes equinovarus. Distal muscles of the legs were slightly atrophic and mild edema was noted in the extremities. Deep tendon reflexes
AUTOPSY FINDINGS
Fig 1 The patient shortly after death. Prominent generalized edema and deformity of the bilateral ankle joints are noted.
.. • ~.
, " "
' -'~
were slightly below normal. Electromyography revealed no myotonic discharges. A respirator was necessary to maintain adequate ventilation, and chest X-ray showed raised right hemidiaphragm and thin ribs. Ultrasound scan of the brain on day 3 revealed ventricular dilation, but no evidence of intracranial hemorrhage was noted. Heart murmur was noted on day 5, and echocardiography revealed atrioseptal defect and patent ductus arteriosus. The serum level of total protein on admission was 3.4 mg/dl, and urinary protein level assessed by reagent strips was found to be negligible. One gm/kg of albumin was infused everyday, but the total serum protein level on day 4 remained low (4.2 mg/dl), and the edema became prominent in head and extremities. Urinalysis again showed a trace amount of protein. Serum level of IgG was 159.8 mg/dl, and IgA and IgM were undetectable. The white blood cell count was 7,100/mm 3 with the lymphocytes 1,207/mm 3 (normal, 2,000-17,000). Doses of albumin were increased to 2 to 3 gm/kg/day and total protein levels were maintained at from 4.4 to 4.8 mg/kg. Because of the marked edema and persistent hypoproteinemia of unknown cause, dexamethasone was administered at a dose of 0.5 mg/kg/day for seven days and at gradually lowered doses for three more days. With this treatment, the serum level of total protein was increased to 5.3 to 5.5 mg/dl, and IgG increased to 447.7 mg/dl. However, the edema did not improve. Withdrawal of the steroid decreased the serum protein level again. Serum creatinine levels, which were normal on the first day, began to increase from day 12, and a tendency for bleeding with disseminated intravascular coagUlation became obvious at three weeks. The patient died on day 33. Chromosome analysis was not done.
:,
Fig 2 Autopsied tongue muscle shows loosely arranged, small, round jibers, and the vesicular internal nuclei. Hematoxylin·eosin stain. x 400.
Marked generalized edema and talipes equinovarus were noted (Fig 1). Skeletal muscles in the tongue, diaphragm, psoas and quadriceps femoris muscles were atrophic and pale in color. They showed many features of immaturity, such as small, rounded muscle fibers, vesicular internal nuclei and chained nuclei (Fig 2). Multiple muscle spindles with thickened capsules were revealed. Histochemical stains for myofibrillar ATPase at pH 9.4 demonstrated a small proportion of dark-staining fibers. At pH 4.4 the fibers were uniformly light staining. NADH-tetrazolium reductase stains failed to demonstrate a differentiation into various muscle fiber types, and a light peripheral halo was not observed. An atrioseptal defect, 6 mm in diameter, was revealed in the heart, and ductus arteriosus, 4 mm in diameter, was noted. The liver showed congestion in the acinar zones 2 to 3, fatty changes in hepatocytes and centrilobular fibrosis. Congestion was also noted in the kidney, spleen and intestines. Renal glomeruli showed an immaturity which is consistent with the developmental
Fujii et al: Congenital myotonic dystrophy 59
age. Moderate gastrointestinal bleeding due to erosion throughout the alimentary tract was observed. Slight lymphatic dilation was noted in the small intestine. The brain showed ventricular dilation without aqueductal stenosis. Subarachnoid hemorrhage was noted in the right temporal lobe and bilaterally in the cerebellum, but no hemorrhage was revealed in the brain parenchyma and in the ventricle. DISCUSSION Congenital lymphedema is known to develop in babies with the Turner syndrome r8]. Although chromosome analysis was not done, our patient did not have characteristic fmdings indicative of the Turner syndrome, and the clinical symptoms and muscle autopsy fmdings which showed immature fibers in this patient were compatible with CMD [9]. Farkas et al [10] reported the presence of a peripheral halo in the muscle biopsy specimens from 3 patients with CMD, which was absent in our patient. However, the halo was also noted in patients with hypotonia due to other neuromuscular disorders, indicating that it is not specific to CMD [111, thus the diagnosis of CMD is essentially based on clinical findings [7]. NeuenJacob et al [3] described edema as one of the characteristic fmdings seen in CMD. However, to our knowledge, no patients have ever been reported to have progressive severe edema. Several explanations for the cause of edema could be made in our patient: i) hypoproteinemia; ii) right heart failure due to patent ductus arteriosus and atrioseptal defect; and iii) renal hypofunction due to the immature glomeruli. An increase in the serum protein level with steroid treatment did not improve the edema. Therefore, hypoproteinemia could not explain the edema. Congestion in the acinar zones 2 to 3, and centrilobular fibrosis in the liver are the characteristic findings of the right heart failure [12]. Congestion of the other organs also suggested the presence of the heart failure, which may cause of the edema. Pearse & Howeler [7] speculated that output were normal at the onset of the edema, so the immaturity of the renal glomeruli found is an unlikely cause of the edema. Pearse & H6weler [7] speculated tha1 edema is caused by a reduction in lymphatic return from the periphery due to reduced fetal movement. However, this cannot explain the rapid progression of the edema after birth. Thus, we speculate that heart failure was the most likely cause of the progressive edema in our patient. The cause of hypoproteinemia is not known. Since urinary protein levels were minimal at the beginning, urinary loss of protein did not explain the hypoproteinemia. On the other hand, a fairly large amount of albumin infusion did not increase the serum protein levels, indicating an exaggerated loss of protein rather than decreased
60 Brain & Development, Vol 13, No 1, 1991
protein production. Increase in the serum protein level with steroid treatment suggested that the permeability of vessels or lymphatics to protein had been impaired, and was improved by the steroid. Protein-losing enteropathy has been reported to develop in patients with congestive heart failure [13, 14]. The presence of dilation of the lymphatics in the small intestine, decreased serum level of immunoglobulin, and lymphocytopenia in our patient indicate the possibility of this complication. However, the fact that the hypoproteinemia was noted at birth, and that the lymphatic dilation was mild may not support this possibility. Since we could not examine the protein turnover, whether the patient had protein-losing enteropathy or not is unknown. REFERENCES 1. Harper PS, Dyken PR. Early-onset dystrophia myotonica: evidence supporting a maternal environmental factor. Lancet 1972;2: 53-5. 2. Cunningham A, Procopis PG. Neonatal myotonic dystrophy. Aust Paediatr J 1988;24 (suppl1): 74-6. 3. Neuen-Jacob E, Voit TH, Turski J, Lenard HG, Wechsler W. Neonatal myotonic dystrophy in a premature infant: clinical and morphological fmdings. Gin Neuropathol 1987;6: 236-40. 4. Fox GN, Gravett MG. Neonatal myotonic dystrophy associated with prenatal ventriculomegaly: a case report. J Reprod Med 1986;31: 729-31. 5. Regev R, de Vries LS, Heckmatt JZ, Dubowitz V. Cerebral ventricular dilation in congenital myotonic dystrophy. J Pediatr 1987; 111 :372-6. 6. Wesstrom G, Bensch J, Schollin J. Congenital myotonic dystrophy: incedence, clinical aspects and early prognosis. Acta Paediatr Scand 1986; 75 :849-54. 7. Pearse RG, Howeler CJ. Neonatal form of dystrophia myotonica: five cases in pre term babies and a review of earlier reports. Arch Dis Child 1979;54:331-8. 8. Jones KL. Smith's recognizable patterns of human malformation. Philadelphia· London· Toronto·Montreal·Sydney· Tokyo: W.B. Saunders Company, Harcourt Brace Jovanovich Inc, 1988:74-5. 9. Sarnat HB, Silbert SW. Maturational arrest of fetal muscle in neonatal myotonic dystrophy: a pathological study of four cases. Arch NeuroI1976;33:466-74. 10. Farkas E, Tome FMS, Fardeau M, Arsenio-Nunes ML, Dreyfus P, Diebler MF. Histochemical and ultrastructural study of muscle biopsies in 3 cases of dystrophia myotonica in the newborn child. J Neurol Sci 1974;21:273-88. 11. Farkas-Bargeton E, Aicardi J, Arsenio-Nunes ML, Wehrle R. Delay in the maturation of muscle fibers in infants with congenital hypotonia. J Neurol Sci 1978;39:17-29. 12. Bras G, Brandt KH. Vascular disorders. In: MacSween RNM, Anthony PP, Scheuer PJ, eds. Pathology of the liver. Edinburgh· London· Melbourne· New York: Churchill Livingstone, 1987:478-502. ' 13. Davidson JD, Waldmann TA, Goodman DS, Gordon RS JI. Protein-losing gastroenteropathy in congenital heart-failure. Lancet 1961; 1:899-902. 14. Jeejeebhoy KN. Cause of hypoalbuminemia in patients with gastrointestinal and cardiac disease. Lancet 1962; 1:343-8.
