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Occlusive hydrocephalus in congenital myotonic dystrophy
Brain & Development 23 (2001) 122±124
www.elsevier.com/locate/braindev
Case report
Occlusive hydrocephalus in congenital myotonic dystrophy Werner Rettwitz-Volk a,1,*, Mats Wikstroem b, Olof Flodmark c a
Pediatric Clinic, Krankenhaus Friedrichshafen, Germany Department of Radiology, Krankenhaus Friedrichshafen, Germany c Department of Neuroradiology, Karolinska Institute, Stockholm, Sweden b
Received 3 July 2000; received in revised form 11 December 2000; accepted 15 December 2000
Abstract A case of congenital myotonic dystrophy is reported which was complicated by the development of a hydrocephalus that needed ventricular-peritoneal shunting at the age of 4 months. Although dilatation of cerebral ventricles is a common feature in these patients, an occlusive hydrocephalus has not so far been reported. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Congenital myotonic dystrophy; Hydrocephalus
1. Introduction Congenital myotonic dystrophy represents the neonatal variant of Curschmann±Steinert myotonia and is an autosomal dominantly inherited condition with an incidence estimated to be 13/100 000 liveborns [1]. In general, the disease is transmitted by the mother although paternal transmission has been reported [2]. The molecular basis is an unstable DNA fragment consisting of a variable expansion of a CTG triplet at the 3 0 end of the gene encoding myotonin protein kinase which is localised on chromosome 19 (19q 13.2± 13.3) [3]. The severity of the disease is directly correlated to the length of the CTG sequence [4]. Affected newborns can present with intrauterine growth retardation, prematurity, birth asphyxia, respiratory distress often requiring mechanical ventilation [5] and always exhibit generalised muscular hypotonia [5]. Feeding problems are common [5] and an association with protein losing enteropathy [6], hydrops fetalis [7], and persistent pulmonary hypertension of the newborn [8] has been described. The initial muscular hypotonia usually improves so that the patients are able to walk with delay, but hypotonia tends to recur and myotonia ensues [1]. Twenty-®ve percent of the affected infants die within the ®rst 18 months of life, mainly during the neonatal period; half of the patients with Curschmann±Steinert myotonia reach their mid-30 s [9]. Most of * Corresponding author. Klinik fuÈr Kinder und Jugendliche, StaÈdtisches Krankenhaus Friedrichshafen Postfach 2360, D-88013 Friedrichshafen, Germany. Tel.: 149-75-4196-1450; fax: 149-75-4196-1266. 1 W. Rettwitz-Volk, BuÈrgerhospital Frankfurt, Nibelungenalle 37-41, D60318, Frankfurt, Germany.
them are severely mentally retarded with an IQ of 70 or less [10]. Muscle biopsy reveals only non-speci®c changes such as a selective atrophy of type 1 or type 2 muscle ®bers or no changes at all [11,12]. EMG and muscle enzymes are uninformative [12]. Imaging studies in patients with Curschmann±Steinert myotonia show ventriculomegaly [13,14,15], white matter lesions [13], hypoplastic corpus callosum [13], lesions of the cerebellum [13], macrocephaly [14], and periventricular hyperdensities [14]. Histological examination in some cases revealed neuronal migrational disturbance [14]. Although ventricular enlargement is a common feature in Curschmann±Steinert myotonia, increased intraventricular pressure requiring ventricular shunting has hitherto not been described. 2. Case report Our patient was the ®rst child of a 30-year-old primigravida/para. Pregnancy was uneventful and the infant was delivered at term by emergency caesarean section because of fetal bradycardia. One minute APGAR score was 3, arterial cord blood pH was 7.09, birth weight was 3250 g, and head circumference 37 cm (1 cm above 97th centile). As the girl showed no spontaneous breathing she was intubated and mechanical ventilation initiated. There was no need for supplemental oxygen and the main clinical feature was a marked muscular hypotonia and a tented upper lip was noted. On the 4th day of life the infant could be extubated although breathing dif®culties due to the muscular weakness persisted. As the clinical presentation suggested a congenital
0387-7604/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S03 87-7604(01)0017 6-0
W. Rettwitz-Volk et al. / Brain & Development 23 (2001) 122±124
myotonic dystrophy, strengthened by the typical symptoms of myotonia in the mother who was unaware of her condition until this very moment, further investigations were initiated. Molecular genetic studies revealed an expansion of a CTG triplet to 7 kb in the infant and to 0.8 kb in the mother. The defect was located in the myotonic dystrophy kinase gene in one allele with a normal second allele. Initial cranial ultrasound showed a mild enlargement of the lateral ventricles with a widening of the interhemispheric ®ssure (Fig. 1) and on the 15th day of life a marked cerebral ventriculomegaly as the only pathological ®nding could be seen. Intracranial perfusion remained undisturbed as could be shown by Doppler ultrasound. These ®ndings remained unchanged until discharge on day 35 when generalized muscular hypotonia was the main clinical feature. Subsequent monitoring showed a slowly progressive internal hydrocephalus without signs of increased intracranial pressure. From the age of about 11 weeks a rapidly increasing macrocephaly was noted and at the age of 14 weeks the girl presented with vomiting, lethargy and a tense anterior fontanelle. Head circumference was 48 cm (5.5 cm above 97th centile) at that time. CT scan showed a decompensating hydrocephalus (Fig. 2) and a permanent ventricular shunting was carried out. Additionally an asymmetrically enlarged cisterna magna could be seen (Fig. 3). After an uneventful further course the patient was discharged 4 weeks later. Subsequent cranial ultrasound scans revealed a mild ventricular enlargement with a normal perfusion as shown by Doppler ultrasound. At the last presentation at the age of 16 months, a marked muscular hypotonia was still apparent with psychomotor delay and a well functioning ventricularperitoneal shunt. 3. Discussion Ventricular enlargement is the most common neuropathological ®nding in Curschmann±Steinert myotonia. GarciaAlix et al. [14] found ventricular dilatation in 11 of 14
Fig. 1. Cranial ultrasound on the 2nd day of life. Mild ventricular enlargement and widening of the interhemispheric ®ssure.
123
Fig. 2. CT scan on week 14. Decompensating internal hydrocephalus.
affected infants as diagnosed by cranial ultrasound. Four infants showed a widening of the interhemispheric ®ssure as well and macrocephaly was noted in ten infants. There was no clinical sign of increased intracranial pressure. Tanabe et al. [15] saw ventricular dilatation in three of seven patients with Curschmann±Steinert myotonia and the condition did not progress in follow-up evaluation from 1 to 6 years. Hageman and co-workers [5] described nine cases of ventriculomegaly in their 13 patients and Hashimoto et al. [13] found not only enlargement of the lateral ventricles in all of their reported patients with Curschmann±Steinert myotonia but also enlargement of the third and fourth ventricles. The reason for this condition is not quite clear. In some cases an intraventricular hemorrhage preceded the hydrocephalus [16] while in others a cerebral dysgenesis was suspected [1] and a neuronal migrational disturbance was seen [14]. Neither in autopsied cases nor from clinical observations has a case of hydrocephalus with increased intracranial pressure been so far reported.
Fig. 3. CT scan on week 14. Asymmetrical enlargement of the cisterna magna with a reduced left cerebellar hemisphere.
124
W. Rettwitz-Volk et al. / Brain & Development 23 (2001) 122±124
The reason for the development of a hydrocephalus in our patient remains unclear. The sonographic examination on the 1st day of life showed a widening of the interhemispheric ®ssure with the lateral ventricles only slightly enlarged so that the intracranial pressure was not suspected to be increased at that time. Subsequent ultrasound scans showed a constant expansion of the lateral ventricles and the third ventricle without signs of an increased intracranial pressure so that an atrophic process was suspected. While the head circumference was close to the 97th percentile from birth to the age of 11 weeks, it increased rapidly thereafter to a maximum of 48 cm. At that a time a CT scan revealed a markedly asymmetrically enlarged cisterna magna with a reduced left cerebellar hemisphere not resembling a Dandy±Walker malformation as the vermis could be seen and was not malrotated. This is a condition which has hitherto not been reported to be associated with congenital myotonic dystrophy and should be considered in such patients when hydrocephalus develops. References [1] Harper PS. Myotonic dystrophy, Second ed.. London, Toronto, New York: J.B. Saunders, 1989. [2] de Die-Smulders CE, Smeets HJ, Loots W, Anten HB, Mirandolle JF, Geraedts JP, et al. Paternal transmission of congenital myotonic dystrophy. J Med Genet 1997;34:930±933. [3] Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, et al. Molecular basis of myotonic dystrophy; expansion of a trinucleotide (CTG) repeat at the 3 0 end of a transcript encoding a protein kinase family member. Cell 1992;68:799±808.
[4] Tsil®dis C, Mackenzie AE, Mettler G, Barcelo J, Korneluk R. Correlation between CTG trinucleotide repeat length and frequency of severe congenital myotonic dystrophy. Nat Genet 1992;1:192±195. [5] Hageman ATM, GabreeÈls FJM, Liem KD, Renkawek K, Boon JM. Congenital myotonic dystrophy; a report on 13 cases and a review of the literature. J Neurol Sci 1993;115:95±101. [6] Fuji T, Yorifuji T, Okuno T, Toyokuni S, Okada S, Mikawa H. Congenital myotonic dystrophy with progressive edema and hypoproteinemia. Brain Develop 1991;13:58±60. [7] A®® AM, Bhatia AR, Eyal F. Hydrops fetalis associated with congenital myotonic dystrophy. Am J Obstet Gynecol 1992;166:929±930. [8] Rais-Bahrami K, MacDonald MG, Eng GD, Rosenbaum KN. Persistent pulmonary hypertension in newborn infants with congenital myotonic dystrophy. J Pediatr 1994;124:634±635. [9] Reardon W, Newcombe R, Fenton I, Sibert J, Harper PS. The natural history of congenital myotonic dystrophy: mortality and long term clinical aspects. Arch Dis Child 1993;68:177±181. [10] Harper PS. Congenital myotonic dystrophy in Britain I. Clinical aspects. Arch Dis Child 1975;50:505±513. [11] MuÈller-Felber W, Schmidt-Achert M, Pongratz DE. Skeletal muscle in children with congenital myotonic dystrophy in the ®rst year of life. Clin Neuropathol 1993;12:211±214. [12] Zellweger H, Ionasescu V. Early onset of myotonic dystrophy in infants. Am J Dis Child 1973;125:601±604. [13] Hashimoto T, Tayama M, Miyazaki M, Murakawa K, Kawai H, Nishitani H, et al. Neuroimaging study of myotonic dystrophy I. Magnetic resonance imaging of the brain. Brain Develop 1995;17:24±27. [14] Garcia-Alix A, Cabanas F, Morales C, Pellicer A, Echevarria J, Paisan L, et al. Cerebral abnormalities in congenital myotonic dystrophy. Pediatr Neurol 1991;7:28±32. [15] Tanabe Y, Iai M, Tamai K, Fujimoto N, Sugita K. Neuroradiological ®ndings in children with congenital myotonic dystrophy. Acta Paediatr 1992;81:613±617. [16] Regev R, de Vries LS, Heckmatt JZ, Dubovitz V. Cerebral ventricular dilatation in congenital myotonic dystrophy. J Pediatr 1987;111:372± 376.
www.elsevier.com/locate/braindev
Case report
Occlusive hydrocephalus in congenital myotonic dystrophy Werner Rettwitz-Volk a,1,*, Mats Wikstroem b, Olof Flodmark c a
Pediatric Clinic, Krankenhaus Friedrichshafen, Germany Department of Radiology, Krankenhaus Friedrichshafen, Germany c Department of Neuroradiology, Karolinska Institute, Stockholm, Sweden b
Received 3 July 2000; received in revised form 11 December 2000; accepted 15 December 2000
Abstract A case of congenital myotonic dystrophy is reported which was complicated by the development of a hydrocephalus that needed ventricular-peritoneal shunting at the age of 4 months. Although dilatation of cerebral ventricles is a common feature in these patients, an occlusive hydrocephalus has not so far been reported. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Congenital myotonic dystrophy; Hydrocephalus
1. Introduction Congenital myotonic dystrophy represents the neonatal variant of Curschmann±Steinert myotonia and is an autosomal dominantly inherited condition with an incidence estimated to be 13/100 000 liveborns [1]. In general, the disease is transmitted by the mother although paternal transmission has been reported [2]. The molecular basis is an unstable DNA fragment consisting of a variable expansion of a CTG triplet at the 3 0 end of the gene encoding myotonin protein kinase which is localised on chromosome 19 (19q 13.2± 13.3) [3]. The severity of the disease is directly correlated to the length of the CTG sequence [4]. Affected newborns can present with intrauterine growth retardation, prematurity, birth asphyxia, respiratory distress often requiring mechanical ventilation [5] and always exhibit generalised muscular hypotonia [5]. Feeding problems are common [5] and an association with protein losing enteropathy [6], hydrops fetalis [7], and persistent pulmonary hypertension of the newborn [8] has been described. The initial muscular hypotonia usually improves so that the patients are able to walk with delay, but hypotonia tends to recur and myotonia ensues [1]. Twenty-®ve percent of the affected infants die within the ®rst 18 months of life, mainly during the neonatal period; half of the patients with Curschmann±Steinert myotonia reach their mid-30 s [9]. Most of * Corresponding author. Klinik fuÈr Kinder und Jugendliche, StaÈdtisches Krankenhaus Friedrichshafen Postfach 2360, D-88013 Friedrichshafen, Germany. Tel.: 149-75-4196-1450; fax: 149-75-4196-1266. 1 W. Rettwitz-Volk, BuÈrgerhospital Frankfurt, Nibelungenalle 37-41, D60318, Frankfurt, Germany.
them are severely mentally retarded with an IQ of 70 or less [10]. Muscle biopsy reveals only non-speci®c changes such as a selective atrophy of type 1 or type 2 muscle ®bers or no changes at all [11,12]. EMG and muscle enzymes are uninformative [12]. Imaging studies in patients with Curschmann±Steinert myotonia show ventriculomegaly [13,14,15], white matter lesions [13], hypoplastic corpus callosum [13], lesions of the cerebellum [13], macrocephaly [14], and periventricular hyperdensities [14]. Histological examination in some cases revealed neuronal migrational disturbance [14]. Although ventricular enlargement is a common feature in Curschmann±Steinert myotonia, increased intraventricular pressure requiring ventricular shunting has hitherto not been described. 2. Case report Our patient was the ®rst child of a 30-year-old primigravida/para. Pregnancy was uneventful and the infant was delivered at term by emergency caesarean section because of fetal bradycardia. One minute APGAR score was 3, arterial cord blood pH was 7.09, birth weight was 3250 g, and head circumference 37 cm (1 cm above 97th centile). As the girl showed no spontaneous breathing she was intubated and mechanical ventilation initiated. There was no need for supplemental oxygen and the main clinical feature was a marked muscular hypotonia and a tented upper lip was noted. On the 4th day of life the infant could be extubated although breathing dif®culties due to the muscular weakness persisted. As the clinical presentation suggested a congenital
0387-7604/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S03 87-7604(01)0017 6-0
W. Rettwitz-Volk et al. / Brain & Development 23 (2001) 122±124
myotonic dystrophy, strengthened by the typical symptoms of myotonia in the mother who was unaware of her condition until this very moment, further investigations were initiated. Molecular genetic studies revealed an expansion of a CTG triplet to 7 kb in the infant and to 0.8 kb in the mother. The defect was located in the myotonic dystrophy kinase gene in one allele with a normal second allele. Initial cranial ultrasound showed a mild enlargement of the lateral ventricles with a widening of the interhemispheric ®ssure (Fig. 1) and on the 15th day of life a marked cerebral ventriculomegaly as the only pathological ®nding could be seen. Intracranial perfusion remained undisturbed as could be shown by Doppler ultrasound. These ®ndings remained unchanged until discharge on day 35 when generalized muscular hypotonia was the main clinical feature. Subsequent monitoring showed a slowly progressive internal hydrocephalus without signs of increased intracranial pressure. From the age of about 11 weeks a rapidly increasing macrocephaly was noted and at the age of 14 weeks the girl presented with vomiting, lethargy and a tense anterior fontanelle. Head circumference was 48 cm (5.5 cm above 97th centile) at that time. CT scan showed a decompensating hydrocephalus (Fig. 2) and a permanent ventricular shunting was carried out. Additionally an asymmetrically enlarged cisterna magna could be seen (Fig. 3). After an uneventful further course the patient was discharged 4 weeks later. Subsequent cranial ultrasound scans revealed a mild ventricular enlargement with a normal perfusion as shown by Doppler ultrasound. At the last presentation at the age of 16 months, a marked muscular hypotonia was still apparent with psychomotor delay and a well functioning ventricularperitoneal shunt. 3. Discussion Ventricular enlargement is the most common neuropathological ®nding in Curschmann±Steinert myotonia. GarciaAlix et al. [14] found ventricular dilatation in 11 of 14
Fig. 1. Cranial ultrasound on the 2nd day of life. Mild ventricular enlargement and widening of the interhemispheric ®ssure.
123
Fig. 2. CT scan on week 14. Decompensating internal hydrocephalus.
affected infants as diagnosed by cranial ultrasound. Four infants showed a widening of the interhemispheric ®ssure as well and macrocephaly was noted in ten infants. There was no clinical sign of increased intracranial pressure. Tanabe et al. [15] saw ventricular dilatation in three of seven patients with Curschmann±Steinert myotonia and the condition did not progress in follow-up evaluation from 1 to 6 years. Hageman and co-workers [5] described nine cases of ventriculomegaly in their 13 patients and Hashimoto et al. [13] found not only enlargement of the lateral ventricles in all of their reported patients with Curschmann±Steinert myotonia but also enlargement of the third and fourth ventricles. The reason for this condition is not quite clear. In some cases an intraventricular hemorrhage preceded the hydrocephalus [16] while in others a cerebral dysgenesis was suspected [1] and a neuronal migrational disturbance was seen [14]. Neither in autopsied cases nor from clinical observations has a case of hydrocephalus with increased intracranial pressure been so far reported.
Fig. 3. CT scan on week 14. Asymmetrical enlargement of the cisterna magna with a reduced left cerebellar hemisphere.
124
W. Rettwitz-Volk et al. / Brain & Development 23 (2001) 122±124
The reason for the development of a hydrocephalus in our patient remains unclear. The sonographic examination on the 1st day of life showed a widening of the interhemispheric ®ssure with the lateral ventricles only slightly enlarged so that the intracranial pressure was not suspected to be increased at that time. Subsequent ultrasound scans showed a constant expansion of the lateral ventricles and the third ventricle without signs of an increased intracranial pressure so that an atrophic process was suspected. While the head circumference was close to the 97th percentile from birth to the age of 11 weeks, it increased rapidly thereafter to a maximum of 48 cm. At that a time a CT scan revealed a markedly asymmetrically enlarged cisterna magna with a reduced left cerebellar hemisphere not resembling a Dandy±Walker malformation as the vermis could be seen and was not malrotated. This is a condition which has hitherto not been reported to be associated with congenital myotonic dystrophy and should be considered in such patients when hydrocephalus develops. References [1] Harper PS. Myotonic dystrophy, Second ed.. London, Toronto, New York: J.B. Saunders, 1989. [2] de Die-Smulders CE, Smeets HJ, Loots W, Anten HB, Mirandolle JF, Geraedts JP, et al. Paternal transmission of congenital myotonic dystrophy. J Med Genet 1997;34:930±933. [3] Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, et al. Molecular basis of myotonic dystrophy; expansion of a trinucleotide (CTG) repeat at the 3 0 end of a transcript encoding a protein kinase family member. Cell 1992;68:799±808.
[4] Tsil®dis C, Mackenzie AE, Mettler G, Barcelo J, Korneluk R. Correlation between CTG trinucleotide repeat length and frequency of severe congenital myotonic dystrophy. Nat Genet 1992;1:192±195. [5] Hageman ATM, GabreeÈls FJM, Liem KD, Renkawek K, Boon JM. Congenital myotonic dystrophy; a report on 13 cases and a review of the literature. J Neurol Sci 1993;115:95±101. [6] Fuji T, Yorifuji T, Okuno T, Toyokuni S, Okada S, Mikawa H. Congenital myotonic dystrophy with progressive edema and hypoproteinemia. Brain Develop 1991;13:58±60. [7] A®® AM, Bhatia AR, Eyal F. Hydrops fetalis associated with congenital myotonic dystrophy. Am J Obstet Gynecol 1992;166:929±930. [8] Rais-Bahrami K, MacDonald MG, Eng GD, Rosenbaum KN. Persistent pulmonary hypertension in newborn infants with congenital myotonic dystrophy. J Pediatr 1994;124:634±635. [9] Reardon W, Newcombe R, Fenton I, Sibert J, Harper PS. The natural history of congenital myotonic dystrophy: mortality and long term clinical aspects. Arch Dis Child 1993;68:177±181. [10] Harper PS. Congenital myotonic dystrophy in Britain I. Clinical aspects. Arch Dis Child 1975;50:505±513. [11] MuÈller-Felber W, Schmidt-Achert M, Pongratz DE. Skeletal muscle in children with congenital myotonic dystrophy in the ®rst year of life. Clin Neuropathol 1993;12:211±214. [12] Zellweger H, Ionasescu V. Early onset of myotonic dystrophy in infants. Am J Dis Child 1973;125:601±604. [13] Hashimoto T, Tayama M, Miyazaki M, Murakawa K, Kawai H, Nishitani H, et al. Neuroimaging study of myotonic dystrophy I. Magnetic resonance imaging of the brain. Brain Develop 1995;17:24±27. [14] Garcia-Alix A, Cabanas F, Morales C, Pellicer A, Echevarria J, Paisan L, et al. Cerebral abnormalities in congenital myotonic dystrophy. Pediatr Neurol 1991;7:28±32. [15] Tanabe Y, Iai M, Tamai K, Fujimoto N, Sugita K. Neuroradiological ®ndings in children with congenital myotonic dystrophy. Acta Paediatr 1992;81:613±617. [16] Regev R, de Vries LS, Heckmatt JZ, Dubovitz V. Cerebral ventricular dilatation in congenital myotonic dystrophy. J Pediatr 1987;111:372± 376.