- Email: [email protected]
Schwartz Jampel syndrome in children
Case Reports / Journal of Clinical Neuroscience 20 (2013) 313–317 5. Mohyeddin Bonab M, Yazdanbakhsh S, Lotfi J, et al. Does mesenchymal stem cell therapy help multiple sclerosis patients? Report of a pilot study. Iran J Immunol 2007;4:50–7. 6. Karussis D, Karageorgiou C, Vaknin-Dembinsky A, et al. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol 2010;67:1187–94. 7. Yamout B, Hourani R, Salti H, et al. Bone marrow mesenchymal stem cell transplantation in patients with multiple sclerosis: a pilot study. J Neuroimmunol 2010;227:185–9.
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8. Connick P, Kolappan M, Crawley C, et al. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol 2012;11:150–6. 9. Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 2003;102:3837–44. 10. Wong RS. Mesenchymal stem cells: angels or demons? Journal of Biomedicine and Biotechnology 2011;2011:459510.
doi:http://dx.doi.org/10.1016/j.jocn.2012.01.057
Schwartz Jampel syndrome in children Ravindra Arya a, Suvasini Sharma a, Neerja Gupta b, Sushil Kumar a, Madhulika Kabra b, Sheffali Gulati a,⇑ a b
Division of Pediatric Neurology, Department of Pediatrics, 3rd floor, Teaching Block, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India Genetics Unit, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
a r t i c l e
i n f o
Article history: Received 7 January 2011 Accepted 12 January 2012
Keywords: Myotonic chondrodystrophy Schwartz Jampel syndrome SJS
a b s t r a c t Schwartz Jampel syndrome is a rare neuromuscular disorder with autosomal recessive inheritance characterized by myotonia, distinctive facial features including blepharospasm and a puckered chin, short stature and skeletal dysplasia. We report six Indian children with this disorder presenting with different clinical manifestations. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction In 1962 Oscar Schwartz and Robert Jampel described two siblings with blepharophimosis, puckered facial appearance, myopathy and joint deformities.1 Since then, the term Schwartz Jampel syndrome (SJS; also known as myotonic chondrodystrophy) has been applied to two genetically different conditions termed SJS type 1 and SJS type 2. This report is confined to the phenotype known as type 1A (Table 1). This variant was first documented by Catel in 1951.2 There is no prevalence data but it is acknowledged as a rare entity with about 50 cases documented in a 1992 review.2,3 Data from India have been limited to single-case reports.4–6 We describe six cases of SJS type 1A interesting for their rarity and varied clinical presentation.
2. Case reports 2.1. Patient 1 This 6-year-old girl presented with progressively increasing difficulty in opening her eyes and mouth since infancy. There was no history of seizures, altered consciousness, any cranial nerve involvement, limb weakness or any abnormal movements or diurnal variation. The child had age-appropriate development in all domains. On examination, she had short stature and distinctive facial features including a small forehead, supra-orbital ridging, bilateral blepharospasm, a small fish-like mouth and a puckered chin (Fig. 1a). Neurological examination showed hypertrophy of the deltoid and biceps muscles and generalized hyporeflexia, but no myotonia. Muscle strength and range of motion was normal in all ⇑ Corresponding author. Tel.: +91 986 839 7532. E-mail address: [email protected] (S. Gulati).
limbs. There were no contractures. A clinical diagnosis of SJS type 1A was made. Neurophysiologic evaluation revealed normal nerve conduction studies (NCS) with myotonia-like discharges without waxing and waning on needle electromyography (NEMG). The child was started on carbamazepine. Follow-up at 3 months showed increased palpebral fissure width and subjectively better eye and mouth opening. Botulinum toxin A (Botox; Allergan, Irvine, CA, USA) therapy for blepharospasm has been planned. 2.2. Patient 2 This 7.5-year-old girl presented with progressive scoliosis with convexity towards the right side in the mid-thoracic region, noticed since 3 years of age. Examination revealed the characteristic facial features of SJS of supra-orbital ridging, bilateral blepharospasm, a small mouth and a puckered chin (Fig. 1b). Neurological examination showed scoliosis and slight tightening of tendo-achilles bilaterally. A radiograph of the spine showed a Cobb angle of 35 degrees at the D5-D6 intervertebral disc, with platyspondyly and anisospondyly. Neurophysiologic evaluation showed normal NCS with myotonia-like discharges on NEMG. The child was managed with physical therapy and bracing and remains in follow-up. 2.3. Patient 3 This 6-year-old boy was referred with a diagnosis of developmental delay and facial dysmorphism. On evaluation he had normal, age-appropriate skills in all domains. Besides the characteristic facial features of SJS (Fig. 1c), he had short stature; bilateral hypertrophy of pectoralis major, deltoid, biceps, triceps and quadriceps femoris; and contractures at the elbows and heels. The child was initially treated with physical therapy and phenytoin but has since been lost to follow-up.
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Table 1 Clinical and genetic characteristics of Schwartz Jampel syndrome Type 1A
Type 1B
Type 2
Clinical profile
Usually manifests within first 3 years of life Common clinical features include stiffness, non-progressive muscle weakness, motor developmental problems, bone disease and characteristic facial gestalt
Similar to type 1A, but has increased severity of clinical manifestations Apparent immediately at birth, but not incompatible with even long-term survival
Genetic defect
HSPG2 gene, which codes for perlecan, a heparin sulfate proteoglycan
Same as type 1A; no genotype-phenotype correlation available
Separate disease known as Stuve-Wiedemann syndrome Apparent immediately at birth; clinical manifestations similar to those with type 1B.Cardinal features include joint contractures, bone dysplasia, small stature, severe respiratory difficulties, feeding problems, prominent hypotonia (rather than stiffness) and frequent bouts of hyperthermia. High infant mortality rate, with very rare long-term survival LIFR gene, which codes for leukemia inhibitory factor receptor
2.4. Patient 4 and patient 5 This 10-year-old boy and his 6.5-year-old sister were born to non-consanguineous parents. The boy was initially referred for evaluation of facial dysmorphism (Fig. 1d). The face had a pursed-lips appearance. There was no supra-orbital ridging or blepharospasm. His height was appropriate. An initial diagnosis of whistling face syndrome was considered. On follow-up, he developed progressive blepharophimosis and puckering of the chin. Needle electromyography showed characteristic myotonia-like discharges. At presentation, his sister had been developing chin puckering and blepharophimosis for 18 months (Fig. 1e). She had short stature, although radiographs of the spine and long bones showed no abnormality. Both children
were started on carbamazepine and physical therapy and remain in follow-up. 2.5. Patient 6 This 11-year-old boy was brought for evaluation of length discrepancy in his lower limbs. His right lower limb was found to be 5 cm shorter than the left one. Measurement revealed that this discrepancy was entirely due to a difference in thigh length, that is, the distance between the anterior superior iliac spine and the tibial tuberosity, with equal leg length. Facial features suggestive of SJS, including pursed lips and a puckered chin, were observed, although there was no blepharospasm (Fig. 1f). Radiographs of long bones revealed metaphyseal dysplasia (Fig. 2). Needle
Fig. 1. Clinical photographs of patients 1 to 6 ([a] to [f]) showing the characteristic triad of facial features: blepharospasm, pursed mouth and puckered chin. Note the impressive muscle hypertrophy in patient 5 (e) and absence of blepharospasm in patient six (f). (Photographs have been reproduced with the kind permission of the patients’ families and/or guardians). (This figure is available in colour at www.sciencedirect.com.)
Case Reports / Journal of Clinical Neuroscience 20 (2013) 313–317
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Fig. 2. Anterior–posterior (a) and lateral (b, c) radiographs showing metaphyseal dysplasia of the right knee of patient 6.
electromyography revealed complex repetitive discharges (CRD; Fig. 3) besides myotonia-like discharges. He is being managed with phenytoin and a shoe insert.
3. Discussion We report these cases to emphasize that this disorder can present with different manifestations, is recognizable on the basis of distinctive facial features and is treatable to some extent. Needle electromyography can demonstrate some characteristic features and substantiate the diagnosis when genetic testing is not available. The manifestations of SJS result from continuous muscle activity and skeletal dysplasia. Typically, SJS type 1A presents by 3 years to 4 years of age with myotonia, short stature, non-progressive muscle weakness, muscle hypertrophy, progressive restriction of range of motion and paucity of subcutaneous tissue. Facial features consist of blepharospasm as well as blepharophimosis, an immobile mask-like face, pursed lips and a puckered chin. Micrognathia, low-set ears with folded helices and dystopia canthorum have also been documented.2 Hypertrichosis of the eyelids was described in the original report.1 Skeletal features include a short neck, pectus carinatum, kyphoscoliosis, pes planus and developmental hip dysplasia. Other clinical features include carpal tunnel syndrome and propensity for malignant hyperpyrexia. Cognitive phenotype may include mental retardation (MR), developmental language disorder and attention deficit with hyperactivity in up to 20% of patients.2 Muscle weakness and contracture formation may result in a crouched stance with waddling gait. Rarely, myopia, inguinal and umbilical hernias and micro-orchidism have been documented.2 Our patients exhibited several of the classic features including facial gestalt, short stature and muscular hypertrophy. In addition, one of our patients (patient 6) presented only with limb length discrepancy. None of our patients had cognitive or behavioral problems. A child suspected of SJS should initially undergo neurophysiologic evaluation consisting of NCS and NEMG. Characteristic findings include spontaneous myotonia-like discharges which differ
from classic myotonia in having higher frequency and an absence of waxing and waning of amplitude and frequency. Failure to achieve electrical silence with rest, curarization or benzodiazepine administration implies that the generator is localized to muscle itself. In some cases, CRD have been documented and some authors consider all myotonia-like discharges seen in SJS to be CRD.3,7 In our patients we found characteristic myotonia-like discharges in all and CRD in one (Fig. 3). Skeletal survey in these patients might show vertebral anomalies including platyspondyly, anisospondyly, coronal clefts and failure of the anterior half of the vertebral body.2 One of our patients (patient 2) showed these anomalies as a cause for her scoliosis. Two of our patients with short stature (patients 1 and 5), however, had normal spine X-rays. Additional skeletal manifestations that have been described in patients with SJS include acetabular flattening, hip dysplasia, anterior bowing of long bone diaphysis, metaphyseal widening, misshapen capital femoral epiphysis and irregular cupping of the epiphysis around the knee joint.2 A metaphyseal dysplasia of the lower end of the femur as seen in our patient 6, has probably not been documented earlier. Patients with SJS 1A present dysmorphology similar to those with Freeman Sheldon and Marden Walker syndromes.2 Characteristics of Freeman Sheldon syndrome are a whistling face with puckered lips and microstomia, long philtrum and a dimpled chin. There is a peculiar ulnar deviation of the long fingers called windmill vane appearance. Characteristics of Marden Walker syndrome are immobile face with blepharophimosis and ptosis, multiple joint contractures and a higher incidence of MR. From a neurophysiologic perspective, SJS is usually grouped with non-dystrophy myotonic disorders. Patient 4 was initially thought to have whistling face syndrome but later he developed other characteristics of SJS. Schwartz Jampel syndrome has autosomal recessive inheritance. It results from defects in the perlecan protein (heparan sulfate proteoglycan 2) coded by the HSPG2 gene located on chromosome 1p34-35.8 Perlecan is a component of basement membranes9 and a defect in this protein or partial deficiency is thought to result in abnormal cartilage development and anomalous neuromuscular activity. Stum et al. have described a genetic study of 35 patients from 23 families. Most of the mutations were
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Case Reports / Journal of Clinical Neuroscience 20 (2013) 313–317
Fig. 3. Long trace (A) and raster trace (B) of needle electromyograph of spontaneous activity of the left biceps of patient 6 showing complex repetitive discharges (sensitivity 50 lV/division, time base 100 ms). (This figure is available in colour at www.sciencedirect.com.)
private and allowed for some functional protein production.9 The exact pathogenesis of SJS is not known; however, it is believed that perlecan is important for the localization of acetylcholinesterase (AChE) at the neuromuscular junction, and that continuous muscle fiber activity results from defects in this process. However, Stum et al. found that partial endplate AChE deficiency was not associated with spontaneous activity at rest in diaphragmatic NEMG.10 Perlecan abnormality leading to secondary ion channel dysfunction also remains a probability.3 Management of these children is best offered by a team comprising a neurologist, a geneticist, a physical therapist, an orthopedic surgeon, an ophthalmologist and a psychologist. Myotonia is partially responsive to sodium channel blockade with carbamazepine, phenytoin or procainamide. Early initiation of treatment probably limits the extent of disability. Physical therapy is important to prevent contracture formation and fixed skeletal deformity. Progressively worsening blepharospasm is an important morbidity in
children with SJS leading to blepharophimosis and interference with vision. Botox injection into the orbicularis oculi is usually helpful.11 In view of Botox-related ptosis, selective injection of the lower eyelid has also been tried.12 Rarely, surgical intervention is considered including orbicularis oculi myectomy or levator aponeurosis resection.11,13 Psychological support is required for stigmatization resulting from a different physical appearance. Schwartz Jampel syndrome type 1A is not thought to shorten lifespan.
References 1. Schwartz O, Jampel R. Congenital blepharophimosis associated with a unique generalized myopathy. Arch Ophthalmol 1962;68:52–7. 2. Viljoen D, Beighton P. Schwartz-Jampel syndrome (chondrodystrophic myotonia). J Med Genet 1992;29:58–62. 3. Ault J, Berman SA. Schwartz-Jampel Syndrome. 2010 [cited 2010 12/08/2010]; Available from: http://emedicine.medscape.com/article/1172013. 4. Kulkarni ML, Pillai R. Schwartz-Jampel syndrome. Indian Pediatr 2004;41:285.
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Case Reports / Journal of Clinical Neuroscience 20 (2013) 317–319 5. Naharajakumar, Subbulakshmi C, John E, et al. Crying or smiling? The SchwartzJampel syndrome. J Pediatr 2006;148:702. 6. Dhanrajani PJ, Abdulwassie HM. Schwartz-Jampel syndrome. A case report. Indian J Dent Res 1996;7:107–9. 7. Preston DC, Shapiro BE. Electromyography and neuromuscular disorders: clinical electrophysiologic correlations. 2nd ed. Philadelphia: Elsevier; 2005. 8. Nicole S, Ben Hamida C, Beighton P, et al. Localization of the Schwartz-Jampel syndrome (SJS) locus to chromosome 1p34–p36.1 by homozygosity mapping. Hum Mol Genet 1995;4:1633–6. 9. Stum M, Davoine CS, Vicart S, et al. Spectrum of HSPG2 (Perlecan) mutations in patients with Schwartz-Jampel syndrome. Hum Mutat 2006;27:1082–91. 10. Stum M, Girard E, Bangratz M, et al. Evidence of a dosage effect and a physiological endplate acetylcholinesterase deficiency in the first mouse
models mimicking Schwartz-Jampel syndrome neuromyotonia. Hum Mol Genet 2008;17:3166–79. 11. Vargel I, Canter HI, Topaloglu H, et al. Results of botulinum toxin: an application to blepharospasm Schwartz-Jampel syndrome. J Craniofac Surg 2006;17:656–60. 12. Flynn TC, Carruthers JA, Carruthers RA. Botulinum-A toxin treatment of the lower eyelid improves infraorbital rhytides and widens the eye. Dermatol Surg 2001;27:703–8. 13. Morrison DA, Mellington FB, Hamada S, et al. Schwartz-Jampel syndrome: surgical management of the myotonia-induced blepharospasm and acquired ptosis after failure with botulinum toxin A injections. Ophthal Plast Reconstr Surg 2006;22:57–9.
doi:http://dx.doi.org/10.1016/j.jocn.2012.01.057
Two patients with a solitary fibrous tumor of the thoracic spinal cord Marina Brigui a, Sorin Aldea a,⇑, Michele Bernier b, Saad Bennis a, Etienne Mireau a, Stephan Gaillard a a b
Department of Neurosurgery, Foch Hospital, 40 rue Worth, Suresnes 92150, France Department of Pathology, Foch Hospital, Suresnes, France
a r t i c l e
i n f o
Article history: Received 3 December 2011 Accepted 14 February 2012
Keywords: Solitary fibrous tumor Spine Spinal cord tumor Surgery
a b s t r a c t We report two patients with thoracic spinal solitary fibrous tumor (SFT). This report includes a patient with the first secondary SFT arising in the central nervous system from a pleural origin to our knowledge. The diagnosis was confirmed by histological and immunohistochemical analysis. Both patients underwent gross total resection of their tumors and did not show signs of local recurrence. The patient with the secondary lesion later presented with visceral dissemination. We review the reports of spinal SFT and discuss the diagnosis and therapeutic management of this intriguing entity.
1. Introduction Since the first description by Carneiro et al., in 1996,1 of a solitary fibrous tumor (SFT) in the spine, fewer than 30 patients have been reported. Due to its sometimes difficult diagnosis, the frequency of this generally benign neoplasm of enigmatic origin is probably underestimated. The current study reports two new patients with spinal intradural SFT, one of whom had a rare malignant form, and provides a review of its diagnosis and management.
Ó 2012 Elsevier Ltd. All rights reserved.
(GTR) was achieved. Histological examination showed fusiform nuclear cells dispersed in a loose matrix, with a low mitotic count. Immunohistochemistry demonstrated strong reactivity to CD34, as well as to Bcl12 and CD99 (Supplementary Fig. 1a–c). There was no immunoreactivity against epithelial membrane antigen (EMA) or PS100. The patient recovered well. At the last followup, 29 months after surgery, there was no evidence of clinical or radiological recurrence. 2.2. Patient 2
2. Case reports 2.1. Patient 1 A 56-year-old man, with no remarkable past medical history, presented with neuropathic pain of the right lower limb for 9 years. His symptoms worsened progressively in the left leg as pain and gait difficulties appeared. There was no motor weakness or bowel or bladder dysfunction. MRI revealed a 15-mm-long intradural lesion at T6–T7 (Fig. 1a, b). The tumor was isointense on both T1-weighted and T2-weighted MRI and was homogenously enhanced by gadolinium. A spinal angiogram did not demonstrate particular vascularity of the lesion. At surgery, after a T6–T8 laminectomy and opening of the dura mater, a firm, white intradural extramedullary lesion was found. The tumor presented an attachment to the pia mater and had a good cleavage plane with the spinal cord. Gross total resection ⇑ Corresponding author. Tel.: +33 146252007; fax: +33 146252069. E-mail address: [email protected] (S. Aldea).
A 69-year-old man underwent a wide resection of a 19-cm large mass of the left pleura, which had been diagnosed as an SFT (Fig. 2). This tumor had been under observation for nearly 20 years prior to surgery. Six months later, the patient presented with progressive back pain. Physical examination revealed signs of myelopathy. An MRI demonstrated an intraspinal, extradural right T7–T8 tumor with a transforaminal extension into the retropleural space. A preoperative spinal angiogram and embolization were performed (Fig. 3). GTR of the epidural mass was achieved through a T6–T8 laminectomy with T7–T8 arthrectomy and a posterior transpedicular fusion. Microscopic examination revealed a highly cellular spindle-cell tumor with necrosis and a mitotic index of 4 per 10 high power fields (HPF). Immunohistochemistry showed patchy and focal positivity for CD34 and strong positivity for Bcl2 (Supplementary Fig. 2a–c). The stains were negative for EMA. These findings were consistent with a malignant form of SFT. One year later, the patient underwent a second thoracotomy for recurrence of the left pleural tumor. A left inferior lobectomy was performed. Six months later, a CT-scan revealed a new locoregional relapse as well as metastases in the kidneys and subcutaneous tis-
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8. Connick P, Kolappan M, Crawley C, et al. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol 2012;11:150–6. 9. Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 2003;102:3837–44. 10. Wong RS. Mesenchymal stem cells: angels or demons? Journal of Biomedicine and Biotechnology 2011;2011:459510.
doi:http://dx.doi.org/10.1016/j.jocn.2012.01.057
Schwartz Jampel syndrome in children Ravindra Arya a, Suvasini Sharma a, Neerja Gupta b, Sushil Kumar a, Madhulika Kabra b, Sheffali Gulati a,⇑ a b
Division of Pediatric Neurology, Department of Pediatrics, 3rd floor, Teaching Block, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India Genetics Unit, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
a r t i c l e
i n f o
Article history: Received 7 January 2011 Accepted 12 January 2012
Keywords: Myotonic chondrodystrophy Schwartz Jampel syndrome SJS
a b s t r a c t Schwartz Jampel syndrome is a rare neuromuscular disorder with autosomal recessive inheritance characterized by myotonia, distinctive facial features including blepharospasm and a puckered chin, short stature and skeletal dysplasia. We report six Indian children with this disorder presenting with different clinical manifestations. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction In 1962 Oscar Schwartz and Robert Jampel described two siblings with blepharophimosis, puckered facial appearance, myopathy and joint deformities.1 Since then, the term Schwartz Jampel syndrome (SJS; also known as myotonic chondrodystrophy) has been applied to two genetically different conditions termed SJS type 1 and SJS type 2. This report is confined to the phenotype known as type 1A (Table 1). This variant was first documented by Catel in 1951.2 There is no prevalence data but it is acknowledged as a rare entity with about 50 cases documented in a 1992 review.2,3 Data from India have been limited to single-case reports.4–6 We describe six cases of SJS type 1A interesting for their rarity and varied clinical presentation.
2. Case reports 2.1. Patient 1 This 6-year-old girl presented with progressively increasing difficulty in opening her eyes and mouth since infancy. There was no history of seizures, altered consciousness, any cranial nerve involvement, limb weakness or any abnormal movements or diurnal variation. The child had age-appropriate development in all domains. On examination, she had short stature and distinctive facial features including a small forehead, supra-orbital ridging, bilateral blepharospasm, a small fish-like mouth and a puckered chin (Fig. 1a). Neurological examination showed hypertrophy of the deltoid and biceps muscles and generalized hyporeflexia, but no myotonia. Muscle strength and range of motion was normal in all ⇑ Corresponding author. Tel.: +91 986 839 7532. E-mail address: [email protected] (S. Gulati).
limbs. There were no contractures. A clinical diagnosis of SJS type 1A was made. Neurophysiologic evaluation revealed normal nerve conduction studies (NCS) with myotonia-like discharges without waxing and waning on needle electromyography (NEMG). The child was started on carbamazepine. Follow-up at 3 months showed increased palpebral fissure width and subjectively better eye and mouth opening. Botulinum toxin A (Botox; Allergan, Irvine, CA, USA) therapy for blepharospasm has been planned. 2.2. Patient 2 This 7.5-year-old girl presented with progressive scoliosis with convexity towards the right side in the mid-thoracic region, noticed since 3 years of age. Examination revealed the characteristic facial features of SJS of supra-orbital ridging, bilateral blepharospasm, a small mouth and a puckered chin (Fig. 1b). Neurological examination showed scoliosis and slight tightening of tendo-achilles bilaterally. A radiograph of the spine showed a Cobb angle of 35 degrees at the D5-D6 intervertebral disc, with platyspondyly and anisospondyly. Neurophysiologic evaluation showed normal NCS with myotonia-like discharges on NEMG. The child was managed with physical therapy and bracing and remains in follow-up. 2.3. Patient 3 This 6-year-old boy was referred with a diagnosis of developmental delay and facial dysmorphism. On evaluation he had normal, age-appropriate skills in all domains. Besides the characteristic facial features of SJS (Fig. 1c), he had short stature; bilateral hypertrophy of pectoralis major, deltoid, biceps, triceps and quadriceps femoris; and contractures at the elbows and heels. The child was initially treated with physical therapy and phenytoin but has since been lost to follow-up.
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Case Reports / Journal of Clinical Neuroscience 20 (2013) 313–317
Table 1 Clinical and genetic characteristics of Schwartz Jampel syndrome Type 1A
Type 1B
Type 2
Clinical profile
Usually manifests within first 3 years of life Common clinical features include stiffness, non-progressive muscle weakness, motor developmental problems, bone disease and characteristic facial gestalt
Similar to type 1A, but has increased severity of clinical manifestations Apparent immediately at birth, but not incompatible with even long-term survival
Genetic defect
HSPG2 gene, which codes for perlecan, a heparin sulfate proteoglycan
Same as type 1A; no genotype-phenotype correlation available
Separate disease known as Stuve-Wiedemann syndrome Apparent immediately at birth; clinical manifestations similar to those with type 1B.Cardinal features include joint contractures, bone dysplasia, small stature, severe respiratory difficulties, feeding problems, prominent hypotonia (rather than stiffness) and frequent bouts of hyperthermia. High infant mortality rate, with very rare long-term survival LIFR gene, which codes for leukemia inhibitory factor receptor
2.4. Patient 4 and patient 5 This 10-year-old boy and his 6.5-year-old sister were born to non-consanguineous parents. The boy was initially referred for evaluation of facial dysmorphism (Fig. 1d). The face had a pursed-lips appearance. There was no supra-orbital ridging or blepharospasm. His height was appropriate. An initial diagnosis of whistling face syndrome was considered. On follow-up, he developed progressive blepharophimosis and puckering of the chin. Needle electromyography showed characteristic myotonia-like discharges. At presentation, his sister had been developing chin puckering and blepharophimosis for 18 months (Fig. 1e). She had short stature, although radiographs of the spine and long bones showed no abnormality. Both children
were started on carbamazepine and physical therapy and remain in follow-up. 2.5. Patient 6 This 11-year-old boy was brought for evaluation of length discrepancy in his lower limbs. His right lower limb was found to be 5 cm shorter than the left one. Measurement revealed that this discrepancy was entirely due to a difference in thigh length, that is, the distance between the anterior superior iliac spine and the tibial tuberosity, with equal leg length. Facial features suggestive of SJS, including pursed lips and a puckered chin, were observed, although there was no blepharospasm (Fig. 1f). Radiographs of long bones revealed metaphyseal dysplasia (Fig. 2). Needle
Fig. 1. Clinical photographs of patients 1 to 6 ([a] to [f]) showing the characteristic triad of facial features: blepharospasm, pursed mouth and puckered chin. Note the impressive muscle hypertrophy in patient 5 (e) and absence of blepharospasm in patient six (f). (Photographs have been reproduced with the kind permission of the patients’ families and/or guardians). (This figure is available in colour at www.sciencedirect.com.)
Case Reports / Journal of Clinical Neuroscience 20 (2013) 313–317
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Fig. 2. Anterior–posterior (a) and lateral (b, c) radiographs showing metaphyseal dysplasia of the right knee of patient 6.
electromyography revealed complex repetitive discharges (CRD; Fig. 3) besides myotonia-like discharges. He is being managed with phenytoin and a shoe insert.
3. Discussion We report these cases to emphasize that this disorder can present with different manifestations, is recognizable on the basis of distinctive facial features and is treatable to some extent. Needle electromyography can demonstrate some characteristic features and substantiate the diagnosis when genetic testing is not available. The manifestations of SJS result from continuous muscle activity and skeletal dysplasia. Typically, SJS type 1A presents by 3 years to 4 years of age with myotonia, short stature, non-progressive muscle weakness, muscle hypertrophy, progressive restriction of range of motion and paucity of subcutaneous tissue. Facial features consist of blepharospasm as well as blepharophimosis, an immobile mask-like face, pursed lips and a puckered chin. Micrognathia, low-set ears with folded helices and dystopia canthorum have also been documented.2 Hypertrichosis of the eyelids was described in the original report.1 Skeletal features include a short neck, pectus carinatum, kyphoscoliosis, pes planus and developmental hip dysplasia. Other clinical features include carpal tunnel syndrome and propensity for malignant hyperpyrexia. Cognitive phenotype may include mental retardation (MR), developmental language disorder and attention deficit with hyperactivity in up to 20% of patients.2 Muscle weakness and contracture formation may result in a crouched stance with waddling gait. Rarely, myopia, inguinal and umbilical hernias and micro-orchidism have been documented.2 Our patients exhibited several of the classic features including facial gestalt, short stature and muscular hypertrophy. In addition, one of our patients (patient 6) presented only with limb length discrepancy. None of our patients had cognitive or behavioral problems. A child suspected of SJS should initially undergo neurophysiologic evaluation consisting of NCS and NEMG. Characteristic findings include spontaneous myotonia-like discharges which differ
from classic myotonia in having higher frequency and an absence of waxing and waning of amplitude and frequency. Failure to achieve electrical silence with rest, curarization or benzodiazepine administration implies that the generator is localized to muscle itself. In some cases, CRD have been documented and some authors consider all myotonia-like discharges seen in SJS to be CRD.3,7 In our patients we found characteristic myotonia-like discharges in all and CRD in one (Fig. 3). Skeletal survey in these patients might show vertebral anomalies including platyspondyly, anisospondyly, coronal clefts and failure of the anterior half of the vertebral body.2 One of our patients (patient 2) showed these anomalies as a cause for her scoliosis. Two of our patients with short stature (patients 1 and 5), however, had normal spine X-rays. Additional skeletal manifestations that have been described in patients with SJS include acetabular flattening, hip dysplasia, anterior bowing of long bone diaphysis, metaphyseal widening, misshapen capital femoral epiphysis and irregular cupping of the epiphysis around the knee joint.2 A metaphyseal dysplasia of the lower end of the femur as seen in our patient 6, has probably not been documented earlier. Patients with SJS 1A present dysmorphology similar to those with Freeman Sheldon and Marden Walker syndromes.2 Characteristics of Freeman Sheldon syndrome are a whistling face with puckered lips and microstomia, long philtrum and a dimpled chin. There is a peculiar ulnar deviation of the long fingers called windmill vane appearance. Characteristics of Marden Walker syndrome are immobile face with blepharophimosis and ptosis, multiple joint contractures and a higher incidence of MR. From a neurophysiologic perspective, SJS is usually grouped with non-dystrophy myotonic disorders. Patient 4 was initially thought to have whistling face syndrome but later he developed other characteristics of SJS. Schwartz Jampel syndrome has autosomal recessive inheritance. It results from defects in the perlecan protein (heparan sulfate proteoglycan 2) coded by the HSPG2 gene located on chromosome 1p34-35.8 Perlecan is a component of basement membranes9 and a defect in this protein or partial deficiency is thought to result in abnormal cartilage development and anomalous neuromuscular activity. Stum et al. have described a genetic study of 35 patients from 23 families. Most of the mutations were
316
Case Reports / Journal of Clinical Neuroscience 20 (2013) 313–317
Fig. 3. Long trace (A) and raster trace (B) of needle electromyograph of spontaneous activity of the left biceps of patient 6 showing complex repetitive discharges (sensitivity 50 lV/division, time base 100 ms). (This figure is available in colour at www.sciencedirect.com.)
private and allowed for some functional protein production.9 The exact pathogenesis of SJS is not known; however, it is believed that perlecan is important for the localization of acetylcholinesterase (AChE) at the neuromuscular junction, and that continuous muscle fiber activity results from defects in this process. However, Stum et al. found that partial endplate AChE deficiency was not associated with spontaneous activity at rest in diaphragmatic NEMG.10 Perlecan abnormality leading to secondary ion channel dysfunction also remains a probability.3 Management of these children is best offered by a team comprising a neurologist, a geneticist, a physical therapist, an orthopedic surgeon, an ophthalmologist and a psychologist. Myotonia is partially responsive to sodium channel blockade with carbamazepine, phenytoin or procainamide. Early initiation of treatment probably limits the extent of disability. Physical therapy is important to prevent contracture formation and fixed skeletal deformity. Progressively worsening blepharospasm is an important morbidity in
children with SJS leading to blepharophimosis and interference with vision. Botox injection into the orbicularis oculi is usually helpful.11 In view of Botox-related ptosis, selective injection of the lower eyelid has also been tried.12 Rarely, surgical intervention is considered including orbicularis oculi myectomy or levator aponeurosis resection.11,13 Psychological support is required for stigmatization resulting from a different physical appearance. Schwartz Jampel syndrome type 1A is not thought to shorten lifespan.
References 1. Schwartz O, Jampel R. Congenital blepharophimosis associated with a unique generalized myopathy. Arch Ophthalmol 1962;68:52–7. 2. Viljoen D, Beighton P. Schwartz-Jampel syndrome (chondrodystrophic myotonia). J Med Genet 1992;29:58–62. 3. Ault J, Berman SA. Schwartz-Jampel Syndrome. 2010 [cited 2010 12/08/2010]; Available from: http://emedicine.medscape.com/article/1172013. 4. Kulkarni ML, Pillai R. Schwartz-Jampel syndrome. Indian Pediatr 2004;41:285.
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Case Reports / Journal of Clinical Neuroscience 20 (2013) 317–319 5. Naharajakumar, Subbulakshmi C, John E, et al. Crying or smiling? The SchwartzJampel syndrome. J Pediatr 2006;148:702. 6. Dhanrajani PJ, Abdulwassie HM. Schwartz-Jampel syndrome. A case report. Indian J Dent Res 1996;7:107–9. 7. Preston DC, Shapiro BE. Electromyography and neuromuscular disorders: clinical electrophysiologic correlations. 2nd ed. Philadelphia: Elsevier; 2005. 8. Nicole S, Ben Hamida C, Beighton P, et al. Localization of the Schwartz-Jampel syndrome (SJS) locus to chromosome 1p34–p36.1 by homozygosity mapping. Hum Mol Genet 1995;4:1633–6. 9. Stum M, Davoine CS, Vicart S, et al. Spectrum of HSPG2 (Perlecan) mutations in patients with Schwartz-Jampel syndrome. Hum Mutat 2006;27:1082–91. 10. Stum M, Girard E, Bangratz M, et al. Evidence of a dosage effect and a physiological endplate acetylcholinesterase deficiency in the first mouse
models mimicking Schwartz-Jampel syndrome neuromyotonia. Hum Mol Genet 2008;17:3166–79. 11. Vargel I, Canter HI, Topaloglu H, et al. Results of botulinum toxin: an application to blepharospasm Schwartz-Jampel syndrome. J Craniofac Surg 2006;17:656–60. 12. Flynn TC, Carruthers JA, Carruthers RA. Botulinum-A toxin treatment of the lower eyelid improves infraorbital rhytides and widens the eye. Dermatol Surg 2001;27:703–8. 13. Morrison DA, Mellington FB, Hamada S, et al. Schwartz-Jampel syndrome: surgical management of the myotonia-induced blepharospasm and acquired ptosis after failure with botulinum toxin A injections. Ophthal Plast Reconstr Surg 2006;22:57–9.
doi:http://dx.doi.org/10.1016/j.jocn.2012.01.057
Two patients with a solitary fibrous tumor of the thoracic spinal cord Marina Brigui a, Sorin Aldea a,⇑, Michele Bernier b, Saad Bennis a, Etienne Mireau a, Stephan Gaillard a a b
Department of Neurosurgery, Foch Hospital, 40 rue Worth, Suresnes 92150, France Department of Pathology, Foch Hospital, Suresnes, France
a r t i c l e
i n f o
Article history: Received 3 December 2011 Accepted 14 February 2012
Keywords: Solitary fibrous tumor Spine Spinal cord tumor Surgery
a b s t r a c t We report two patients with thoracic spinal solitary fibrous tumor (SFT). This report includes a patient with the first secondary SFT arising in the central nervous system from a pleural origin to our knowledge. The diagnosis was confirmed by histological and immunohistochemical analysis. Both patients underwent gross total resection of their tumors and did not show signs of local recurrence. The patient with the secondary lesion later presented with visceral dissemination. We review the reports of spinal SFT and discuss the diagnosis and therapeutic management of this intriguing entity.
1. Introduction Since the first description by Carneiro et al., in 1996,1 of a solitary fibrous tumor (SFT) in the spine, fewer than 30 patients have been reported. Due to its sometimes difficult diagnosis, the frequency of this generally benign neoplasm of enigmatic origin is probably underestimated. The current study reports two new patients with spinal intradural SFT, one of whom had a rare malignant form, and provides a review of its diagnosis and management.
Ó 2012 Elsevier Ltd. All rights reserved.
(GTR) was achieved. Histological examination showed fusiform nuclear cells dispersed in a loose matrix, with a low mitotic count. Immunohistochemistry demonstrated strong reactivity to CD34, as well as to Bcl12 and CD99 (Supplementary Fig. 1a–c). There was no immunoreactivity against epithelial membrane antigen (EMA) or PS100. The patient recovered well. At the last followup, 29 months after surgery, there was no evidence of clinical or radiological recurrence. 2.2. Patient 2
2. Case reports 2.1. Patient 1 A 56-year-old man, with no remarkable past medical history, presented with neuropathic pain of the right lower limb for 9 years. His symptoms worsened progressively in the left leg as pain and gait difficulties appeared. There was no motor weakness or bowel or bladder dysfunction. MRI revealed a 15-mm-long intradural lesion at T6–T7 (Fig. 1a, b). The tumor was isointense on both T1-weighted and T2-weighted MRI and was homogenously enhanced by gadolinium. A spinal angiogram did not demonstrate particular vascularity of the lesion. At surgery, after a T6–T8 laminectomy and opening of the dura mater, a firm, white intradural extramedullary lesion was found. The tumor presented an attachment to the pia mater and had a good cleavage plane with the spinal cord. Gross total resection ⇑ Corresponding author. Tel.: +33 146252007; fax: +33 146252069. E-mail address: [email protected] (S. Aldea).
A 69-year-old man underwent a wide resection of a 19-cm large mass of the left pleura, which had been diagnosed as an SFT (Fig. 2). This tumor had been under observation for nearly 20 years prior to surgery. Six months later, the patient presented with progressive back pain. Physical examination revealed signs of myelopathy. An MRI demonstrated an intraspinal, extradural right T7–T8 tumor with a transforaminal extension into the retropleural space. A preoperative spinal angiogram and embolization were performed (Fig. 3). GTR of the epidural mass was achieved through a T6–T8 laminectomy with T7–T8 arthrectomy and a posterior transpedicular fusion. Microscopic examination revealed a highly cellular spindle-cell tumor with necrosis and a mitotic index of 4 per 10 high power fields (HPF). Immunohistochemistry showed patchy and focal positivity for CD34 and strong positivity for Bcl2 (Supplementary Fig. 2a–c). The stains were negative for EMA. These findings were consistent with a malignant form of SFT. One year later, the patient underwent a second thoracotomy for recurrence of the left pleural tumor. A left inferior lobectomy was performed. Six months later, a CT-scan revealed a new locoregional relapse as well as metastases in the kidneys and subcutaneous tis-