|Year : 2021 | Volume
| Issue : 3 | Page : 184-193
Congenital myopathies: A clinicopathological study of 10 cases in a tertiary care hospital of North India
Siddharth Maheshwari1, Ishita Pant2, Kiran Bala3, Vibhor Paradasani1
1 Department of Neurology, Institute of Human Behaviour & Allied Sciences, Delhi, India
2 Department Neuropathology, Institute of Human Behaviour & Allied Sciences, Delhi, India
3 Department of Neurology, Pandit Bhagwat Dayal Sharma Medical College, Rohtak, Haryana, India
|Date of Submission||18-Feb-2020|
|Date of Decision||07-Jul-2020|
|Date of Acceptance||08-Jul-2020|
|Date of Web Publication||11-Oct-2021|
Dr. Siddharth Maheshwari
Department of Neurology, Institute of Human Behavior and Allied Sciences, Dilshad Garden, New Delhi 110095
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Objective: Congenital myopathies (CMs) are rare neuromuscular disorders. Through this article, authors want to present a clinicopathological study of 10 cases of CM. Materials and Methods: The study included patients with histopathologically confirmed CM attending the neurology services at the Institute of Human Behavior and Allied Sciences for 2 years. After collecting the demographic data, all patients were subjected to comprehensive workup including a detailed neurological examination and investigations, including muscle biopsy from representative involved muscle. Results: Ten patients diagnosed with CM. The most common CM type was congenital fiber-type disproportion (CFTD) seen in four cases followed by centronuclear myopathy in two cases and one each in desmin-related myopathy, central core disease, nemaline myopathy, CM with type II fiber hypoplasia. Clinically, they have variable features. Conclusion: This study from India highlights the importance of specific clinical features to look for when suspecting a CM coupled with specific features in histopathology. However, studies with longer duration are needed to find out the true prevalence and various spectra of CMs.
Keywords: Clinicopathological, congenital myopathies, enzyme histochemistry, muscle biopsy
|How to cite this article:|
Maheshwari S, Pant I, Bala K, Paradasani V. Congenital myopathies: A clinicopathological study of 10 cases in a tertiary care hospital of North India. J Pediatr Neurosci 2021;16:184-93
| Introduction|| |
Congenital myopathies (CMs) collectively denote a term used to describe a heterogeneous group of inherited muscle diseases that are typically present at birth or in the first year of life with reduced fetal movements or delay of motor milestones, as well as weakness and hypotonia. The first description of CM, eventually known as central core disease (CCD), appeared in 1956. In 1969, Dubowitz classified these disorders terming them CMs. Clinically, the CMs have some common features, such as generalized weakness, hypotonia, hyporeflexia, poor muscle bulk, and dysmorphic features (e.g., chest deformities, foot deformities, high arch palate, and elongated facies). However, there is a wide variation in clinical severity within each subtype. The diagnosis of a specific CM should be made only in the presence of the characteristic pathologic features and not based on the clinical syndrome alone. This study was planned to investigate the clinical, electrophysiological, and histopathological profile of patients of CM from an Indian perspective. We report a series of 10 cases of CM and, to the best of our knowledge, this is the third-largest series from India. Earlier 100 and 25 cases had been reported by Gayatri et al. and Jain et al., respectively.
| Materials and Methods|| |
Study included patients with histopathologically confirmed CM attending the neurology services at the Institute of Human Behavior and Allied Sciences during 2 years. Written informed consent was taken from all the subjects/their parents/attendants. After collecting the demographic data, all patients were subjected to comprehensive workup including a detailed neurological examination and investigations. They underwent routine investigations including complete blood counts, blood sugar, serum urea, and creatinine, liver function test, and electrolytes. Motor and sensory nerve conductions and needle electromyography were performed muscle biopsy was done from representative involved muscle.
| Results|| |
This study was conducted in the Department of Neurology, Institute of Human Behavior and Allied Sciences, Dilshad Garden, Delhi for 2 years. It included 10 patients biopsy (histopathologically) proven cases. There were seven males and three females. The age at diagnosis ranged from newborn to 35-year-old with a mean age of 7.5 years. In all patients except Case 4, symptoms were started in the first decade of life with three of them presenting at the time of birth. The most common clinical features were delayed motor milestones (72.2%) followed by skeletal deformities (66.6%), high arched palate (50%), and difficulty in running and getting up (44.4%).
The most common CM type was congenital fiber-type disproportion (CFTD) seen in four cases followed by centronuclear myopathy (CNM) in two cases and one each in desmin-related myopathy (DRM), CCD, nemaline myopathy (NM), and CM with type II fiber hypoplasia.
The salient clinical features are as follows.
A 28-year-old male resident of Karnal, Haryana, presented with a history of difficulty in walking for 6 months. He had difficulty in climbing stairs, standing from sitting position, squatting, and history of frequent falls while running. He also had swallowing difficulty without any nasal regurgitation for the last 1 month. There was a history of preterm delivery in 8 months with delayed motor milestones. The patient had an elongated facies with the high arched palate and generalized hypotonia. He had wasting of bilateral quadriceps femoris with proximal weakness in both lower and upper limbs (LL > UL). The rest of the central nervous system examination was normal. His routine investigations were normal and creatine phosphokinase (CPK) was 48 IU/mL with a myopathic electromyography (EMG). The final histopathological diagnosis was CNM [Figure 1].
|Figure 1: Photomicrograph (Case 6) of muscle biopsy showing normal preserved architecture (A) H&E, ×400. (B) Disproportion in distribution of fibers size (inset) on enzyme histochemistry with NADH, ×400. Photomicrograph (Case 6) of muscle biopsy showing normal preserved architecture on enzyme histochemistry with disproportion in distribution of both type of fibers on ATPase 9.5, ×400 (C) |
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A 20-year-old male, resident of Balia, UP, with normal birth and developmental history presented with 12 years’ history of weakness in both lower limbs, in the form of repeated tripping, followed by difficulty in standing from squatting posture. He also had difficulty in raising the arms above the shoulder for the last 6 years. The patient had high arched palate and dorsal kyphosis. He had prominent wasting of bilateral infraspinati, teres major, and quadriceps with hypertrophied extensor digitorum brevis (EDB) and tendoachilles contracture. His higher mental functions and cranial nerves were normal. Motor system examination revealed generalized hypotonia. There was generalized areflexia and waddling gait. The presence of rimmed vacuole-like structures and eosinophilic inclusions was suggestive of a protein surplus myopathy most likely desminopathy [Figure 2].
|Figure 2: Photomicrograph (Case 3) on (A) H&E, ×200 normal fascicular architecture with mild increase in perimysial and endomysial connective tissue (arrow). Photomicrograph (Case 3) on (B) NADH, ×400 showing normal fascicular architecture with variation in fiber size (solid arrow) ranging from hypotrophic (blue arrow) normal (red arrow) to hypertrophic fibers (green arrow). (C) Immunopositivity seen with dystrophin (arrow) |
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A 13-year-old male, resident of UP, with the normal birth history presented with a history of delayed motor milestones and delayed speech (only Bisyllabe). He had recurrent falls during walking, difficulty in standing from sitting position, and taking overhead objects from the last 3–4 months. The patient had kyphoscoliosis, high arched palate with bilateral pescavus. There were bilateral scapular winging, ankle contracture, and calf hypertrophy. Systemic examination including higher mental function and cranial nerves were normal. Motor system examination revealed generalized hypotonia. Clinical possibilities of muscular dystrophy and CM were discussed. The histopathological diagnosis was suggestive of CFTD [Figure 3].
|Figure 3: Photomicrograph (Case 5) showing well-preserved architecture with no significant replacement by fibrofatty tissue or internalization of nuclei. Photomicrograph (A) there is predominance of type II fibers with peripheral accumulation of reaction product in some (solid arrow). Type I fibers are comparatively smaller in size and at places seen in groups (dotted arrow) (B) NADH, X200, (C) NADH, ×400 |
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A 31-year-old female, resident of Kanpur, UP, with normal birth history but with delayed motor milestones presented with a history of progressive dysphagia, drooping of both eyelids and nasal intonation of voice for 7 years with frequent respiratory tract infections (RTIs). Examination revealed bilateral ptosis, ophthalmoplegia, and high arched palate. There was wasting of bilateral temporalis muscle. Speech was hypovolumic with nasal intonation. Systemic examination revealed generalized hypotonia and proximal weakness in both the upper and lower limbs. Clinical diagnosis of mitochondrial cytopathy and CM were considered. Her routine blood investigations were normal and CK was 168 IU/mL. EMG revealed sharp, small duration polyphasic. The above biopsy findings were in favor of the CCD [Figure 4].
|Figure 4: Photomicrograph (Case 8) showing well preserved architecture with few fibers showing internalization (arrow) and clumping of nuclei (A) H&E, ×400. Photomicrograph (Case 8) showing moderate variation in fiber size varying from atrophic (red arrow) to hypertrophic fibers (black arrow) with mild increase in perimysial fibroconnective tissue (B) NADH, ×400, and (C) membranous immunopositivity with dystrophin, ×400|
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A 14-year-old female, a resident of Ghaziabad, UP with normal full-term vaginal delivery at a hospital with an antenatal history of decreased fetal movements presented with a history of delayed motor milestones including neck holding ~ 9 months, sitting with support ~ 1½ years and never walk independently, not able to comb, had difficulty in standing from sitting position. She had high arched palate, kyphoscoliosis with pes cavus. There was proximal muscle weakness in bilateral upper and lower limbs with MRC grade power of 3+/5 in upper limbs and 3–/5 in lower limbs with retained reflexes and normal plantar. Rest of the systemic examination was normal. Her CPK was 128 IU/mL. EMG revealed no spontaneous activity with myopathic MUAPs. Biopsy revealed CFTD [Supplementary Figure 1].
|Supplementary Figure 1: Photomicrograph (Case 1) of longitudinal section showing (A) centrally located short chains of nuclei (arrow). (B) Transverse section showing presence of centrally located nucleus in over 80% (arrow) of the fibers, most of the fibers contains only single nuclei, small clusters of nuclei are also seen in fair number of fibers. Photomicrograph (Case 1) of (C) SDH, and (D) NADH stains, the central area appears clear (solid arrow) with condensed reaction product at the periphery (dotted arrow) |
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A 9½-year-old female, resident of Eta, UP, presented with a history of delayed cry with delayed developmental milestones with inability to close her eyes and mouth completely since birth. Her weakness was confined to facial muscles and muscles of mastication. Examination revealed pes cavus with proximal weakness in both upper and lower limbs. Her CPK was 162 IU/mL. EMG revealed no spontaneous activity with myopathic MUAPs. The histopathological findings were suggestive of congenital fiber disproportion myopathy [Supplementary Figure 2].
|Supplementary Figure 2: Photomicrograph (Case 10) on H&E, ×200 (A) architecture is well preserved. Increase in perimysial connective tissue (arrow). Endomysium shows polygonal fibers with internalization of nuclei. (B) H&E, ×400 hypoplastic fibers (solid arrow) are seen randomly distributed among the normal or mildly hypertrophic fibers (dotted arrow). Photomicrograph (Case 10) on enzyme histochemistry with (C) NADH, X200, fiber differentiation is preserved. There is involvement of both fiber type and hypoplastic fibers are predominantly seen to be type I (arrow) |
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A 1½-year-old male, resident of Delhi, with normal birth history, presented with delayed motor milestones like not able to hold neck, not able to sit and stand without support. He had high arched palate, kyphoscoliosis with cubitus varus deformity. Systemic examination revealed generalized hypotonia with retained reflexes and no wasting with CPK 58 IU/mL. In EMG, there was no spontaneous activity recorded and rest of the examination was not possible because of poor cooperation. The histopathological features were suggestive of NM [Figure 5].
|Figure 5: Photomicrograph (Case 4) on (A) H&E, ×200 showing well preserved architecture with fibers in a mosaic pattern of arrangement. Variation in fiber diameter with small diameter fibers (solid arrow) scattered in between singly or in small groups. (B) Enzyme histochemistry with NADH, ×200 shows lack of differentiation at places, oxidative enzyme activity is seen to be devoid (dotted arrow) or, at places, concentrated in the central area in a large number of fibers|
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A 8-year-old male, resident of Delhi, with the normal birth history presented with delayed motor milestones like neck holding at 10 months, sitting without support at 2½ years, and not able to walk yet. He had dolicocephaly with kyphosis and high arched palate. He had wasting of bilateral temporalis muscle. Higher mental function including cranial nerves was normal. There was generalized wasting with hypotonia more in lower limbs than upper limbs. His power on MRC grade could not be assessed as the patient was having bilateral knee, ankle, and elbow contractures. The findings were suggestive of CFTD [Supplementary Figure 3].
|Supplementary Figure 3: Photomicrograph (Case 2) on (A) H&E, ×200 showing well preserved fascicular architecture, fiber size variation is moderate. (B) H&E, ×400 fiber showing irregular eosinophilic inclusions (dotted arrows) and in occasional ones structures looking like rimmed vacoules (solid arrows) seen. Photomicrograph (Case 2) type II fiber predominance (dotted arrow) seen on enzyme histochemistry with NADH and presence of desmin (solid arrows)|
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A 8½-year-old male, resident of M.P., with the normal birth history presented with a history of delayed motor milestones like neck holding at 2 years, sitting with support at 2½ years and walking with support at 3 years. He had short stature with dolicocephaly, high arched palate, and dorsal kyphosis. Cubitus varus (L > R) was also noted. His complaint was non-progressive with no members in family having similar complaints. Rest of the milestones was normal. Systemic examination revealed hypotonia with proximal weakness in both upper and lower limbs. The above findings were in favor of CM with type II fiber hypoplasia [Figure 6].
|Figure 6: Clinical photograph (Case 9) showing dolicocephaly (A) and a high arched palate (B). Photomicrograph (Case 9) showing well preserved architecture on (A) H&E, ×200. Photomicrograph (Case 9) on (b) NADH, ×200––Type II fibers appears to be smaller in size with mild grouping (solid arrow), there is relative hypertrophy of type I fibers (dotted arrow). On (C) NADH, ×400, small and grouped type II fibers seen |
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A 19-year-old female, resident of Delhi, with normal birth and developmental history presented with a history of weakness of both lower limbs since 10 years, weakness in left upper limb since 4 years, and difficulty in arising from bed since 3 years. She had hammer toe, pes cavus, and scoliosis. Scapular winging was present and she had prominent EDB bilaterally. She had bilateral foot drop with ankle contractures. Her CPK was 79 IU/mL. Pathological diagnosis was CNM [Figure 7].
|Figure 7: Photomicrograph (Case 7) architecture of the muscle is well preserved with mild increase in focal perimysial areas. Small, fairly rounded fibers with eccentric nuclei seen in groups (solid arrow) and the remaining larger fibers with a polygonal (dotted arrow) outline (A) H&E, ×400. Photomicrograph (Case 7) enzyme histochemistry with NADH (B) ×200, and (C) ×400 showing clusters of small fibers (arrows) characterized as type I|
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| Discussion|| |
CMs are a group of neuromuscular disorders characterized by early onset of muscular weakness with slow or nor progression. The presentation is nonspecific and clinically it is difficult to distinguish between various subtype This study was conducted in the Department of Neurology, IHBAS. During this period of around 2 years, patients diagnosed with CM. The most common CM type was CFTD seen in four cases followed by CNM in 2 cases and 1 each in DRM, CCD, NM, CM with type II fiber hypoplasia. Study from South India on 100 patients of CM over 20 years was reported by Gayathri et al. had shown the spectrum of CM as CNM (n = 39), myotubular myopathy (MTM) (n = 5), CFTD (n = 35), CCD (n = 9), multimini core disease (MCD) (n = 7), and one case with tubular aggregates. However, a 6 years study from North India by Jain et al. described the most common CM to be CCD (24%) followed by NM (20%), MCD (20%), CFTD (16%), CNM (12%) and DRMs (8%). Weiss et al. showed that the most common type was CFTD (37%), MTM (28%), NM (20%), and CCD (14%). Nonaka et al. showed the most common type was NM (27%), CFTD (20%), MTM (16%), CCD (6%), and CM without specific features (7%). The relative proportion of various types of CMs in our series is different from other series. However, this study was of a shorter duration with fewer patients.
The age at diagnosis ranged from newborn to 35-year-old with a mean age of 7.5 years. Of 11 biopsy-proven cases, 4 patients had CFTD (2 males and 2 females). One patient [Case 1] presented at birth with inability to close eye and mouth completely. All the four patients presented with delayed motor milestones. The majority of patients with CFTD as described by Brooke et al. had congenital onset hypotonia, shot stature, joint contractures, and skeletal deformities with high arched palate. There is generally sparing of pharaynx, ocular, and facial muscles. One of our patients [Case 2] presented at the age of 12 years with a history of proximal weakness in bilateral upper and lower limbs and history of recurrent falls. He had prominent scapular winging and high arched palate with calf hypertrophy and ankle contractures. In one patient [Case 3], there was antenatal history of reduced fetal movements in third trimester. All patients had generalized hypotonia. [Case 4] had dolicocephaly and kyphosis with high arched palate. There was wasting of bilateral temporalis muscle. There were generalized wasting and contracture around elbow, knee, and ankle. Patient of CFTD as described by Jain et al. also had presentation at birth with dysmorphic feature and delayed motor milestones, proximal weakness without any specific muscle hypertrophy or wasting. They had described, drooping eyelids since birth in a 8-year-old male. One of our patients also had inability to close eyes and mouth since birth. The additional feature presented in our patient with CFTD was bilateral scapular winging with calf hypertrophy and in other patients there was wasting of bilateral temporalis muscle. In a series of CFTD as described by Weiss et al., all of their patients presented with hypotonia and muscle weakness before 4 months of age. Facial weakness and high arched palate were also have been reported and some of their patients develop respiratory insufficiency severe enough requiring mechanical ventilation. Sharma et al. reported a case series of 4 patients with CFTD, two of the patients presented with a history of delayed motor milestones. Facial dysmorphism with ptosis was present in two of the patients. The patients who had ptosis also had high arched palate. Two patients [Cases 5 and 6] the histopathological diagnosis was CNM. [Case 5], a 28-year-old male, preterm delivered, presented with a history of delayed motor milestones and difficulty in walking and running with frequent falls. He had high arced palate with elongated facies and generalized hypotonia. The striking feature in this patient was wasting of bilateral quadriceps muscle. His EMG was myopathic and CK was normal. Another patient, [Case 6] 19-year-old female, presented with 9½ years history of distal >> proximal weakness in both LL and proximal weakness in bilateral upper limb with truncal weakness. She had bilateral foot drop, pes cavus and hammer toe with dorsal scoliosis. She was having mild bilateral facial weakness. The peculiar feature in her was that she had bilateral scapular winging and her bilateral EDB was prominent with areflexia. In one series of three patients of CNMas described by Jain et al., the patients presented with difficulty in walking and running with hypotonia and skeletal deformities. Two of these patients had facial dysmorphism and one patient had low set ears. The description of CNM as per Wallgren-Pettersson et al. include patients who had presented with hypotonia, bulbar, and facial weakness with ophthalmoplegia and respiratory distress. There can be proximal weakness and skeletal deformities. Patient can present with bilateral foot drop, knee, and ankle contractures. Patients of CNM as described by Weiss et al., the most common finding was of facial muscle weakness, followed by breathing difficulty and high arched palate. They also reported contractures and skeletal deformities in few of his patients. One of our patient [Case 7], a 31-year-old female, who presented with a history of delayed motor milestones and a 5-year history of progressive drooping of eyelids with dysphagia and nasal intonation of voice. She had bilateral ptosis, external ophthalmoplegia, high arched palate and there was a history of frequent RTI in the past. In view of her complaints and progressive course, clinical possibility of mitochondrial cytopathy was also discussed. She also had bilateral temporalis muscle wasting. Histopathology was suggestive of CCD. CCD usually presented in infancy with weakness and hypotonia. Patient presented with delayed motor milestones, proximal weakness, and skeletal deformities. CCD is also associated with an increased risk of malignant hyperthermia. Jain et al. described 6 patients of CCD, who generally present in their first decade of life with a history of frequent falls, difficulty in walking, and running with delayed motor milestones. Ocular and facial muscle involvement had not been described [Case 8], who was diagnosed as a case of DRM was a 20-year-old male presented with 12-year history of weakness in both lower limbs in the form of bilateral foot drop followed by proximal weakness. He also had proximal weakness in both upper limbs. He had kyphosis with wasting of bilateral infraspinatous, teres major, and quadriceps. He had hypertrophied bilateral EDB with tendo-achilli contractures. DRM as described by Jain et al., in one of the study had found presentation at an older age as compared with other patients of CM. One of the patients was thin, lean and had generalized weakness with wasting of muscles. Distal muscle weakness, cardiac involvement along with histopathological findings of rimmed vacuoles, and eosinophilic inclusion are typical for desminopathies. DRM as described by Sharma et al. usually manifest in second to fourth decade of life, characterized by slowly progressive distal muscle weakness and atrophy of the lower extremities. The weakness usually spreads from distal to truncal weakness, facial and respiratory muscles, and was also associated with cardiac abnormalities. Our patient also presented in second decade with distal weakness in the lower limbs in the form of bilateral foot drop and there was wasting of bilateral quadriceps muscle. One patient [Case 9] diagnosed as a case of CM with type II fiber hypoplasia presented with a history of delayed motor milestones. There was a history of proximal weakness with frequent falls. He had short stature, dolicocephaly, and cubitus varus deformity. Family history was negative and his course was non-progressive. This type of CM is not very common. Castro-Gago et al. described two patients of CM with type II fiber hypoplasia, one patient a 9-year-old boy presented with a history of hypotonia, gait disorder, and frequent falls while running. There was a negative family history and his antenatal history was uneventful. He presented with history delayed motor milestones, mild hypotonia, muscle hypotrophy mainly of proximal muscles with absent patellar and biceps reflexes with waddling gait. Second patient, a 3-year-old boy presented with a history of delayed motor milestones with frequent falls while walking. Family history was negative. There were hypotonia and hypotrophy of proximal muscles and a myopathic gait with accentuation of lumbar lordosis. He showed moderate Gower’s sign. Our patient also presented with a history of delayed motor milestones with frequent falls during walking and running with waddling gait and a negative family history. However, he had short stature, dolicocephaly, high arched palate, and skeletal deformities (cubitus varus). Deep tendon reflexes were normal. One patient as described by Yoshioka et al. was a 14-month-old boy with severe hypotonia, muscle weakness with delayed motor milestones. He had severe kyphoscoliosis. There were areflexia and the patient later developed right-side heart failure. Muscle biopsy revealed CM with type II fiber hypoplasia.
In our series, [Case 10] was a 1½-year-old male with normal antenatal and birth history, presented with a history of delayed motor milestones. Histopathology was suggestive of nemaline rod myopathy. NM as described in the literature, the typical congenital form usually presents in neonatal period or first year of life with hypotonia, weakness, and feeding difficulties. In study by Jain et al. of NM patient present at birth or in early childhood, with generalized hypotonia, difficulty in walking, running, feeding problem, and frequent chest infections. NM as described by Deepti et al. in a report of four cases, patients usually presented with weakness, hypotonia, elongated facies, and skeletal deformities.
The most common CM in our study was CFTD followed by CNM as compared with the study from South India which revealed CNM most common followed by CFTD, whereas another study from North India had described the most common CM to be CCD followed by NM. This is the third-largest series from India and in a short span of two years as compared to other two which are a 6-year and 25- year study
In one of our cases of CFTD, there was a prominent scapular winging and high arched palate with calf hypertrophy and ankle contractures, which is not described in the literature there was wasting of bilateral temporalis muscle. This clinical features closely resemble with muscular dystrophies which are usually not having a good prognosis and treatment, so that needs to be closely look for as if it turns out to be a CM it is having a fairly good prognosis.
The striking feature in CNM in our case was wasting of bilateral quadriceps muscle. Distal weakness is more than proximal weakeness. She was having mild bilateral facial weakness. The peculiar feature is bilateral scapular winging and her bilateral prominence of EDB, again an atypical finding in Centronuclear disease which needs to be differentiated from dystrophies as they were having guarded prognosis with limited treatment options.
CCD patients in our case presented symptoms resembling mitochondrial and myasthenic features and that too in a later age group again a rare finding coupled with bilateral temporalis muscle wasting. Prognosis is good as compared with other types.
CM with type 2 fiber hypoplasia is very rarely described from Indian literature, the Atypical findings were short stature, dolicocephaliny, high arched palate, and skeletal deformities.
The CMs at times resembles closely with the muscular dystrophies, a close observation, and clinical examination is warranted especially in overlap situations like in some cases of ours, because management options and long term prognosis is altogether different in such cases, as fairly better for CMs as most of our cases are doing well in follow-ups.
| Conclusion|| |
The CMs are a group of neuromuscular disorders characterized by early onset of muscular weakness with slow progression or nonprogression. The presentation is non-specific with close resemblance to spinal muscular atrophy, muscular dystrophies, and mitochondrial myopathies. Clinically, it is difficult to distinguish between various subtypes; however, presence of delayed motor milestones with high arched palate, proximal weakness, and skeletal deformities clinches toward the diagnosis. Electromyography aids in diagnosis and to exclude other neuromuscular disorders. The antenatal history of reduced fetal movements and nonprogressive symptoms usually aids in the diagnosis. Histopathology with immunohistochemistry and electron microscopy along with genetic study help in arriving at a final diagnosis. In histopathology, the specific feature to look for is the variation in fiber size, diameter, characteristically the central cores, central nuclei, and nemaline rods, rimmed vacuoles with eosinophilic inclusions. Usually a well preserved fascicular architecture and immunopositivity with various membrane and cytoplasmic proteins. There are only few studies in Indian literature describing CMs. This study from India highlights the importance of specific clinical features to look for when suspecting a CM coupled with specific features in histopathology. However, studies with longer duration are needed to find out the true prevalence and various spectra of CMs.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]