Ignite Creation Date:
2024-10-26 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 3:39 PM
Study NCT ID:
NCT06574919
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-08-12
Brief Title:
Clinical and Functional Assessment of Patients With Inherited Non-Duchenne Myopathies in Sohag University Hospital
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Clinical and Functional Assessment of Patients With Inherited Non-Duchenne Myopathies in Sohag University Hospital
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Muscular Myopathies are a heterogenous group of inherited muscular disorders characterized by progressive muscle weakness Historically these disorders are difficult to treat In the last three decades there is a great progress in molecular and genetic basis of these disorders early diagnosis is achievable with proper clinical recognition and advanced genetic testing 1
Duchenne Muscular Dystrophy DMD is a neuromuscular muscular X-linked recessive disorders that belong to a group of disorders known as dystrophinopathies DMD is caused by mutations in the dystrophin gene that placed in the middle of short arm of X chromosome 2 Mutation in this gene lead to absence of dystrophin or structural defects of this protein The lack of functional dystrophin impairs the structure and function of myofibers which are essential for physiological growth of muscle tissue 3
The non-dystrophic myopathies are a group of inherited myopathies defined by distinctive static histochemical andor characteristic ultrastructural changes on muscle
The nomenclature of dystrophic myopathies can be confusing as some of them are classified by age of onset of symptoms eg congenital muscular dystrophies whereas others are classified by distribution of weakness eg limb-girdle muscular dystrophies distal myopathies facioscapulohumeral dystrophy and oculopharyngeal muscular dystrophy by characteristic clinical features eg myotonic dystrophy by the name of the causative gene eg GNE-myopathy dystrophinopathies whereas others are named after the physician first describing the disease ie Duchenne and Becker muscular dystrophy or Bethlem myopathy or can be subdivided in an entirely different way ie the subgroups of the limb-girdle muscular dystrophies which were named according to their mode of inheritance and order of publication 4 Several aspects need to be taken into account in order to establish a clinical diagnosis these features include but are not limited to the severity of the muscular wasting as well as its distribution and the accompanying symptomology biochemical hematological physical and neurological investigations electromyography and muscle biopsy Moreover if the gene defect is established diagnosis can also be confirmed by gene testing 5
Muscle biopsy lacks of typical dystrophic features such as increased conjunctive endomysial tissue necrosis and regeneration and shows one or more characteristic histological features Based in pathological descriptions the main non-dystrophic myopathies were described during the last century taking into account the age of onset and the structural or ultrastructural markers 6
Certain genes in particular those with large sizes TTN RYR1 NEB may present with different clinical and histological phenotypes and therefore their related myopathies be classified within different groups 7
It is useful to know that other genetic myopathies may mimic non-dystrophic myopathies This is the case of certain metabolic and mitochondrial myopathies that may show very selective muscle weakness The description of these disorders goes beyond the scope of this chapter However it may be useful to take into account at least three examples Pompe disease the glycogen storage disorder type II GSD II and TK2-related mitochondrial DNA depletion myopathy because they may present as congenital or later-onset non-dystrophic myopathies may show particular muscle imaging abnormalities and may be treatable 8 9
Understanding the clinical and molecular characteristics of non-DMD is crucial for several reasons First accurate diagnosis is essential for proper genetic counseling and family planning Second identification of the specific genetic mutation allows for the potential development of targeted therapies in the future Finally characterization of the clinical course of different non-DMD can guide treatment decisions and improve patient outcomes
Duchenne Muscular Dystrophy DMD is a neuromuscular muscular X-linked recessive disorders that belong to a group of disorders known as dystrophinopathies DMD is caused by mutations in the dystrophin gene that placed in the middle of short arm of X chromosome 2 Mutation in this gene lead to absence of dystrophin or structural defects of this protein The lack of functional dystrophin impairs the structure and function of myofibers which are essential for physiological growth of muscle tissue 3
The non-dystrophic myopathies are a group of inherited myopathies defined by distinctive static histochemical andor characteristic ultrastructural changes on muscle
The nomenclature of dystrophic myopathies can be confusing as some of them are classified by age of onset of symptoms eg congenital muscular dystrophies whereas others are classified by distribution of weakness eg limb-girdle muscular dystrophies distal myopathies facioscapulohumeral dystrophy and oculopharyngeal muscular dystrophy by characteristic clinical features eg myotonic dystrophy by the name of the causative gene eg GNE-myopathy dystrophinopathies whereas others are named after the physician first describing the disease ie Duchenne and Becker muscular dystrophy or Bethlem myopathy or can be subdivided in an entirely different way ie the subgroups of the limb-girdle muscular dystrophies which were named according to their mode of inheritance and order of publication 4 Several aspects need to be taken into account in order to establish a clinical diagnosis these features include but are not limited to the severity of the muscular wasting as well as its distribution and the accompanying symptomology biochemical hematological physical and neurological investigations electromyography and muscle biopsy Moreover if the gene defect is established diagnosis can also be confirmed by gene testing 5
Muscle biopsy lacks of typical dystrophic features such as increased conjunctive endomysial tissue necrosis and regeneration and shows one or more characteristic histological features Based in pathological descriptions the main non-dystrophic myopathies were described during the last century taking into account the age of onset and the structural or ultrastructural markers 6
Certain genes in particular those with large sizes TTN RYR1 NEB may present with different clinical and histological phenotypes and therefore their related myopathies be classified within different groups 7
It is useful to know that other genetic myopathies may mimic non-dystrophic myopathies This is the case of certain metabolic and mitochondrial myopathies that may show very selective muscle weakness The description of these disorders goes beyond the scope of this chapter However it may be useful to take into account at least three examples Pompe disease the glycogen storage disorder type II GSD II and TK2-related mitochondrial DNA depletion myopathy because they may present as congenital or later-onset non-dystrophic myopathies may show particular muscle imaging abnormalities and may be treatable 8 9
Understanding the clinical and molecular characteristics of non-DMD is crucial for several reasons First accurate diagnosis is essential for proper genetic counseling and family planning Second identification of the specific genetic mutation allows for the potential development of targeted therapies in the future Finally characterization of the clinical course of different non-DMD can guide treatment decisions and improve patient outcomes
Detailed Description:
Type of the study
This study will be a prospective observational study
Place of the study
Pediatric Neurology Clinic and Genetics Unit Department of pediatrics Sohag University Hospital Sohag Egypt
Study duration
One year starting from obtaining approval from the research ethics committee
Study Population
Children diagnosed with non-DMD at Sohag University Hospital will be included in the study
Inclusion criteria
Age between 2 and 18 years
Confirmed diagnosis of non-DMD based on clinical features laboratory investigations and genetic testing
Patients and their parents agree to participate in the study
Exclusion criteria
Children with a confirmed diagnosis of DMD
Children with incomplete medical records or unavailable clinical data
Children with endocrinal nutritional critical care and inflammatory myopathies
Other neuromuscular disorders that affect AHC or nerves as SMA congenital myasthenia Gravis and neuropathic
Other acquired neuromuscular disorders as Guillain Barre syndrome and toxic myopathy
Patients and their parents refuse to participate in the study
This study will be a prospective observational study
Place of the study
Pediatric Neurology Clinic and Genetics Unit Department of pediatrics Sohag University Hospital Sohag Egypt
Study duration
One year starting from obtaining approval from the research ethics committee
Study Population
Children diagnosed with non-DMD at Sohag University Hospital will be included in the study
Inclusion criteria
Age between 2 and 18 years
Confirmed diagnosis of non-DMD based on clinical features laboratory investigations and genetic testing
Patients and their parents agree to participate in the study
Exclusion criteria
Children with a confirmed diagnosis of DMD
Children with incomplete medical records or unavailable clinical data
Children with endocrinal nutritional critical care and inflammatory myopathies
Other neuromuscular disorders that affect AHC or nerves as SMA congenital myasthenia Gravis and neuropathic
Other acquired neuromuscular disorders as Guillain Barre syndrome and toxic myopathy
Patients and their parents refuse to participate in the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None