Patient case (clinical description): An 8-year-old boy is brought to the clinic by his parents because of weakness and difficulty of standing up from a sitting position. The mother is healthy but had a brother who died in his 20th after being disabled and using wheelchairs in the last few years of his life. Physical examination shows 3/5 lower extremity muscle strength and enlarged calf muscles. The other physical examination and vital signs are unremarkable. Muscle biopsy showed absence of dystrophin protein. The patient is diagnosed with DMD.

Patient's own account: I brought my  8-year-old son to the doctor's clinic. He was struggling to stand up from a chair for the past few days. My wife is healthy but she was pretty worried since his brother died in his 20s after being disabled and using a wheelchair for the last years of his life. The doctor did an exam which highlighted weakness in the leg muscles and unusually large calf muscles. The rest of the exam was fine, and his vitals were normal. My son did a muscle biopsy, and it showed that the protein important for muscle strength and function is missing. The doctor diagnosed him with Duchenne muscular dystrophy.

Clinical trial: Multi-center Clinical Study on the Diagnosis and Treatment Management of Rare Neurological Disease in Children

Eligibility criteria:
1. SMA:

        Inclusion criteria: patients meet the all the following criteria:

          1. Clinically manifestation: hypotonia, progressive symmetric and proximal weakness
             affecting the legs more than the arms, sparing of the facial muscles but often with
             bulbar muscle weakness.

          2. Neurogenic EMG. EMG is also usually not needed in type 1 and 2 children; this
             investigation can help in more chronic forms in which the phenotype might be less
             striking.

          3. Along with EMG and NCV test, a muscle or nerve biopsy can be used to diagnose spinal
             muscular atrophy if molecular genetic testing of SMN1 does not identify mutations.

          4. Genetic testing of SMN1/SMN2: Homozygous absence of exons 7 and 8 of the SMN1
             gene(96%), or only of exon 7, or other mutations. SMN2 copy numbers may vary. Genetic
             testing is the gold standard of diagnosis.

        Exclusion Criteria: None.

        -

        2. DMD:

        Inclusion criteria: patients meet the all the following criteria:

          1. Clinically manifestation: weakness, clumsiness, a Gowers' sign, difficulty with stair
             climbing, or toe walking. developmental delay or increased concentrations of serum
             enzymes such as alanine aminotransferase, aspartate aminotransferase, lactate
             dehydrogenase, or very high creatine kinase level.

          2. Dystrophin gene mutation: dystrophin gene deletion and duplication testing is usually
             the first confirmatory test best done by MLPA or comparative genomic hybridisation
             array. Approximately 70% of individuals with DMD have a single-exon or multi-exon
             deletion or duplication in the dystrophin gene. If deletion or duplication testing is
             negative, genetic sequencing should be done to screen for the remaining types of
             mutations that are attributed to DMD (approximately 25-30%).

          3. Muscle biopsy: if genetic testing does not confirm a clinical diagnosis of DMD, then a
             muscle biopsy sample should be tested for the presence of dystrophin protein by
             immunohistochemistry of tissue cryosections or by western blot of a muscle protein
             extract. Muscle samples from DMD patient has no dystrophin present, while BMD Becker
             muscular dystrophy (with some partially functional dystrophin present).

        Exclusion Criteria: None. -

        3. X-ALD:

        Inclusion criteria: patients meet the all the following criteria:

        1. Clinically manifestation:

          1. Attention deficit disorder or hyperactivity; progressive impairment of cognition,
             behavior, vision, hearing, and motor function follow the initial symptoms and often
             lead to total disability within six months to two years.

          2. Adrenomyeloneuropathy (AMN) manifests as progressive stiffness and weakness of the
             legs, sphincter disturbances, sexual dysfunction, and often, impaired adrenocortical
             function; all symptoms are progressive over decades, most commonly in an individual in
             his twenties or middle age.

          3. Magnetic resonance imaging shows cerebral demyelination.

        2. Dystrophin gene mutation: The diagnosis of X-ALD is usually established in a female
        proband with detection of a heterozygous ABCD1 pathogenic variant and elevated VLCFA.

        Exclusion Criteria: None. -

        4. TSC:

        Inclusion criteria:patients meet the all the following criteria:

        A. Clinical diagnostic criteria:

          1. Major features: (1) Hypomelanotic macules (≥3, at least 5-mm diameter). (2)
             Angiofibromas (≥3) or fibrous cephalic plaque. (3) Ungual fibromas (≥2). (4) Shagreen
             patch. (5) Multiple retinal hamartomas. (6) Cortical dysplasias. (7) Subependymal
             nodules. (8) Subependymal giant cell astrocytoma. (9) Cardiac rhabdomyoma. (10)
             Lymphangioleiomyomatosis (LAM). (11) Angiomyolipomas (≥2).

          2. Minor features: (1)"Confetti" skin lesions. (2) Dental enamel pits (>3). (3) Intraoral
             fibromas (≥2). (4) Retinal achromic patch. (5) Multiple renal cysts. (6) Nonrenal
             hamartomas.

        Two major features or one major feature with ≥2 minor features can diagnose. Either one
        major feature or ≥2 minor features can diagnosis possibly.

        B. Genetic diagnostic criteria:

        The identification of either a TSC1 or TSC2 pathogenic mutation in DNA from normal tissue
        is sufficient to make a definite diagnosis of TSC.

        Exclusion Criteria: None.

        -
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.

Subject must be at most 18 Years

Eligibility (NLI label): Entailment