Podcast
Questions and Answers
Which gene is primarily affected in Spinal Muscular Atrophy (SMA)?
Which gene is primarily affected in Spinal Muscular Atrophy (SMA)?
- SMN 1 gene (correct)
- SMN 3 gene
- SMN 2 gene
- SMN 4 gene
Hypotonia in SMA is characterized by normal muscle tone.
Hypotonia in SMA is characterized by normal muscle tone.
False (B)
What is the primary consequence of increased apoptosis of motor neurons in SMA?
What is the primary consequence of increased apoptosis of motor neurons in SMA?
Hypotonia and flaccidity of muscles
The _____ type of weakness is characteristic of Spinal Muscular Atrophy.
The _____ type of weakness is characteristic of Spinal Muscular Atrophy.
Match the clinical features of SMA with their descriptions:
Match the clinical features of SMA with their descriptions:
What is the primary cause of neurocysticercosis?
What is the primary cause of neurocysticercosis?
Neurocysticercosis can be diagnosed using a blood test.
Neurocysticercosis can be diagnosed using a blood test.
What is a common clinical presentation of neurocysticercosis involving the brain?
What is a common clinical presentation of neurocysticercosis involving the brain?
Treatment for single cysts in neurocysticercosis includes the medication __________ for 10-14 days.
Treatment for single cysts in neurocysticercosis includes the medication __________ for 10-14 days.
Match the treatment methods with their respective purposes:
Match the treatment methods with their respective purposes:
What is the most common worldwide cause of Japanese Encephalitis?
What is the most common worldwide cause of Japanese Encephalitis?
The primary vector for Japanese Encephalitis is the Culex tritaeniorhynchus mosquito.
The primary vector for Japanese Encephalitis is the Culex tritaeniorhynchus mosquito.
What is the first-line treatment for Herpes Simplex Encephalitis?
What is the first-line treatment for Herpes Simplex Encephalitis?
Japanese Encephalitis primarily affects ______ children.
Japanese Encephalitis primarily affects ______ children.
Match the following features with their associated conditions:
Match the following features with their associated conditions:
What is the most common cause of congenital hypothyroidism?
What is the most common cause of congenital hypothyroidism?
Goitre is commonly present in cases of thyroid dysgenesis.
Goitre is commonly present in cases of thyroid dysgenesis.
Name one feature of congenital hypothyroidism that can be observed after the first week of life.
Name one feature of congenital hypothyroidism that can be observed after the first week of life.
In cases of thyroid dyshormonogenesis, one common defect is __________ deficiency.
In cases of thyroid dyshormonogenesis, one common defect is __________ deficiency.
Match the following investigations with their results in congenital hypothyroidism:
Match the following investigations with their results in congenital hypothyroidism:
What is the primary consequence of decreased gonadotropins in children with hypopituitarism?
What is the primary consequence of decreased gonadotropins in children with hypopituitarism?
Prolonged jaundice is a common symptom associated with Growth Hormone Deficiency.
Prolonged jaundice is a common symptom associated with Growth Hormone Deficiency.
What is the recommended treatment for Growth Hormone Deficiency?
What is the recommended treatment for Growth Hormone Deficiency?
The most common preventable cause of intellectual disability is __________.
The most common preventable cause of intellectual disability is __________.
Match the conditions with their respective treatments or management:
Match the conditions with their respective treatments or management:
What is the most common cause of Growth Hormone Deficiency?
What is the most common cause of Growth Hormone Deficiency?
Laron's Dwarfism is caused by an overproduction of GH receptors.
Laron's Dwarfism is caused by an overproduction of GH receptors.
What is a characteristic feature of Isolated Growth Hormone Deficiency?
What is a characteristic feature of Isolated Growth Hormone Deficiency?
The pathology of Laron's Dwarfism primarily involves defective _____ receptors.
The pathology of Laron's Dwarfism primarily involves defective _____ receptors.
Match the following terms with their descriptions:
Match the following terms with their descriptions:
What is the mode of inheritance for Myotonic Dystrophy Type 1?
What is the mode of inheritance for Myotonic Dystrophy Type 1?
Myotonic Dystrophy Type 1 is caused by a defect in the DMPK gene located on chromosome 19.
Myotonic Dystrophy Type 1 is caused by a defect in the DMPK gene located on chromosome 19.
Name one clinical feature of Myotonic Dystrophy Type 1 related to facial appearance.
Name one clinical feature of Myotonic Dystrophy Type 1 related to facial appearance.
Individuals with Myotonic Dystrophy Type 1 commonly experience _____ in their limb muscles.
Individuals with Myotonic Dystrophy Type 1 commonly experience _____ in their limb muscles.
Match the following clinical features with their corresponding descriptions:
Match the following clinical features with their corresponding descriptions:
What is the characteristic gait associated with proximal muscle weakness in neuromuscular disorders?
What is the characteristic gait associated with proximal muscle weakness in neuromuscular disorders?
Calf muscle pseudo hypertrophy is a typical feature in the early stages of neuromuscular disorders.
Calf muscle pseudo hypertrophy is a typical feature in the early stages of neuromuscular disorders.
At what age does proximal muscle weakness typically occur in children with neuromuscular disorders?
At what age does proximal muscle weakness typically occur in children with neuromuscular disorders?
The major cause of death in individuals with neuromuscular disorders is due to cardiac and __________ muscle insufficiency.
The major cause of death in individuals with neuromuscular disorders is due to cardiac and __________ muscle insufficiency.
Match each investigation with its description:
Match each investigation with its description:
What is the most common cause of morbidity/mortality in Spinal Muscular Atrophy (SMA)?
What is the most common cause of morbidity/mortality in Spinal Muscular Atrophy (SMA)?
Duchenne Muscular Dystrophy (DMD) is an autosomal dominant condition.
Duchenne Muscular Dystrophy (DMD) is an autosomal dominant condition.
What is the primary mechanism of action for Zolgensma in treating SMA?
What is the primary mechanism of action for Zolgensma in treating SMA?
The _____ type of muscular dystrophy is caused by a mutation in the dystrophin gene.
The _____ type of muscular dystrophy is caused by a mutation in the dystrophin gene.
Match the clinical types of SMA with their lifespan:
Match the clinical types of SMA with their lifespan:
Which type of muscular dystrophy is characterized by late onset muscle weakness around the age of 5 years?
Which type of muscular dystrophy is characterized by late onset muscle weakness around the age of 5 years?
Facioscapulohumeral Dystrophy is inherited in an autosomal recessive manner.
Facioscapulohumeral Dystrophy is inherited in an autosomal recessive manner.
What are the defective proteins associated with Limb Girdle Muscular Dystrophy?
What are the defective proteins associated with Limb Girdle Muscular Dystrophy?
In Becker Muscular Dystrophy, individuals may have a longer lifespan until the age of ___ years.
In Becker Muscular Dystrophy, individuals may have a longer lifespan until the age of ___ years.
Match the types of muscular dystrophy with their characteristics:
Match the types of muscular dystrophy with their characteristics:
Flashcards are hidden until you start studying
Study Notes
Spinal Muscular Atrophy (SMA)
- Autosomal recessive disorder caused by a mutation in the SMN1 gene on chromosome 5q.
- The SMN1 gene codes for the SMN protein, which protects motor neurons from apoptosis.
- A defective SMN1 gene leads to increased motor neuron apoptosis, resulting in muscle weakness and hypotonia.
- Two types of SMN genes: SMN1 and SMN2.
- SMN1 produces a fully functional protein, while SMN2 produces a dysfunctional protein due to the absence of exon 7.
- SMN1 is the primary gene affected in SMA; SMN2 is a backup gene.
- Hypotonia is a hallmark of SMA, especially Type 1, characterized by:
- Frog leg posture
- Decreased or absent spontaneous limb movements
- No resistance to passive flexion
- Ragged doll appearance
- Lower motor neuron (LMN) type of weakness with:
- Decreased or absent deep tendon reflexes (DTR)
- Disuse atrophy of muscles
- Extraocular muscles are not involved in SMA, but are affected in myasthenia gravis.
- Other classic signs of SMA include:
- Tongue fasciculations
- Normal mentation
- A characteristic frog-like posture in infants with flexed thighs and extended legs.
Neurocysticercosis
- A neurological infection caused by the larval stage of the pork tapeworm Taenia solium.
- Transmitted via ingestion of undercooked pork or contaminated food.
- Presents acutely with encephalitis:
- Fever
- Altered sensorium
- Seizures (focal or generalized epilepsy, recent onset)
- Cysts in the brain can be visualized through brain imaging (CT or MRI):
- Single cyst with surrounding edema: Often presents as epilepsy
- Multiple cysts plus perilesional edema: Exhibits a "starry sky" appearance
- Treatment:
- Steroids: Dexamethasone (within 148 hours of diagnosis) to reduce inflammation
- Anti-epileptics:
- Oxcarbazepine (focal epilepsy) for 6 months
- Sodium valproate (general epilepsy) for 6 months
- Cysticidal therapy:
- Albendazole (10-14 days) for single cysts
- Praziquantel (for multiple cysts)
Japanese Encephalitis (JE)
- Caused by Japanese Encephalitis virus, the most common cause of encephalitis worldwide.
- Herpes Simplex virus (HSV) is the most common cause of sporadic encephalitis.
- Vector: Culex tritaeniorhynchus (Culex mosquito)
- Host: Ticks (amplifier host), birds
- Most commonly affects school-going children.
- Diagnosis:
- Polymerase Chain Reaction (PCR)
- Cerebrospinal Fluid (CSF) analysis:
- Increased lymphocytes
- Normal sugar
- Slightly elevated protein
- Imaging:
- Target areas: Basal ganglia > Thalamus
- Management:
- Supportive treatment
- Prevention:
- JE vaccine
Herpes Simplex Encephalitis
- Characterized by:
- Fever
- Focal seizures
- Focal neurological deficits (e.g., aphasia, speech defects)
- Behavioral disturbances
- Movement disorders
- Investigations:
- CSF analysis:
- Increased lymphocytes
- Normal sugar
- Slightly elevated protein
- PCR
- Imaging
- EEG
- Target areas: Temporal lobe
- Characteristic finding: Periodic Lateralizing Epileptiform Discharges (PLED)
- CSF analysis:
- Treatment:
- Intravenous Acyclovir (DOC): 14-21 days
Endocrine System - Hypothyroidism
- Classified based on the pathology:
- Primary: Thyroid gland pathology
- Central: CNS pathology
- Hypothalamus
- Pituitary
- Etiology:
- Anomaly: Thyroid dysgenesis
- Most common cause
- Sporadic
- Thyroid dyshormonogenesis: Defects in organification
- Most common type
- Peroxidase deficiency
- Autosomal recessive inheritance
- Severe Iodine deficiency: Endemic goitre/cretinism
- Seen in underdeveloped countries
- Maternal causes:
- Transplacental transfer of maternal antibodies: TSH
- Receptor blocking antibody
- Antithyroid drugs
- Anomaly: Thyroid dysgenesis
- Difficult to identify in newborns (first week) due to maternal hormone masking.
- Features after one week include:
- Decreased activity
- Wide open posterior fontanelle (>5 mm)
- Cold, dry skin
- Constipation/delay in passing meconium
- Macroglossia
- Umbilical hernia
- Hoarse cry
- Prolonged jaundice
- Goitre (usually absent in thyroid dysgenesis, present in dyshormonogenesis and maternal antithyroid drug usage)
- Investigations:
- Thyroid Function Test (TFT):
- Decreased T3
- Decreased free T4
- Increased TSH
- Screening: Heel prick dried blood spot testing for all infants
- Thyroid Function Test (TFT):
Myotonic Dystrophy Type 1
- Mode of inheritance: Autosomal dominant
- Trinucleotide repeats: CTG > 80 (Normal < 35)
- Defective gene: DMPK gene on chromosome 19
- Clinical features:
- HATCHET Facies:
- Early manifestations:
- Ptosis
- Inverted V appearance of the upper lip
- Late manifestations:
- Temporal hollowing
- Thinning of cheek area
- Early manifestations:
- Myotonia:
- Delayed relaxation of muscles
- Inferred by:
- Shaking hands
- Difficulty in letting go of hand
- Percussion at the base of the thumb
- Limb weakness:
- Distal muscles affected:
- Retarded purposeful movements with hands
- Flattened thenar and hypothenar eminences
- Weak foot muscles: Foot drop, abnormal gait
- Distal muscles affected:
- Other features:
- Posterior capsular cataract
- Endocrinopathies:
- Hyperinsulinism
- Testicular atrophy
- Adrenal gland atrophy
- HATCHET Facies:
Growth Hormone Deficiency
- Most common cause: Idiopathic
- Types:
- Isolated
- Congenital:
- Developmental:
- Ectopic pituitary
- Septo-optic dysplasia
- Genetic mutations:
- GH gene
- GHRH receptor gene
- Developmental:
- Acquired:
- Trauma
- Tumor:
- Craniopharyngioma
- Germinoma
- Histiocytosis
- Sarcoidosis
- Infiltration
- Irradiation
- Laron's Dwarfism:
- Due to hypopituitarism
- Pathogenesis: Defective GH receptor (resistance to the effect of GH)
- Defective GH receptors on the liver
- Reduced release of IGF-1
- Characteristic feature: Low levels of IGF-1
- Features of Isolated GH Deficiency:
- Normal at birth (no role of GH during fetal life)
- Proportionate short stature during infancy
- Decreased growth velocity (<4 cm/yr)
- Doll-like appearance
- Delayed bone age
- Mid-parental height (MPH) < -2 SD from MPH
- Decreased GH → decreased lipolysis → Fat deposition
- Prominent cheeks
- Overweight/obese
Hypothyroidism
- Thyroid gland is essential for brain development, so early detection (within the first two years) is crucial.
- Undected and untreated hypothyroidism can lead to intellectual disability.
- Congenital Hypothyroidism: Most preventable cause of intellectual disability.
- Growth Hormone Deficiency & Hypothyroidism - Note:
- If associated with hypopituitarism:
- Decreased gonadotropins → Decreased testosterone and other sex hormones → Micropenis and small testes → Delayed puberty
- Decreased ACTH → Decreased cortisol → Hypoglycemia
- Prolonged jaundice
- If associated with hypopituitarism:
Investigations for Growth Hormone Deficiency
- Screening:
- IGF-I levels (Malnutrition can alter IGF levels)
- Confirmatory:
- GH estimation: Stimulative/provocative GH testing (Random estimation is unreliable as GH is released in a pulsatile manner)
- Provocative substances: Insulin, clonidine, arginine
- GH < 10 ng/ml after test: Diagnostic
Treatment for Growth Hormone Deficiency
- Recombinant GH (rGH) given via subcutaneous injection, usually at night, until epiphyseal closure.
- Other uses of rGH:
- GTCS in Prader-Willi syndrome
- GH deficiency
- Turner syndrome
- Chronic Kidney Disease (CKD)
- Small for gestational age (SGA) > 2 years, SHOX gene mutation
- Idiopathic
- Noonan syndrome
- Prader-Willi syndrome
Becker Muscular Dystrophy
- Mild allelic (less severe) variant of Duchenne Muscular Dystrophy (DMD).
- Affected gene: Dystrophin gene.
- Late onset muscle weakness (~5 years).
- Slow progression of symptoms → Longer lifespan: Till 40 years.
- Early onset cardiomyopathy (compared to DMD).
Facioscapulohumeral Dystrophy
- Mode of inheritance: Autosomal dominant.
- Defective gene: FSHD1 (Facioscapulohumeral dystrophy).
- Clinical features: Muscle weakness
- Facial:
- Defective eye closure
- Rounded mouth
- Puckering of lips
- Humeral:
- Weakness of arm muscles
- Scapular:
- Forearm muscles normal: Popeye appearance
- Facial:
Limb Girdle Muscular Dystrophy
- Mode of inheritance: Autosomal recessive (most common in children) and autosomal dominant (most common in adults).
- Defective proteins: Caveolin 3, Calpain 3 (Cytoskeletal proteins)
- Clinical features:
- Affected areas: Shoulder girdle and hip girdle
- Neck and bulbar muscles are not affected
- Cardiac muscle involvement is rare
- Normal IQ
Neuromuscular Disorders
- Early features: Delay in attaining motor milestones
- Borderline low IQ (intellectual disability)
- Proximal muscle weakness:
- Occurs between 3-4 years of age.
- Hip: Waddling gait, Gower's sign (characteristic but not diagnostic)
- Shoulder and hip muscles affected
- Distal muscles (hands, feet) are not affected
- Calf muscle pseudo hypertrophy
- Plateauing of illness: Between 4–6 years of age.
- Progression:
- Dangerous manifestation:
- Spine muscles: Scoliosis and lordosis
- Bulbar muscles: Dysfunction of pharyngeal/laryngeal muscles
- Cardiac and respiratory muscle insufficiency: Leading cause of death (usually between 20-25 years of age)
- Dangerous manifestation:
- Investigations:
- Serum Creatinine kinase: 10 times the normal value.
- Gene testing: Diagnostic
- Multiple PCR
- Multiplex Ligand-dependent Probe Amplification (MLPA)
- Muscle biopsy
- Management:
- Incurable
- Steroids: Reduce the apoptosis rate
- Deflazacort
- Prednisolone
- Nerve treatment:
- Exon skipping therapy (AON): Eteplisren
- Ataluren: Suppress nonsense mutation
Duchenne Muscular Dystrophy (DMD)
- Most common type of neuromuscular disorder (NMD)
- Mode of inheritance: X-linked recessive (Xp)
- Mutated gene: Dystrophin gene (most common: nonsense mutation)
- Dystrophin protein:
- Cytoskeletal protein in muscle
- Promotes stabilization of muscle fibers
- Coordinates muscle contraction
- Mechanism of absence of dystrophin protein:
- Muscle instability
- Muscle weakness
- Premature apoptosis of muscle fibers
- Repair process
- Fibrous fatty deposition
Clinical Types of SMA (Based on Severity)
| Type | Age of Onset | Motor Milestones | Lifespan |
|---|---|---|---|
| 0 (Fatal) | Antenatal (< 6 months) | - | Few weeks |
| 1 (Werdnig-Hoffman disease) | < 6 months | Up to head control | < 2 years |
| 2 (Dubowitz disease) | < 18 months | Up to sitting independently (Cannot stand/walk) | 2nd - 3rd decade |
| 3 (Kugelberg-Welander disease) | > 18 months | Stand, walk (Partially ambulant) | Normal |
| 4 | Adolescence/adult | Fully ambulant | Normal |
Management of SMA
- Not a curable condition.
- Recent advances:
- Drug | Therapy | Mechanism of action | |---|---|---| | Zolgensma | Gene therapy: SMN gene incorporated with vector (Adenovirus) | SMN gene incorporates with an RNA vector.| | Nusinersen (Antisense oligonucleotide: AON) | Exon skipping therapy | Binds to the defective exon 7 area, producing a partially functioning protein.| | Risdiplam | | Includes exon 7 into a defective area of the gene.|
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
