Master Karthik, a 5 month old boy, 2nd order child of non-consanguineous marriage from Coimbatore, Tamil Nadu presented with complaints of inability to hold head, generalized floppiness since 2 months of age, progressive weakness of all four limbs, weak cry with difficulty in feeding, and fast effortful breathing since 4 weeks.

HOPI

• The infant was reportedly normal at birth and roomed-in successfully, but from 2 months of age the mother noticed he felt unusually soft and limp while holding him, slipping through her hands during vertical holding. Since this is an infantile hypotonia case, I would like to start the history from antenatal period with emphasis on fetal movements and perinatal course.

• Antenatal
  • Mother Mrs. Revathi, 28 years, $G_2 P_1 L_1$. Registered at 8 weeks at GH
  • 6 antenatal visits. Received 2 doses of Td and regular IFA/calcium
  • Normal scans at 12 and 20 weeks
  • Quickening at 18 weeks, but fetal kick counts were perceptibly weaker than during her first pregnancy (weak fetal movements suggest anterior horn cell disease)
  • No maternal fever with rash, GDM, GHTN, radiation exposure, or sedative intake
• Natal history
  • Delivered at 39 weeks + 2 days by NVD at a tertiary hospital. Clear liquor. Birth weight 2.9 kg (50th percentile, AGA)
  • Cried immediately. Apgar 8/1 min, 9/5 min. No resuscitation required
  • Roomed-in within 1 hour. Exclusive breastfeeding initiated successfully
  • Discharged on day 3 with normal neonatal checkup
  • No neonatal jaundice, hypoglycemia, seizures, or ventilation requirement
• Postnatal course
  • Around 6–8 weeks, legs remained flat on bed in abducted externally rotated posture (frog-leg posture)
  • By 2.5 months, spontaneous anti-gravity movements of lower limbs decreased; by 3 months upper limbs also involved
  • Weakness progressed over 4 weeks — proximal > distal, lower limbs > upper limbs, bilaterally symmetrical
  • Distal finger and toe movements preserved; cannot lift arms or legs off the bed
  • Feeding duration increased from 15–20 minutes to 45–60 minutes per feed with rest pauses and fatigue
  • Milk dribbling from corners of mouth, occasional coughing and choking during feeds
  • Cry became feeble, high-pitched and raspy over last month
  • Over past 4 weeks — paradoxical inward chest movement on inspiration with abdominal bulging; chest appears narrow above and flared below
  • Mother noticed fine tremulous movements of tongue and fingers during quiet rest (fasciculations — pathognomonic of anterior horn cell disease)
  • Child remains bright-eyed, tracks objects 180°, smiles responsively, recognizes mother — sensorium fully preserved throughout
• Milestones

• Gross motor $DQ = \frac{1.5 \text{ months}}{5 \text{ months}} \times 100 = 30\%$ — severe motor delay
• Social/cognitive $DQ = \frac{5 \text{ months}}{5 \text{ months}} \times 100 = 100\%$ — preserved
• Developmental dissociation: severe gross motor delay with normal social, visual and language milestones (selective motor delay localizes to peripheral motor unit, not cerebral cortex)
• Cranial nerve
  • Fixates and tracks objects in all directions. No ptosis, ophthalmoplegia or nystagmus (2,3,4,6 CN intact)
  • Weak masseter contraction; prolonged weak suck with nasal regurgitation (5th CN — bulbar weakness)
  • Symmetrical facial expression on smiling/crying (7th CN)
  • Turns head to sound but cannot lift head against gravity (8th CN hearing intact; 11th CN weak)
  • Weak cry, sluggish gag, pooling of secretions in posterior pharynx (9th and 10th CN)
  • Tongue fasciculations noted by mother at rest (12th CN — anterior horn cell involvement)
• No history of perinatal asphyxia, delayed cry, or NICU stay (rules out HIE / dyskinetic CP)
• No diurnal variation in weakness or eye drooping (rules out congenital myasthenic syndromes)
• No honey ingestion or preceding constipation (rules out infantile botulism)
• No dark urine, muscle pain, or hypertonia/clonus (rules out metabolic myopathy and central spasticity)
• No seizures, eye-rolling, or loss of previously acquired non-motor skills (rules out encephalopathy and neuroregression)
• No organomegaly, coarse facies, or macroglossia (rules out Pompe disease and storage disorders)
• No fixed contractures at birth or limb fractures (rules out arthrogryposis and osteogenesis imperfecta)
• No fever, chest retractions with infection, or umbilical sepsis (rules out sepsis-induced hypotonia at presentation)
• No cataracts, chorioretinitis, or dysmorphic features (rules out congenital infections and chromosomal syndromes)

Past History

• No previous hospital admissions
• No blood transfusion, drug allergies, or surgeries

Family history

• 2nd order child born of non-consanguineous marriage
• 1st child — female, 3 years, healthy and developing normally
• No history of floppy babies, early infant deaths, muscle diseases, or neuromuscular disorders in the family

% Karthik — Spinal Muscular Atrophy Type 1
I1 M UAf [label:Father]
I2 F UAf [label:Mother]
II1 F UAf 3y [label:Sister|Healthy]
II2 M Af 5m index [label:Karthik|SMA Type 1]

~ I1-I2 > II1,II2

Immunization history

• Immunized for age as per NIS — BCG, HBV birth dose, OPV0-2, Pentavalent 1-2, fIPV1, PCV1-2, Rota 1-2
• No optional vaccines were given
• No adverse events following immunization

Dietary history

The expected calories and proteins should be calculated from the ideal body weight, not from current weight.

• Exclusively breastfed till 3.5 months; now direct BF supplemented with EBM via paladai due to feeding fatigue (45–60 min/feed)
• Estimated intake ~110 kcal/kg/day — borderline inadequate; weight gain velocity slowing over last month
• Swallowing assessment pending; aspiration risk increasing with bulbar weakness

Socioeconomic and KAP

• Family from Coimbatore, lower middle class by modified Kuppuswamy scale
• Parents understand the child has progressive weakness; willing for genetic testing and long-term follow up
• Not yet aware of disease-modifying therapies; counseled regarding NG/PEG if feeding time exceeds 30 minutes per meal

Summary of History

Karthik is a 5 month old second-born male infant with uneventful birth and early successful breastfeeding, who developed insidious generalized hypotonia at 2 months with rapid progression to proximal symmetrical weakness, bulbar dysfunction, and diaphragmatic-sparing respiratory distress. He shows marked developmental dissociation — gross motor DQ 30% with preserved social, language and cognitive milestones at 100%.

I would like to think of a lower motor neuron disorder localizing to the anterior horn cell, most likely spinal muscular atrophy type 1 (Werdnig-Hoffmann disease), with bulbar weakness and early respiratory muscle involvement, without encephalopathy, upper motor neuron signs, or neuroregression.

General head to toe examination

• Examined supine in mother's lap, awake and interactively smiling
• Vitals
  • Temperature - 36.8°C
  • PR - 124/min, regular, good volume pulses
  • RR - 42/min, tachypneic with diaphragmatic (paradoxical) respiration
  • BP - 86/54 mmHg, right upper limb, supine
  • SpO2 - 97% room air
  • CRT - < 2 seconds
• Anthropometry

• Head to toe Examination
  • Alert, bright-eyed, non-dysmorphic infant in characteristic frog-leg posture with minimal spontaneous lower limb movement
  • Anterior fontanelle flat, soft, 2.0 × 2.0 cm
  • Eyes — normal palpebral fissures, red reflex present bilaterally, no ptosis
  • High-arched palate. Tongue fasciculations at lateral borders at rest
  • Bell-shaped chest — narrow upper thorax, flared lower ribs, intercostal retractions on inspiration
  • No cephalhematoma, subgaleal bleed, or bruising
  • Hyperextensible joints, no contractures, no polydactyly
  • No neurocutaneous markers, jaundice, or pedal edema
  • Testes descended bilaterally in rugated scrotum

Systemic Examination

CNS

• HMF

  • Alert, conscious, interactively responsive — Brazelton State 3/4
  • Bright expressive eyes, coos and smiles appropriately
  • No encephalopathy or irritability

• CN

  • CN II–VI: Fixes and tracks light/objects; pupils 2.5 mm equal reactive; no ptosis or ophthalmoplegia
  • CN V: Facial sensation intact; weak masseter contraction
  • CN VII: Symmetrical facial movements
  • CN VIII: Turns to auditory stimulus
  • CN IX, X: Weak cry, sluggish gag, secretions pooling in pharynx
  • CN XI: Cannot lift head against gravity; severe SCM weakness
  • CN XII: Tongue fasciculations positive at rest; no atrophy

• motor

• Inspection
  • Resting frog-leg posture; upper limbs in jug-handle flexion
  • Spontaneous movements present distally (fingers/toes); absent proximally at hip and shoulder
• bulk — mild generalized symmetrical thinning, equal both sides, masked partially by subcutaneous fat
• tone

• power
  • Upper limbs proximally — grade 1/5 (trace flicker)
  • Upper limbs distally — grade 3/5
  • Lower limbs proximally — grade 0/5
  • Lower limbs distally — grade 2/5
  • Symmetrical; proximal > distal; lower > upper
• Reflexes

• Sensory — withdraws to pinprick distally; intact
• Primitive Reflexes

• Cerebellar — no nystagmus; testing limited by weakness
• No meningeal signs

other systems

• Respiratory system — RR 42/min, bell-shaped chest, paradoxical abdominal breathing, intercostal retractions; symmetrical air entry, scattered fine rhonchi, no crepitations
• Cardiovascular — S1 S2 normal, no murmur, no cardiomegaly (rules out Pompe disease)
• abdominal — soft, non-tender, no hepatosplenomegaly, bowel sounds present

Summary

A 5 month old second order male infant with uneventful perinatal history and retrospectively weak fetal movements, presented with insidious onset generalized hypotonia since 2 months, progressive symmetrical proximal weakness (lower > upper), bulbar dysfunction, and diaphragmatic-sparing respiratory distress. Examination revealed an alert interactive child with frog-leg posture, slipping-through-hands sign, tongue fasciculations, absent deep tendon reflexes with flexor plantars, bell-shaped chest, and developmental dissociation (motor DQ 30%, social/cognitive DQ 100%), without dysmorphism, organomegaly, or upper motor neuron signs.

The probable diagnosis is spinal muscular atrophy type 1 (Werdnig-Hoffmann disease) at anterior horn cell level, non-sitter (GMFCS V equivalent), complicated by bulbar dysfunction, respiratory muscle weakness, and moderate acute malnutrition.

Differential Diagnosis

Investigation Protocol & Diagnostic Workup

flowchart TD
    A["Floppy Infant<br/>Assess Alertness + Reflexes"] --> B{Central or Peripheral?}
    B -->|Alert + Areflexia<br/>+ Fasciculations| C[Peripheral Hypotonia]
    B -->|Lethargic + Hyperreflexia<br/>+ Seizures| D[Central Hypotonia Workup]
    C --> E[Serum CPK]
    E --> F{CPK Level}
    F -->|Normal / Mild ↑| G["SMN1 MLPA / qPCR<br/>+ SMN2 copy number"]
    F -->|Marked ↑| H[Muscle Biopsy / Gene Panel]
    G --> I{SMN1 Result}
    I -->|Homozygous deletion| J[SMA Type 1 Confirmed]
    I -->|Negative| K[EMG/NCV → NGS]
    J --> L["Baseline: CXR, ABG,<br/>Polysomnography"]
    D --> M["MRI Brain, Metabolic Screen,<br/>Karyotype"]

1. Confirmatory Test

• SMN1 gene testing (MLPA / quantitative PCR): Homozygous deletion of exon 7 and/or 8 on chromosome 5q13.2
• SMN2 copy number: Prognostic — Type 1 typically has 2 copies; guides therapy selection

2. Supportive Investigations

• Serum CPK: Normal or mildly elevated (< 2–3×); marked elevation suggests congenital muscular dystrophy
• EMG/NCS: Neurogenic pattern — fibrillations, fasciculations, large polyphasic MUAPs; normal SNAPs. Deferred if SMN1 positive
• Chest X-ray: Bell-shaped thorax, subclinical atelectasis, aspiration changes
• ABG / polysomnography: Nocturnal hypoventilation and hypercapnia monitoring

Management Plan

1. Disease-Modifying Therapies

• Nusinersen (Spinraza): Antisense oligonucleotide enhancing SMN2 splicing — intrathecal loading doses days 0, 14, 28, 63; maintenance every 4 months
• Risdiplam (Evrysdi): Oral SMN2 splicing modifier — $0.2 \text{ mg/kg/day}$ if < 2 months; $0.25 \text{ mg/kg/day}$ if 2 months to 2 years
• Onasemnogene abeparvovec (Zolgensma): Single IV AAV9 gene replacement — $1.1 \times 10^{14}\text{ vector genomes/kg}$

2. Respiratory Support

• BiPAP/NIV: Initiate for nocturnal hypoventilation and paradoxical breathing
• Airway clearance: Cough assist device, chest physiotherapy, oral suctioning
• Prophylaxis: Annual influenza vaccine, palivizumab for RSV season

3. Nutritional & Bulbar Care

• Swallowing assessment: Speech-language therapist referral
• Feeding position: 45° upright; transition to NG tube or PEG if feed duration > 30 min or aspiration risk
• High-calorie formula: Maintain weight velocity without fluid overload

4. Rehabilitation

• Passive ROM exercises: Prevent contractures
• Supported seating: Head and trunk support systems
• Scoliosis surveillance: Serial monitoring as child grows

5. Genetic Counseling

• Inheritance: Autosomal recessive — 25% recurrence risk
• Carrier testing: Both parents
• Prenatal diagnosis: CVS at 10–12 weeks or amniocentesis at 15–18 weeks in future pregnancies
• Parent support groups: SMA foundation referral

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