Table 1.

Clinical details of P1 and P2.

	Patient 1 (P1)	Patient 2 (P2)
Sex/age (years)	Male/4	Female/3
Tpm3.12 mutation	ΔE224	ΔE218
Presentation	Decreased fetal movements. At birth: stiffness with arthrogryposis multiplex congenital, right clubfoot, bilateral hand fisting, inguinal hernia, bilateral hip dysplasia, and knee contractures.	At birth: pronounced generalized stiffness, limited to absent movement, including the thoracic muscles requiring ventilation, hip dysplasia, umbilical hernia, left inguinal hernia. In infancy: recurrent hypoxic crises.
Dysmorphic features	Relative macrocephaly, short stature, and thin habitus. Prominent forehead, small mouth, short neck, and stiff face.	Retrognathia, micrognathia, and short neck.
Cognition	Normal	Normal
Clinical features	Kyphoscoliosis with lower spinal rigidity. Mild head lag, no slip-through, variable tone distally. Multiple bilateral contractures: shoulders, wrists with ulnar deviation, finger flexors, jaw, hip flexion, knee flexion, and heel cords. Prominent paraspinous muscles. Fine tremor. Reflexes present. Temperature dysregulation.	Pronounced muscle hypertonia. Kyphosis. Limited passive range of motion. Thoracic rigidity. Tracheostomy, ventilator and feeding tube dependent. She has a bladder catheter. Profuse sweating when excited.
Motor function & strength	Stiff gait marked by hip flexion, thoracic kyphosis, and flexion at the knees. Improvement over time. Strong bilateral grasp. No weakness.	Limited to absent movement. Unable to sit or roll.
Respiration	Neonatal transient hypoxemia. Increased respiratory rate and occasional grunting. Frequent respiratory infections. Hypoxemia and obstructive sleep apnea requiring supplemental oxygen.	Recurrent hypoxic crises in infancy. Tracheostomy and ventilator dependency.
EMG	Suggestive of a generalized myopathy with denervating features. No myotonia or myokymia observed.	No evidence of spontaneous activity or myotonia.
NCS	Sensory responses of the right median and sural nerves were normal. Motor NCS of the right median nerve showed normal distal latency, moderate reduction in response amplitude and normal conduction velocity. Motor NCS of the right peroneal nerve showed normal distal latency, severe reduction in response amplitude, and normal conduction velocity.	Not performed.
Other	CK: 205 U/L. Normal: EEG, brain MRI, and Echo. Negative: ACTA1, MYH3, TPM2, HSPG2, TNNT3, TNNI2, FKRP, CRYAB, and microarray.	CK between 200-1,000 U/L. Osteopenia, shortened phalanges, and clinodactyly on X-ray. Normal: brain MRI, EEG and metabolic screening. Negative ACTA1 and CRYAB. Increased echogenicity on muscle ultrasound.