Table 1.

Clinical features of the COLVI-RD patients and their mosaic parents

Patient/ sex/age (yrs.)	Mutation	Presentation	Motor Development	Current motor function & strength (MRC grades)	Contractures & skin findings	FVC
F1P/F/13	Heterozygous COL6A2 Exon 7 c.900+1G>A	Hypotonia and head lag at birth.	Gowers’ sign at age 2 yrs. Difficulties with stairs at age 8 yrs., used a scooter at age 9 yrs. Loss of independent ambulation following scoliosis surgery at age 10 yrs.	Unable to transition from supine to sitting. Weakness proximal > distal. Hip flexion 2/5; neck flexion and extension 2/5; remaining proximal muscles 3–4/5.	Distal finger hyperlaxity with coexisting long finger flexor contractures. Contractures of neck flexion, shoulder rotators, elbow flexors L>R, wrist extension, hips, knees, toes. Moderate to severe scapular winging. Keratosis pilaris.	Not done
F1M/M/45	Heterozygous COL6A2 Exon 7 c.900+1G>A	Toe walking at age 2 yrs.	Difficulties with stairs at age 4 yrs. Run with awaked gait and heel cord contractures at age 10 yrs. Increased falls in 20s. Unable to rise from floor at age 38 yrs.	Trendelenburg gait. Minimal acceleration but unable to clear ground, with excessive arm pumping. Weakness proximal > distal. Trunk flexion 2/5; hip flexion 3+/5; neck extension 5/5; remaining distal proximal muscles 4/5.	Distal finger hyperlaxity with coexisting long finger flexor contractures. Contractures of shoulders external rotation, elbows, wrist extension and flexion. Mild scapular wining, rigid spine. Cigarette paper skin, hyperkeratosis pilaris.	Not done
F2P/M/24	Heterozygous COL6A1 Exon 10 c.859G>A p.Gly287Arg	Congenital elbow contractures, hyperlaxity of the fingers.	Started using a walker at age 10 yrs., a scooter at age 11 yrs. Loss of independent ambulation since early teens.	Few short and narrow based steps with assistance. Strength 4-5-/5 range. Hip flexion and extension 3-/5.	Distal finger hyperlaxity, contractures of elbows, knees and ankles. Mild scoliosis, mild keratosis pilaris.	31%
F2M/M/60	Heterozygous COL6A1 Exon 10 c.859G>A p.Gly287Arg	Toe walker, not very athletic, slow runner.	Difficulties with stairs in late 50’s possibly related to back pain from L4-5 herniation	Mild Trendelenburg gait, mild action tremor. Hip flexion 4. Otherwise 5/5 strength.	Bilateral long finger flexor contractures, elbow contractures, slight pectoralis contractures. Mild scoliosis.	71%
F3P/M/16	Heterozygous COL6A1 Exon 11 c.930+2T>A	Delayed motor development noted at 18 months.	Never able to bike. Frequent falls in childhood. Able to walk 15 minutes at age 9 yrs.	Unable to jump. Difficulties rising from chair. Increased fatigue. Proximal muscle weakness in hip flexion 3/5. Truncal weakness. Ascends and descends stairs with two hands on banister.	Distal finger hyperlaxity with coexisting and long finger flexor contractures. Limited shoulder abduction. Rigid spine, keratosis pilaris, keloid scarring.	83%
F3M/M/56	Heterozygous COL6A1 Exon 11 c.930+2T>A	Never very athletic. Unable to run and do push- ups.	Recurrent pulmonary infections in teens.	Mild facial and proximal weakness: biceps, triceps, hip flexors & hip extensors 4/5. Fatigue in arms while swimming.	Mild elbow contractures. Scoliosis, lumbar lordosis, hypertrophic scarring.	Not done
F4P/M/43	Heterozygous COL6A3 Exon 17 c.6238G>T p.Gly2080Cys	Congenital arthrogryposis and bilateral hip dislocation	Achieved walking at 2 yrs. Loss of independent ambulation age 40 yrs. Nocturnal non- invasive ventilation since age 32 yrs.	Severe proximal muscle weakness: deltoids 3/5; biceps and triceps 3+/5; hip flexion 2/5; knee extension 3/5; knee flexion 3/5; dorsiflexion & plantar flexion 3+/5; distal muscles 3/5.	Distal finger hyperlaxity with long finger contractures. Contractures of the elbows, shoulder, jaw, hips, knees and Achilles tendons. Mild lumbar lordosis, rigid spine. Limited shoulder abduction.	30%
F4M/F/75	Heterozygous COL6A3 Exon 17 c.6238G>T p.Gly2080Cys	Never very athletic.		Normal gait. No muscle weakness.	Mild long finger flexor contractures.	Not done
F5M/M/10	Heterozygous COL6A2 Exon 10 c.955-2A>G	Frequent falls noted at age 14 months. Frequent respiratory infections as toddler.	Gowers’ at age 14 months. Tendency to W sit at age 23 months. Able to fast walk but not run.	At age 7 yrs. uses stroller for long distances, rides a bicycle on flat surfaces, independently ambulant, ascends and descends stairs with one hand on banister. Toe walking with waddling-type gait. Neck flexion & trunk flexion 2+/5; elbow flexion & extension 4-5/5 & knee extension 5/5.	Distal finger and toe hyperlaxity. Contractures of the elbows and Achilles tendons. Mild scoliosis.	70% at age 7 yrs.

M= male; F= Female; Yrs = years; CK = Serum Creatine Kinase; FVC=Forced Vital Capacity