Table 1 Clinical manifestations in individuals with variants in collagen XII and VI

Sex

M

F

F

F

M

M

M

M

Molecular diagnosis

4 years

4 years

8 years

10 years

39 years

7 years

18 years

2 years

Early development

Motor delay

Walked at 17 months

Walked at 19 months

Walked at 12 months

Normal

Walked at 27 months

Toe walking, fine motor skills ↘

Walked at 24 months

  Hypotonia

+

Neonatal

Neonatal

-

-

+

-

Neonatal

  Muscle biopsy

Normal

NA

NA

NA

NA

Discrete perimysium fibrosis

Muscle atrophy

NA

  Talipes equinovarus

-

-

Congenital

-

Congenital

-

At 12 months

-

  Contractures

Congenital: fingers, elbows, ankles

-

Congenital torticollis

-

-

Knee, congenital adducted thumbs

Progressive in hands, feet, shoulder

Progressive in hips, knees, elbows

  Joint laxity (BS)

Generalized

Generalized (7/9)

Generalized (9/9)

Generalized (9/9)

Moderate

Distal

-

Generalized (9/9)

  Luxation

-

-

-

-

Patella

-

-

Shoulder

  CB hip dislocation

-

-

+

+

-

+

-

-

  Pes planus

+

+

-

-

-

+

-

+

 Deformities

-

+/− Scoliosis, pectus deformity, tapered fingers

Pectus excavatum

-

-

Hyperlordosis

-

-

  Others

Proximal muscle weakness

Muscle mass ↘

Fatigue, reduced exercise tolerance

Pain in feet, legs

-

Neonatal laryngomalacia, failure to thrive

Limited mobility in hips, knees, (pain in neck, back)

Muscle weakness, muscle strength ↘

  Soft/pale

+

+

+

-

-

+

-

+

  Hyperextensible

-

-

+

-

-

-

-

+

  Easy bruising

-

-

-

-

-

-

-

+

 Wound healing ↘

-

-

+

-

-

-

-

-

  Micrognathia

-

+

+

-

-

+

-

-

  Light blue sclerae

-

+

+

+

-

-

-

-

  High arched palate

-

+

-

+

-

-

-

-

  Eyes

-

-

Myopia

-

-

-

-

Large, bilateral epicanthic folds

 CK

198 U/L (4 years)

258 U/L (<4 years), 170 U/L (6 years)

73 U/L (13 years)

NA

254 U/L (40 years)

NA

146 U/L (22 years), childhood: +/− ↗

NA