Table 1 Clinical manifestations and COL2A1 variants of five Japanese children with spondyloepiphyseal dysplasia congenita.

Individual patient

1

2

3

4

5

Gene mutation (COL2A1:NM_001844.5)

exon23:c.1421G>T:p.G474V (novel)

exon25:c.1628G>A:p.G543E (novel)

exon26:c.1699G>A:p.G567S (novel)

exon27:c.1780G>A:p.G594R (ClinVar: pathogenic)

exon50:c.3508G>C:p.G1170R (ClinVar: likely pathogenic)

Inheritance

De novo

Maternal inheritance

De novo

Paternal inheritance

De novo

Age at genetic testing

11 months

7 years 3 months

2 years 4 months

7 years 11 months

2 years 5 months

Sex

Female

Male

Female

Female

Male

Gestation

39 weeks 2 days

35 weeks 0 days

39 weeks 3 days

39 weeks 0 days

39 weeks 4 days

Birth length (cm)

45 (−2.1 SD)

36 (−3.2 SD)

45 (−2.1 SD)

46.2 (−1.3 SD)

46.0 (−1.2 SD)

Birth weight (g)

2650 (−1.1 SD)

2074 (−0.82 SD)

3176 (−0.44 SD)

2768 (−0.30 SD)

2642 (−1.2 SD)

Head circumference (cm)

32.5 (−0.56 SD)

N/A

32.0 (−0.97 SD)

33 (−0.16 SD)

33.9 (−0.46 SD)

Age when measured

N/A

7 years 2 months

4 years 1 month

8 years 11 months

2 years 4 months

Height (cm)

N/A

71.5 (−9.6 SD)

86.5 (−3.6 SD)

121.0 (−1.5 SD)

68.2 (−6.3 SD)

Weight (kg)

N/A

11.1 (−3.0 SD)

13.5 (−0.9 SD)

22.6 (−1.0 SD)

8.45 (−3.0 SD)

Head circumference (cm)

N/A

N/A

44.2 (−0.3 SD)

51.0 (+0.5 SD)

49 (+0.1 SD)

Orthopedic findings

N/A

Bilateral femoral bone exodeviation and no cervical spinal stenosis at 3 years 6 months, no visaible femoral bone epiphysis at 9 years

Cervical vertebra plana, odontoid hypoplasia

Mild bilateral pes planovalgus at 1 year 9 months, Perthes-like deformity at 3 years

Coxa vara, flat feet, cervical cord compression due to C1-C2 instability

Ophthalmological findings

Refer

Amblyopia (eye glasses)

Hyperopia, astigmatism

No abonormality

Refer

Audiological findings

N/A

Sensorineuroal hearing loss (hearing aids)

Normal

No abonormality

N/A

Oropharyngeal findings

N/A

Physical examination findings

Short stature

Short stature

Short extremities, short neck

Short stature

Short stature, relative macrocephaly

Developmental milestones

N/A

Head control 2 years 6 months, roll over 2 years 9 months, crawl 3 years, unable to stand with support at 9 years

Head control 4 months, roll over 5 months, crawl 6 months, stand with support 8 months, walk with support 11 months

Head control 3 months, sit unsupported 9 months, stand with support 10 months, stand unsupported 12 months, walk unsupported 15 months

Walk unsupported 2 years 4 months, speech normal

Other findings