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Table 2 Summary of patients with categorisation, features, and pre- and post-testing diagnosis

From: Diagnostic yield of rare skeletal dysplasia conditions in the radiogenomics era

Patient Sex Age Category Clinical presentation Variants Inheritance Studies Revised diagnosis
1 M 11y K–K Spondyloepiphyseal dysplasia tarda
X- Linked
Hemizygous deletion of TRAPPC2 exon 6 Maternally inherited Spondyloepiphyseal dysplasia tarda (X-Linked)†
2 F 10y K–K Spondyloepiphyseal dysplasia congenita Heterozygous SOX9 c.508C > T, p.(Pro170Ser) variant detected De-novo variant not present in parents Surviving campomelic dysplasia (CD)†
3 F 5 m K–K Syndromal proportional extreme short stature, Chiari malformation type I, growth hormone deficiency, hydrocephalus. Suspected Laron syndrome No pathogenic variants were detected Not applicable SD of unknown aetiology‡
4 F 0-1y K–U Mild fibrochondrogenesis type 2. Post radiological review, changed to severe otospondylomegaepiphyseal dysplasia Heterozygous COL11A2
c.2542C > T p.(Gln848Ter) variant detected (mat)
Heterozygous COL11A2 c.3151-2delA variant detected (pat))
AR—one variant inherited from each parent—trans Severe otospondylomegaepiphyseal dysplasia†
5 F 6y K–U Multiple epiphyseal dysplasia with non-specific myopathy, or metaphyseal dysplasia Heterozygous MATN3 c.400G > A p.(Glu134Lys) Variant not present in mother. Father not tested Multiple epiphyseal dysplasia†
6 F 8y K–U Intrauterine growth restriction (IUGR), failure to thrive, developmental delay, microcephaly, dysmorphisms, short stature. Type of microcephalic osteodysplastic primordial dwarfism Heterozygous PCNT c.5812C > T p.(Gln1928Ter) variant detected
Heterozygous PCNT c.9273 + 1G > C variant detected
AR—one variant inherited from each parent—trans Microcephalic osteodysplastic primordial dwarfism type II†
7 M 3y K–U Metaphyseal chondromatosis with D2-hydroxyglutaric aciduria Heterozygous IDH1 c.395G > A p.(Arg132His) variant detected De novo—variant not present in parents Metaphyseal chondromatosis with D2-hydroxyglutaric aciduria†
8 F 2y K–U Chondrodysplasia punctata. Query genetic or teratogen No pathogenic variants were detected Not applicable Possible acquired aetiology§
9 F 11y K–U AR osteopetrosis (infantile onset) Heterozygous
CLCN7 c.1468delC p.(Leu490fs) variant detected (pat)
Heterozygous
CLCN7 c.1853C > A p.(Ala618Asp) variant detected (mat), VUS
AR—one variant inherited from each parent—trans AR osteopetrosis type 4 (infantile onset) †
10 M 12y K–U Acromesomelic dysplasia, Maroteaux type, or spondylarperipheral No pathogenic variants were detected Not applicable SD of unknown aetiology‡
11 F 3y K–U Odontochondrodysplasia No pathogenic variants were detected Not applicable Odontochondrodysplasia¶
12 M 1y U–U Disproportionate short stature, conductive hearing loss, percutaneous endoscopic gastrostomy fed, dysmorphisms No pathogenic variants were detected Not applicable SD of unknown aetiology‡
13 F 2y U–U SD; congenital heart disease, hemimegaloencephaly, bilateral iris colobomata, hearing loss Heterozygous EXT2 c.237G > A p.(Trp79Ter) variant detected (mat)
Heterozygous EXT2 c.1404 + 2 T > C variant detected (pat)
AR—one variant inherited from each parent—trans Autosomal recessive exostosin glycosyltransferase 2 syndrome^
14 M 7y U–U Query EDS (classic type/collagenopathy), or Mandibular acrodysplasia type A No pathogenic variants were detected Not applicable SD of unknown aetiology‡
15 F 6y U–U Unknown SD, rule out bone marrow transplant-related short stature No pathogenic variants were detected Not applicable Bone marrow transplant-related short stature§
  1. Confirmed molecular diagnosis
  2. Unknown diagnosis
  3. §Possible acquired diagnosis
  4. Confirmed clinical diagnosis but nil molecular findings
  5. ^Possible molecular diagnosis
  6. K–K known condition–known condition; K–U known condition–unknown condition; U–U unknown condition–unknown condition; SD skeletal dysplasia; AR autosomal recessive; TRAPPC2 tracking protein particle complex, subunit 2; SOX6 sex determining region Y-box 6); COL11A2 collagen type XI alpha-2 chain; MATN3 matrilin-3; PCNT pericentrin; IDH1 isocitrate dehydrogenase 1; CLCN7 chloride voltage-gated channel 7; VUS variant of unknown significance; EXT2 exostosin glycosyltransferase 2; EDS Ehlers–Danlos syndrome