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§ |