Table 1.
The type of inheritance and genes associated with different forms of skeletal dysplasia
| Group or name of the disorder FGFR3 disorders | Mode of Inheritance | Gene Symbol |
|---|---|---|
| Thanatophoric dysplasia | AD | FGFR3 |
| Achonodroplasia | AD | FGFR3 |
| Hypochondroplasia | AD | FGFR3 |
| SADDNA | AD | FGFR3 |
| Type II collagen disorders | ||
| Achondrogenesis II | AD | COL2A1 |
| Hypochondrogenesis | AD | COL2A1 |
| Spondyloepiphyseal dysplasia congenita (SEDC) | AD | COL2A1 |
| Kniest dysplasia | AD | COL2A1 |
| Type X1 collagen disorders | ||
| Fibrochondrogenesis | AR | COL11A1 |
| Fibrochondrogenesis | AD | COL11A1, COL11A2 |
| Otospondylomegaepiphyseal dysplasia (OSMED) | AR | COL11A2 |
| Sulfation disorders | ||
| Achondrogenesis IB | AR | SLC26A2 |
| Atelosteogenesis II | AR | SLC26A2 |
| Diastrophic dysplasia | AR | SLC26A2 |
| Chondrodysplasia with congenital joint dslocations | AR | CHST3 |
| Perlecan disorders | ||
| Dyssegmental dysplasia | AR | PLC |
| Dyssegmental dysplasia, Silverman-Handmaker type | AR | PLC |
| Dyssegmental dysplasia, Rolland Desbuquois type | AR | PLC |
| Filamin Disorders and similar disorders | ||
| Otopalatodigital syndrome I and II | XLD | FLNA |
| Osteodysplasty, Melnick-Needles | XLD | FLNA |
| Atelosteogenesis types I and III | AD | FLNB |
| Larsen syndrome | AD | FLNB |
| Spondylo-carpal-tarsal dysplasia | AR | FLNB |
| Serpentine fibula-polycystic kidney syndrome | AD | NOTCH2 |
| TRPV4 disorders | ||
| Metatopic dysplasia | AD | TRPV4 |
| Short-rib dysplasias (with and without polydactyly) | ||
| Chondroectodermal dysplasia (Ellis-van Creveld (EVC) | AR | EVC1, EVC2 |
| Short-rib polydactyly syndrome I, II, III and IV including Asphxiating Thoracic Dystrophy | AR | DYNC2H1, IFT80NEKWDR35WDR19WDR34 |
| Thoracolaryngeal dysplasia | AD | unknown |
| Metaphyseal dysplasias | ||
| Cartilage-hair hypoplasia | AR | RMRP |
| Metaphyseal dysplasia, Jansen type | AD | PTHR1 |
| Spondylo-epi-(meta)-physeal dysplasia | ||
| SEMD, short limb abnormal calcification type | AR | DDR2 |
| Severe spondylodysplastic dysplasias | ||
| Achondrogenesis 1A | AR | GMAP210 |
| Schneckenbecken dysplasia | AR | SLC35D1 |
| Opsismodysplasia | AR | INPPL1 |
| Acromesomelic disorders | ||
| Acromesomelic dysplasia, type Maroteaux | AR | NPR2 |
| Mesomelic and rhizo-mesomelic dysplasias | ||
| Langer type (homozygoud dyschondrosteosis | pseudo-AR/XLD | SHOX |
| Omodysplasia | AR | GPC6 |
| Robinow syndrome, recessive | AR | ROR2 |
| Robinow syndrome, dominant | AD | WNT5 |
| Bent bone dysplasias | ||
| Campomelic dysplasia | AD | SOX9 |
| Stuve-Wiedemann dysplasia | AR | LIFR |
| Bent bone dysplasia FGFR2 type | AD | FGFR2 |
| Slender bone dysplasias | ||
| Microcephalic osteodysplastic primordial dwarfism (MOPD1) | AR | RNU4ATAC |
| Microcephalic osteodysplastic primordial dwarfism (MOPD2) | AR | PCNT |
| Osteocraniostenosis | FAM111A | |
| Dysplasias with multiple joint dislocations | ||
| Desbuquois dysplasia | AR | CANT1, XYLT1 |
| Pseudodiatrophic dysplasia | AR | unknown |
| Chondrodysplasia punctata group (CDP) | ||
| CDP, X-linked dominant | XLD | EBP |
| Conradi-Hunermann type (CDPX2) | XLR | ARSE |
| brachytelephalangic type (CDPX1) | XLD | NSDHL |
| CHILD syndrome | XLD | EBP |
| Greenberg dysplasia | AR | LBR |
| Rhizomelic CDP type 1 | AR | PEX7 |
| Rhizomelic CDP type 2 | AR | DHPAT |
| Rhizomelic CDP type 3 | AR | AGPS |
| Neonatal osteosclerotic dysplasias | ||
| Bloomstrand dysplasia | AR | PTHR1 |
| Desmosterolosis | AR | DHCR24 |
| Caffey disease (infantile) | AD | COL1A1 |
| Raine dysplasia | AR | FAM20C |
| Increased bone density group | ||
| Osteopetrosis (severe neonatal or infantile forms) | AR | TCIRG1 |
| Osteopetrosis (severe neonatal or infantile forms) | AR | CLCN7 |
| Dysosteosclerosis | AR | SLC29A3 |
| Lenz-Majewski hyperostostic dysplasia | SP | PTDSS1 |
| Osteogenesis imperfecta and decreased bone density group | ||
| Osteogenesis imperfecta, moderate, severe and perinatal lethal | AD | COL1A1, COL1A2 IFITM5 |
| Osteogenesis imperfecta, moderate, severe and perinatal lethal | AR | CRTAP P3H1 PPBI FKBP10 HSP47 SP7 WNT1 TMEM33B |
| Bruck syndrome | PLOD2 FKBP10 | |
| Osteoporosis-pseudoglioma syndrome | AR | LRP5 |
| Cole-Carpenter dysplasia | SP | unknown |
| Abnormal mineralization group | ||
| Hypophosphatasia, perinatal and infantile forms | AR | ALPL |
Figure 1.
MRI findings of DD patient: Scoliosis (4th grade), osteochondrosis, spondyloarthritis of the spine. Protrusions of disks C3-C4, C4-C5, C5-C6, C6-C7, L5-S1
Figure 2, 3, 4.
The phenotypic traits of DD patient: brachydactylia (short fingers), absence of flexion creases of the fingers, and proximally placed, abducted «hitchhiker thumb».
Table 2.
The identified in DD patient gene variants.
| GENE | VARIANT | ZYGOSITY | VARIANT CLASSIFICATION |
|---|---|---|---|
| SLC26A2 | c.1020_1022del (p.Val341del) | heterozygous | PATHOGENIC |
| SLC26A2 | c.1957T>A (p.Cys653Ser) | heterozygous | PATHOGENIC |
| LTBP2 | c.3913G>C (p.Asp1305His) | heterozygous | Uncertain Significance |
| TTC21B | c.3932G>A (p.Arg1311His) | heterozygous | Uncertain Significance |