From: Molecular landscape of congenital vertebral malformations: recent discoveries and future directions
Gene | MIM | Syndrome | Type of vertebral defect | Others defects |
---|---|---|---|---|
ACVR1 | 102576 | Fibrodysplasia ossificans progressiva | C VMs | SD (short thumbs, fifth finger clinodactyly, short broad femoral necks), deafness, mild mental retardation |
AFF4 | 604417 | CHOPS syndrome | C VMs (ND) | Cardiac defects (VSD, patent ductus arteriosus), intellectual disability, chronic lung disease, obesity, brachydactyly, horseshoe kidney, dysmorphic facial features, tracheomalacia, subglottic and tracheal stenosis, cryptorchidism, hearing loss |
ARSL | 300180 | Chondrodysplasia punctata, X-linked recessive | Platyspondyly | Craniofacial anomalies, brachycephaly, foot syndactyly, limbs abnormalities |
COL11A1 | 120280 | Fibrochondrogenesis 1, Marshall syndrome, Stickler syndrome, type II | Platyspondyly | Flat midface with a small nose and anteverted nares, shortening of limb segments |
COL2A1 | 120140 | Kniest dysplasia | Platyspondyly | Coronal clefts, slight shortening of the ribs, dumbbell-shaped femurs |
DDRGK1 | 616177 | Spondyloepimetaphyseal dysplasia, Shohat type | Platyspondyly, hypoplasia of L vertebrae, square vertebrae | SD (long bone changes, short neck, L lordosis, limb shortening), hyperlaxity of joints |
EBP | 300205 | Chondrodysplasia punctata, X-linked dominant | Hemivertebrae | SD (asymmetric rhizomelia, epiphyseal stippling),cataracts |
FN1 | 135600 | Spondylometaphyseal dysplasia, corner fracture type | Asymmetric vertebral pedicles, hypoplasia of Th12, ovoid VBs, irregular vertebrae | SD (thoracolumbar scoliosis, metaphyseal dysplasia, short stature) |
GDF11 | 603936 | Vertebral hypersegmentation and orofacial anomalies | C, Th, L vertebrae hypersegmentation | SD (rib abnormalities, hypermobile joints, winged scapulae), orofacial anomalies, ear anomalies |
GPC3 | 300037 | Simpson-Golabi-Behmel syndrome, type 1 | Th hemivertebrae | Sprengel’s deformity |
GPC4 | 300168 | Keipert syndrome | VMs (ND) | Ribs, sternum, pelvis abnormalities |
HSPG2 | 142461 | Dyssegmental dysplasia, Silverman-Handmaker type | Anisospondyly | Neonatal short-limbed dwarfism |
INPPL1 | 600829 | Opsismodysplasia | Platyspondyly | SD (short hands/feet, short long bones, bony under mineralization, short and square metacarpals and phalanges, L kyphosis, narrow chest, small and cupped pubic bones), Eye defects (hypertelorism, proptosis/shallow orbits) |
JAG1 | 601920 | Alagille syndrome 1 | Butterfly vertebra, Decrease in interpediculate distance in the lumbar spine | Eye defects (posterior embryotoxon and retinal pigmentary changes), heart defects (pulmonic valvular stenosis, peripheral arterial stenosis), nervous system abnormalities, facial dysmorphism (broad forehead, pointed mandible and bulbous tip of the nose and in the fingers, varying degrees of foreshortening) |
KIAA0586 | 610178 | Short-rib thoracic dysplasia 14 with polydactyly | Th6 butterfly vertebra | SD (small chest with short ribs, bilateral hand post-axial polydactyly, short limbs), cleft palate, lower gingiva clefts, vision defects (papillary coloboma and atrophy of the choroid-retinal inferopapillary) |
KIAA1217 | 617367 | N/A | C, Th fusion, hemivertebrae, wedged-shape vertebrae | SD (Sprengel deformity), cardiac defects (ASD, VSD, dextrocardia, myocarditis), central nervous system abnormalities (hydrocephalus, macrocephaly, tethered cord, cerebellar tonsillar prolapse into spinal canal, basilar invagination) |
LBR | 600024 | Rhizomelic skeletal dysplasia with Pelger-Huet anomaly | Platyspondyly and ovoid VBs | SD (short limbs, shortened ribs) |
NADSYN1 | 608285 | Vertebral, cardiac, renal, and limb defects syndrome 3 | Butterfly vertebra, hemivertebra, L, Th wedge-shaped vertebra | Rib abnormalities, heart defects (mitral insufficiency, bicuspid aortic valve, mitral valve prolapse), renal aplasia, diastematomyelia, tethered cords, hepatic polycysts |
NOTCH2 | 600275 | Hajdu-Cheney Syndrome | Increased anterior height of the L VBs with reduced intervertebral distances | SD (wormian bones, serpentine fibulae, bathrocephaly, irregular tooth positioning, abnormal curvature of the C spine), polycystic kidneys, ventricular septal defect, facial dysmorphism (a thin upper lip, downturned mouth, wide nasal tip, long and flat philtrum, dysplastic and posteriorly rotated ears, and short neck), hearing loss, hypothyroidism |
NSDHL | 300275 | CHILD syndrome | VMs (ND) | Absence of several facial muscles, shortening of right leg, VSD |
PDE4D | 600129 | Acrodysostosis 2, with or without hormone resistance | L stenosis (absence of normal interpedicular widening in the lumbar vertebrae) | SD (short stature, small hands, midface hypoplasia), developmental disability |
POGZ | 614787 | White-Sutton syndrome | Hypoplasia of the C VBs | Short stature, microcephaly, non-ocular visual impairment, failure to thrive, diaphragmatic hernia, a duplicated renal collecting system |
SLC26A2 | 606718 | Achondrogenesis Ib Atelosteogenesis, type II De la Chapelle dysplasia | Deficient ossification in the L vertebrae, C kyphosis, scoliosis, and lumbar hyperlordosis with horizontal sacrum, flattened vertebrae with coronal clefts | SD (shortened limbs, small chest, clubfoot), respiratory insufficiency |
SLC29A3 | 602782 | H Syndrome | “Sandwich” vertebrae and platyspondyly | Anemia, bilateral femoral fractures |
SLC35D1 | 610804 | Schneckenbecken dysplasia | Retardation of the VBs ossification | SD (handle bar clavicle, bell shaped thorax, ossification of the posterior arch, interpediculate distance narrowing, sacral, pubic, tarsal ossification) |
SOX9 | 608160 | Campomelic dysplasia | Hypoplastic pedicles of Th vertebrae | SD (very small scapulas, dislocated hips, talipes equinovarus deformities, small thoracic cage), respiratory distress, renal and heart malformations |
SUMF1 | 607939 | Multiple sulfatase deficiency | VMs (ND) | Bilateral cataracts, retinal atrophy, ichthyosis, hepatosplenomegaly, psychomotor retardation |
TNFRSF11A | 602080 | Paget disease of bone 2, early-onset | “Sandwich” vertebra | Osteoporosis |
TRPV4 | 605427 | Spondylometaphyseal dysplasia | Platyspondyly, dense wafer vertebrae | SD (congenital scoliosis, rib abnormalities, flared iliac wings, halberd pelvis, irregular proximal femoral growth plate, brachydactyly, carpal ossification delay), contracture |