Definition: Autosomal dominant osteochondrodysplasia associating short limbs, narrow thorax and normal trunk length.
Thanatophoric dysplasia type 1 (TD1) and SADDAN dysplasia are caused by mutation in the gene encoding the fibroblast growth factor receptor-3 (FGFR3; MIM.134934). Thanatophoric dysplasia type 2 (TD2; MIM.187601) and achondroplasia (ACH; MIM.100800) are allelic disorders.
Types
thanatophoric dysplasia type 1
thanatophoric dysplasia type 2
Synopsis
systemic anomalies
- lethal disproportinate dwarfism
- micromelic dwarfism
- severe growth deficiency in survivors
- polyhydramnios
- death in majority of infants soon after birth
craniofacial anomalies
- macrocephaly (large head)
- prominent forehead (frontal bossing)
- secondary skull deformity due to premature closure of cranial sutures (craniostenosis and craniosynostosis)
- relatively large calvaria
- protruding eyes
- small facies (small facial bones)
- depressed nasal bridge
- cloverleaf skull deformity (more frequent in type 2 TD than type 1 TD)
skeletal anomalies
- relatively normal trunk length
- narrow thorax due to short ribs (respiratory insufficiency) with protuberant abdomen
- wide-cupped costochondral junctions
- small abnormally formed scapulae
- short ribs
- small foramen magnum
- cloverleaf skull rarely
- severe platyspondyly
- distinct flattening of the ossification centers of the vertebral bodies (lee severe in type 2 TD than type 1 TD)
- H-shaped appearance of vertebrae
- notch-like ossification defects of the central portion of the upper and lower plates
- short iliac bones
- small iliac bones
- small sacroiliac notches
- short and broad iliac bones
- short and broad ischial bones
- very short limbs (micromelia)
- short and broad long tubular bones
- bowed in type 1 TD (long bone bowing with femorla bowing)
- straigth in type 2 TD
- marked shortness and bowing of long bones
- ’french telephone receiver femurs’
- flared and irregular metaphyses
- short metacarpal bones
- short metatarsal bones
- short phalanges
- bullet-shaped phalanges
cerebral anomalies
- temporal lobe heterotopia
- neuronal heterotopia
- megalencephaly
- cerebral gyral disorganization
- hippocampal malformation
- nuclear dysplasia
- abnormal axonal bundles
- cerebellar hypoplasia
- hydrocephalus
- profound mental retardation and hypotonia in survivors
- polymicrogyria
Variants
thanatophoric dysplasia type 1 (TD1) (MIM.187600)
thanatophoric dysplasia type 2 (TD2) (thanatophoric dysplasia with cloverleaf skull) (MIM.187601)
Associations
bilateral non-obstructive renal dysplasia (BNORD) (17375526)
Differential diagnosis
achondroplasia
PLSDs (platyspondylic lethal short-limbed dysplasias)
- Torrance type PLSD (MIM.151210) (no FGFR3 mutations described)
- San Diego type PLSD (MIM.270230) (FGFR3 mutations)
- Glasgow type PLSD (MIM.273680)
SADDAN syndrome (severe achondroplasia with developmental delay and acanthosis nigricans) (FGFR3 mutations)
Etiology
Locus 4p16.3: germline mutations in the FGFR3 gene
- new cystein in extramembranous segment of the FGFR3
- Lys650GLu in type 2 TD
Case records