Common skeletal features in rare diseases

Figures & data

Figure 1. Skeletal preparations of wild-type and Fuz^−/− embryos at E18.5. Alizarin red staining marks the bone. Alcian blue staining marks the cartilage. (A and B) Dorsal views of the skull. (A) Control. (B) Mutant mice display synostosis of the coronal suture (yellow arrowhead) as well as an open anterior fontanelle (yellow asterix). (C and D) Dorsal view of the axial skeleton. (C) Control. (D) In mutant animals, the cervical vertebra (cv, bracket) are fused. Ossification of the centrum in thoracic vertebra is lost or aberrant (yellow arrow). (E and F) Frontal views of the sternum. (E) Control. (F) In mutants, the sternum is shorter, hyperossified and cleft/bifid (black arrow).

Table 1. Skeletal phenotypes observed in ciliopathies and FGF syndromes. Included are selected human disorders and animal models. Unfortunately, due to space constraints, we regret that we are unable to cite all relevant papers.

	Affected structure
	Skull/Face	Palate	Limb Hand	Vertebra	Rib/Thorax	Sternum	Refs.
	Ciliopathies
Human
Meckel	encephalocele	C	PD	?	-	-	20
Bardet-Biedl	Shape change	HA	PD, SD	scoliosis	-	-	37
Joubert	-	C?	-	Cervical fusion	-	-	28
OFD1	Shape change	HA	PD	-	-	-	20
Jeune	-	-	PD	Cervical stenosis	irregular	bulge	9, 38
Sensenbrenner	SS	HA	SL, PD	-	Short ribs	-	13, 39–41
Ellis-Van Creveld	-	-	SL, PD	-	Short ribs	-	42
Mouse Models
Meckel: MKS1^hlb614/MKS1^krc	-	C	-	-	-	bifid, fused	35, 43
Ellis-van Creveld: EVC	-	-	SL	Fusions	Short ribs	-	44, 45
Orofacial Digital: OFD1	-	C	SL, PD	-	-	bifid, fused	46, 47
Sensenbrenner: WDR35	-	-	-	-	Short ribs	-	48
Ciliopathy: Fuz	CS	HA	SL, PD	Cervical fusion	Short ribs	Fused, bifid	14, 16–18
	Craniosynostosis
Human
Apert	CS	HA	SD	Cervical fusion	-	-	19, 49
Crouzon	CS	HA	SL, SD	Cervical fusion	-	-	21, 50
Pfeiffer	CS	HA	SD	Cervical fusion	-	-	22, 23
Mouse Models
Crouzon/Pfeiffer: Fgfr2c^C342Y	CS	C	-	-	-	Fused	51, 52
Pfeiffer: Tg(Fgfr1^P252R)	CS	-	PD	Homeotic transformation	-	Fusions	27
Apert: Fgfr2^IIIc/∆	CS	-	-	-	-	Fused	29, 53
Apert: Fgfr2^S252W	CS	C	-	-	-	Fusions	30
	Chondrodysplasia
Human
Chondrodysplasia punctata 2	variable	-	SL	Scoliosis Fusions	calcified	calcified	20
Hypochondroplasia	variable	-	SL	stenosis	-	-	53
Thanatophoric dysplasia	-	-	SL	flattened	Short ribs	-	54
Achondroplasia	Small base	-	SL	stenosis	Small chest	-	55
Mouse Models
Achondroplasia: Fgfr3^G374R	-	-	SL	Cervical fusion	-	-	56
Thanatophoric Dysplasia: FGFR3^369	-	-	SL	-	Short ribs	-	57

Abbreviations: SS, sagittal synostosis; CS, coronal synostosis; C, cleft palate; HA, high arched palate; PD, polydactyly; SD, syndactyly; SL, short limbs

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