TABLE 2.

Clinical features and ultrastructural and biochemical abnormalities observed in spEDS-B3GALT6 and SEMD-JL1 individuals compared to the b3galt6^–/– zebrafish model.

		Human		Zebrafish
		spEDS-B3GALT6	SEMD-JL1	b3galt6–/– mutant
General morphology
	Short stature	22/30	11/14	Reduced body length
	Craniofacial dysmorphisms (e.g., midfacial hypoplasia, micrognatia)	25/30	12/14	Deformed, small and round head with shorter parietal/occipital region and underdeveloped olfactory region
	Dental abnormalities	14/30	n.a.	Smaller teeth
Musculoskeletal involvement
	Bowing of limbs, metaphyseal widening or vertebral body changes	20/30	14/14	Deformities of the fin skeleton
	Bone fragility with spontaneous fractures	19/30	0/3	Extra intramembranous bone, lower degree of collagen type I fibril organization and higher TMD after correction for smaller size
	Joint contractures (especially hands)	23/30	5/14	Pectoral fins point upwards
	Joint hypermobility	26/30	6/14	n.a.
	Kyphoscoliosis	23/30	13/14	Kyphosis and scoliosis
	Muscle hypotonia	18/30	1/14	Reduced critical swimming speed and endurance
Skin features
	Skin hyperextensibility	19/30	2/14	n.a.
Biochemical findings
	Reduced GAG synthesis	9/9	4/4 (3/4; <HS but >CS/DS)	Reduced GAG production
Ultrastructural findings
	Loosely packed collagen fibrils	1/1	n.a.	Disturbed collagen fibril organization in bone and loosely packed collagen fibrils in the dermis

n.a., not available; GAG, glycosaminoglycan. The columns “spEDS-B3GALT6” and “SEMD-JL1” summarize the most important clinical features of all hitherto reported patients for whom this data was available (Van Damme et al., 2018; Caraffi et al., 2019).