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A rare skeletal dysplasia characterized by short stature, prominent abnormalities in hands and feet, and a characteristic facial appearance (described as happy'').
ORPHA:2623Classification level: Disorder
Fewer than 30 cases have been reported to date.
The characteristic facial appearance (''happy'' face) consists in a shortened nose, full cheeks, hypertelorism, long flat philtrum, and a thin upper lip. Additional clinical features include progressive cardiac valvular thickening often leading to an early death, contractions of the gastrocnemius muscle and Achilles tendon leading to tip toe walking, tracheal stenosis, bronchopulmonary insufficiency, and liver enlargement. Radiological manifestations include delayed bone age, cone-shaped epiphyses, shortened long tubular bones and ovoid vertebral bodies.
Mutations have been found in the ADAMTSL2 and FBN1 genes which appear to induce microfibrillar network disorganization and enhanced TGF-beta signaling. FBN1 encodes fibrillin-1 and ADAMTSL2 (Disintegrin And Metalloproteinase with Thrombospondin repeats- like 2) encodes a glycoprotein of unknown function.
Transmission is autosomal recessive in the cases with ADAMTSL2 gene mutations and autosomal dominant in the cases with FBN1 mutations.
A summary on this disease is available in Deutsch (2012) Español (2012) Français (2012) Italiano (2012) Nederlands (2012) Português (2012) Polski (2012, pdf)
- Clinical practice guidelines
- Français (2021) - PNDS
Disease review articles
- Clinical genetics review
- English (2018) - GeneReviews
: produced/endorsed by FSMR(s)