Saethre-Chotzen syndrome is an autosomal dominant disease characterized by 
craniosynostosis, ptosis, and limb and external ear abnormalities. Variable 
expressivity is a well-known phenomenon in this disorder. A large Indian family 
has been recently identified as carrying a nonsense TWIST mutation (Q28 X) in 17 
members, of whom 16 were examined in detail. Only 4 (25%) of the patients showed 
patent craniostenosis, namely, oxycephaly. The penetrance of craniosynostosis in 
this family is lower than previously reported in the literature. Fifteen 
patients (93%) had moderate to severe ptosis. Minor limb and external ear 
abnormalities were present in most patients. Eyelid features were the hallmark 
of the disease for 12 members of the family, suggesting that mutations in TWIST 
may lead to a phenotype with mainly palpebral features and no craniostenosis. 
The clinical analysis of this large family clearly illustrates the significant 
variable expressivity, probably related to haploinsufficiency because of the 
TWIST mutation. This phenotypic variability remains unclear but could be the 
result of modifier genes and/or genetic background effect, as noticed previously 
in the transgenic twist-null heterozygous mice.