Muenke syndrome is an autosomal dominant disorder characterized by coronal 
suture craniosynostosis, hearing loss, developmental delay, carpal, and 
calcaneal fusions, and behavioral differences. Reduced penetrance and variable 
expressivity contribute to the wide spectrum of clinical findings. Muenke 
syndrome constitutes the most common syndromic form of craniosynostosis, with an 
incidence of 1 in 30,000 births and is defined by the presence of the 
p.Pro250Arg mutation in FGFR3. Participants were recruited from international 
craniofacial surgery and genetic clinics. Affected individuals, parents, and 
their siblings, if available, were enrolled in the study if they had a 
p.Pro250Arg mutation in FGFR3. One hundred and six patients from 71 families 
participated in this study. In 51 informative probands, 33 cases (64.7%) were 
inherited. Eighty-five percent of the participants had craniosynostosis (16 of 
103 did not have craniosynostosis), with 47.5% having bilateral and 28.2% with 
unilateral synostosis. Females and males were similarly affected with bicoronal 
craniosynostosis, 50% versus 44.4% (P = 0.84), respectively. Clefting was rare 
(1.1%). Hearing loss was identified in 70.8%, developmental delay in 66.3%, 
intellectual disability in 35.6%, attention deficit/hyperactivity disorder in 
23.7%, and seizures in 20.2%. In patients with complete skeletal surveys (upper 
and lower extremity x-rays), 75% of individuals were found to have at least a 
single abnormal radiographical finding in addition to skull findings. This is 
the largest study of the natural history of Muenke syndrome, adding valuable 
clinical information to the care of these individuals including behavioral and 
cognitive impairment data, vision changes, and hearing loss.