Mutations in the gene that encodes Fibroblast Growth Factor Receptor 3 (FGFR3) 
are associated with Achondroplasia (MIM 100800), Hypochondroplasia (MIM 146000), 
Muenke Syndrome (MIM 602849), Thanatophoric Dysplasia (MIM 187600, MIM 187601) 
and Lacrimo-Auriculo-Dento-Digital Syndrome (MIM 149730).Here we report a 
clinical and molecular study in a large cohort of 125 Portuguese patients with 
these skeletal disorders. The identification of the P250R mutation allowed the 
confirmation of the Muenke Syndrome in 9 out of the 52 cases referred. Two known 
mutations were found in the Thanatophoric Dysplasia referred cases. No mutations 
were identified in the LADD syndrome patient. In Achondroplasia and 
Hypochondroplasia, genetic heterogeneity was present amongst the 70 clinically 
diagnosed patients with 5 different mutations identified. As in other studies, 
complex phenotypic heterogeneity amongst patients carrying the same gene defect 
was observed. In several cases, the new amino acids encoded, as a consequence of 
mutations, were related to the severity of patients' phenotype. The presence of 
10 misdiagnosed cases emphasizes the importance of performing mutation analysis 
of the hotspot regions responsible for both dysplasias (Ach and Hch). For 
patients with an unquestionable clinical diagnosis, lacking the most common 
mutations, a complete screening of FGFR3 is necessary.