OBJECTIVES:To characterize the natural history of 39 achondroplastic patients diagnosed by clinical, radiological and molecular assessments.METHODS:Observational and retrospective study of 39 patients who were attended at a public tertiary level hospital between 1995 and 2016.RESULTS:Diagnosis was made prenatally in 11 patients, at birth in 9 patients and within the first year of life in 13 patients. The most prevalent clinical findings were short stature, high forehead, trident hands, genu varum and macrocephaly. The most prevalent radiographic findings were rhizomelic shortening of the long bones and narrowing of the interpediculate distance of the caudal spine. There was motor developmental delay in 18 patients and speech delay in 16 patients. The most common clinical intercurrences were middle ear dysfunction, sleep apnea, limb pain and obesity from 2 to 9 years of age. One patient was large for the gestational age but did not develop obesity. One patient developed hydrocephalus at 10 years old. The current age of the patients varies from 15 months to 36 years. The molecular study performed by Sanger sequencing of the common heterozygous mutation 1138G>A in FGFR3 was positive in all patients. Four cases were inherited, and 35 were sporadic (paternal age from 19 to 66 years).CONCLUSIONS:The diagnoses were made early based on clinical and radiographic findings. All cases were confirmed molecularly. Despite presenting a benign course, it is necessary to establish a systematic protocol for the surveillance of these patients due to the common clinical intercurrences.

Stüve-Wiedemann syndrome (SWS, OMIM 601559) is a rare autosomal recessive bent-bone dysplasia, caused by loss-of-function mutations in the leukemia inhibitory factor receptor (LIFR) gene, which usually leads to early death. Only few patients with long-term survival have been described in the literature. We report on a 5-year-old boy from a consanguineous marriage with molecular analysis for the LIFR gene. Sanger and next-generation sequencing (NGS) of LIFR were performed. Copy number variation analysis with NGS showed a novel mutation as the cause for the syndrome: an intragenic homozygous deletion in LIFR, involving exons 15-20. Bridging PCR was carried out to confirm the intragenic deletion. This is the first description of a large deletion in LIFR, broadening the spectrum of mutations in SWS. Besides the reported allelic heterogeneity, further studies such as exome sequencing are required to identify a novel gene in order to confirm the locus heterogeneity in SWS.