Fontaine-Farriaux syndrome: a recognizable craniosynostosis syndrome with nail, skeletal, abdominal, and central nervous system anomalies.

Craniosynostosis is an etiologically heterogeneous malformation, which may present as an isolated finding or in association with other anomalies. The concurrence of craniosynostosis together with specific central nervous system, abdominal, genital, and limb malformations defines the Fontaine-Farriaux syndrome, described so far in only two patients. We report on a stillborn who mainly presented severe intrauterine growth retardation, bilateral coronal synostosis, generalized nail hypo/aplasia more evident on the posterior side, tapered digits, mild cutaneous syndactyly, abdominal muscle hypoplasia, micropenis and bilateral cryptorchidism. Skeletal radiographs revealed universal platyspondyly and necropsy findings comprised intestinal malrotation, abnormal cortical gyral formation, periventricular heterotopia, and cerebellar hypoplasia. Comparison between the present and the two previously described patients demonstrates that our case shows a combination of features strikingly resembling the original description. Conversely, the second reported patient shows a very atypical phenotype and is, most probably, affected by a distinct clinical entity. The triad of craniosynostosis, anonychia, and abdominal muscle hypo/aplasia emerges as the most consistent core phenotype, although skeletal and brain anomalies are relevant ancillary findings. An in-depth differential diagnosis with other partially overlapping conditions is carried out.

Identification of a novel duplication in the APC gene using multiple ligation probe amplification in a patient with familial adenomatous polyposis.

Germline mutations in the adenomatous polyposis coli (APC) gene cause familial adenomatous polyposis (FAP), an autosomal dominant disease characterized by hundreds to thousands of adenomatous polyps in the colon and rectum, with progression to colorectal cancer. The majority of APC mutations are nucleotide substitutions and frameshift mutations that result in truncated proteins. Recently, large genomic alterations of the APC gene have been reported in FAP. DNA from 15 FAP patients, in whom no APC germline mutations were detected with denaturing high performance liquid chromatography, was analyzed with multiplex ligation-dependent probe amplification (MLPA) to evaluate gross genomic alterations in the APC gene. In one case, MLPA identified a novel duplication of exons 2-6 in one copy of the APC gene. Reverse transcriptase-polymerase chain reaction revealed that the mutant allele contained an in-frame multiexon duplication including 18 nucleotides located in exon 2, upstream of the ATG initiation codon. The presence of a premature stop codon in the duplicated sequence leads to the synthesis of a truncated APC polypeptide. These findings highlight the utility of evaluating infrequent APC mutation events in FAP patients using MLPA.