A novel insertion in theFGFR2gene in a patient with Crouzon phenotype and sacrococcygeal tail

Abstract

Molecular analysis of the FGFR2 gene in this patient revealed a 12-bp insertion (GAGGAGACCTAG) at nucleotide 824. This is an in-frame mutation that adds four amino acid residues to the immunoglobulin IIIa (IgIIIa) domain of the putative protein. This is the first report of an in-frame insertion in exon 8 of FGFR2 in a child with Crouzon's syndrome, tracheal anomalies, and a tail.

Further evidence of association between mutations in FGFR2 and syndromic craniosynostosis with sacrococcygeal eversion

“…Mouse Fgfr2(IIIb) À/À embryos fail to form the tracheal bifurcation and show defects in lung development (De Moerlooze et al, 2000). In addition, abnormal trachea development or alterations are not rare among FGFR2 mutated patients (Cohen and Maclean, 2000;Scheid et al, 2002;Gonzales et al, 2005;Lapunzina et al, 2005). These, together with the data of the present report, further strengthen the role of FGF/ FGFR signaling in formation of the tracheal system in humans.…”

“…To date, only 6 patients, all with FGFR2 mutations, seem to have been described with syndromic craniosynostosis and cockerel defects: the patient reported here with PS type 3 and pTrp290Cys; a patient with Crouzon's disease with a 12-bp insertion at nucleotide 824 (exon 8) (Lapunzina et al, 2005); 2 PS type 2 patients with mutation Ser351Cys (exon 10) (Gonzales et al, 2005); and 2 other PS type 2 patients with mutation Tyr340Cys (exon 10) (Lajeunie et al, 2006). The different mutations of FGFR2 so far described in syndromic craniosynostotic patients associated with sacrococcygeal defects suggest that this skeletal defect is not associated with specific FGFR2 mutations with no evidence of genetic heterogeneity.…”

“…Genotype-phenotype correlations of patients with FGFR2 mutations have showed that suture and limb development share common molecular pathways. If we take into account that all syndromic craniosynostotic cases with sacrococcygeal eversion also present tracheal alterations (Gonzales et al, 2005;Lapunzina et al, 2005;Lajeunie et al, 2006), we can speculate that an altered common signaling pathway is involved in these 2 defects.…”

Variable prenatal presentation of Pfeiffer syndrome: Suggested aids to prenatal sonographic diagnosis

“…Systematic analysis of the spine is a standard part of second‐trimester US screening, and the distal end of the sacrum and coccyx should be carefully analyzed in the context of suspected PS, even when fusion of vertebral bodies and posterior arches is absent on prenatal imaging. Differential diagnoses of syndromic craniosynostosis associated with a tail include Crouzon, Pfeiffer, Beare‐Stevenson, and acrocephalospondylosyndactyly syndromes …”

Pseudotail as a feature of microphthalmia with linear skin defects syndrome

“…A number of syndromes may be associated with the presence of skin appendages in the coccygeal area and these include chromosomal abnormalities, for example, Pallister-Killian syndrome, multiple congenital anomaly syndromes such as Simpson-Golabi-Behmel (Garganta and Bodurtha, 1992) and Crouzon syndrome (Lapunzina et al, 2005) and skeletal dysplasias such as metatropic dysplasia (O'Sullivan et al, 1998). They are usually lumbosacral protrusions consisting of normal or abnormal tissue, for example, prolongation of the coccygeal vertebrae, lipoma or glioma.…”