Variable Expressivity and Clinical Heterogeneity Can Complicate the Diagnosis and Management of Pfeiffer Syndrome

• DOI: 10.1097/scs.0b013e3182997df5
• Publication Date: 2013-09-13T05:17:19Z
• Authors: Nicholas Ettinger; Misti Williams; John A. Phillips
• Keywords: Expressivity

We report here a newborn female infant with striking features consistent severe Pfeiffer syndrome (PS). is rare craniofacial disorder that has an autosomal dominant mode of inheritance (OMIM 101600). Our patient had unexpected differences between her clinical and those predicted from genetic tests. The following were noted: exophthalmos, syndactyly, upper extremity contractures, relative macroglossia. A head computed tomography three-dimensional reconstruction showed she did not have craniosynostosis. Genetic tests included normal 46,XX karyotype chromosomal microarray revealed copy number gain at 14q23.1 as well loss 16p13.2. FGFR2 sequencing c.870G>T transversion in exon 8, which to encode Trp290Cys substitution. exophthalmos other typical PS without craniosynostosis most diagnosis type III. However, mutation reported be associated II includes kleeblatschädel (or “cloverleaf”) skull anomalies cardinal feature. patient’s lack this example variable expressivity. Such discrepancies the physical findings (phenotype) identified (genotype) association different mutations same gene (clinical heterogeneity) can present difficulties case management. Clinicians should guided by careful phenotyping rather than genotypic predictions alone.