Pfeiffer syndrome is an autosomal dominant disorder classically characterized by craniosynostosis, facial dysmorphism and limb anomalies. The majority of cases are caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. A specific, rare mutation p.Pro252Arg, located between the second and third extracellular immunoglobulin-like domain of FGFR1, is associated with mild clinical signs. We report on a three-generation family with five members having a heterozygous FGFR1 p.Pro252Arg mutation. Phenotypic features within the family showed high variability from the apparently normal skull and limbs to the characteristic brachycephaly and digital anomalies. The typical features of Pfeiffer syndrome appeared only in the third generation allowing us to unveil the syndrome in several further family members in two previous generations. Variable expressivity can complicate the recognition of Pfeiffer syndrome, principally the mild type 1, requiring careful phenotyping and genetic counseling.

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Gonadal dysgenesis (GD) is a rare cause of differences of sex development (DSD) with highly variable clinical and genetic conditions. Although identification of the causative genetic alterations can offer a clearer prognosis and personalized management to patients, more than 50% of the DSD cases still do not have an accurate genetic diagnosis. NR5A1 (previously known as SF-1), is a transcriptional regulator of genes required for normal development and functional maintenance of the gonads and the adrenal glands. Nucleotide sequence variants of the NR5A1 gene have been reported in numerous patients with GD with or without adrenal failure, however, microdeletion or partial deletion in the NR5A1 gene have been described only in a few GD cases. In this case study, we present a subject with female phenotype, mild clitoromegaly, partial GD and normal adrenal function. Cytogenetic analysis revealed a 46,XY SRY + karyotype. Microarray analysis did not identify pathogenic copy number variations, nor did panel sequencing of the most common DSD genes. Subsequently, multiplex ligationdependent probe amplification (MLPA) was performed to test for small deletion/duplication of the most frequently affected genes associated with GD. Using this method, we have identified a novel heterozygous deletion involving exons 5 and 6 of the NR5A1 gene as the cause of abnormal sexual development of the patient. This report expands our knowledge about the range and pathogenetic role of NR5A1 mutations associated with partial gonadal dysgenesis in 46,XY DSD. Furthermore, our data emphasises the indispensable role of MLPA in the diagnosis of DSD with unclear etiology.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.