*Both authors contributed equally to this work
1 - Serviço de Genética Médica, Área de Pediatria, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal;
2 - Unidade de Cuidados Intensivos Neonatais, Área de Pediatria, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
- Reunião nacional – 3.as Jornadas de Doenças Ósseas Raras, sob a forma de comunicação oral
Introduction: Pfeiffer syndrome (PS) is an autosomal dominant skeletal disorder, classically characterized by craniosynostosis, facial dysmorphisms, and digital anomalies. PS is caused by pathogenic variants of FGFR genes. In last years, a wide range of manifestations, with or without craniosynostosis, has been reported. Additionally, extra-skeletal manifestations including eye, auricular, respiratory, cardiovascular, gastrointestinal, and genitourinary anomalies have been observed.
Case report: A late premature male neonate was transferred from Azores to a tertiary NICU due to feeding intolerance secondary to partial duodenal membrane, requiring surgical correction. He also had deviated great toes, and syndactyly of 2/3 toes on the left, and 2/3/4 on the right, which prompted genetic referral. He had no other dysmorphic features. Evaluation of family history revealed syndactyly and deviated broad thumbs and toes in four generations (father, cousin, grandfather, and great‑grandfather), and second cousin diagnosed with PS, associated to a common FGFR1 pathogenic variant (p.(Pro252Arg)). We hypothesized that the proband congenital anomalies and the familial digital anomalies were manifestations of the PS spectrum, being all related to the familial FGFR1 variant. Molecular analysis of proband and his father confirmed the presence of p.Pro252Arg variant. Craniosynostosis was excluded, and genetic counselling was provided to parents.
Conclusion: Variable expressivity can complicate the recognition of PS. Careful phenotyping and acknowledgment of family history are necessary. Genetic counselling is also required to inform the PS families about the 50% risk of transmission, the possibilities of the anomalies that may occur in future pregnancies, and the extreme clinical variability.
Palavras Chave: FGFR1 variant, Pfeiffer syndrome, craniosynostosis