Pfeiffer syndrome (PS) is a rare autosomal dominant genetic disorder characterized by craniosynostosis, broad thumbs / toes. Here, we report a case of PS type 2 with increased nuchal translucency in early trimester.

BACKGROUND Pfeiffer syndrome (PS) is a fibroblast growth factor receptor (FGFR)-associated craniosynostosis syndrome, characterized by abnormally broad and medially deviated thumbs and great toes. Tracheal cartilage sleeve (TCS) is associated with several FGFR-associated craniosynostosis syndromes, including PS. TCS is an airway malformation in which the tracheal cartilage rings fuse with each other to form a sleeve of cartilage. CASE REPORT The patient was a 4-year-old girl with PS, TCS, and abnormal hyperplasia of non-fused intrapulmonary cartilages. The patient showed cranial dysplasia on prenatal ultrasonography. At birth, a cloverleaf skull in association with hydrocephalus and digital malformations was apparent. These findings were consistent with PS type 2. The diagnosis of PS type 2 was confirmed from a genetic test detecting a FGFR2 mutation (Y340C). During the clinical course, she underwent several surgeries, including ventriculoperitoneal shunts, sequential cranioplasty surgeries, and tracheotomy due to upper airway abnormalities. At 4 years old, she died of multiple organ failure following aspiration pneumonia. The autopsy revealed that the tracheal cartilages had fused with each other, resulting in a condition called TCS, in which the cartilage rings and tracheal ligaments were absent. The lungs were poorly aerated, and the dilated bronchi had thickened walls surrounded by many cartilage fragments, mainly at the hilum. These cartilages tended to overlap at both ends, did not fuse, and were greatly altered in size and shape. CONCLUSIONS We report the results of autopsy for PS with the first histopathological findings for the lungs and other visceral organs.

Pfeiffer syndrome is a rare genetic disorder with heterogenous phenotype and prognosis. Due to its diverse clinical presentation, it can easily be misdiagnosed. Where genetic testing still remains a challenge, antenatal sonogram can aid in early diagnosis. The cranioorbito-faciostenosis demands aggressive management to permit survival instead of uniform early demise.

Pfeiffer syndrome is a rare autosomal dominant inherited disorder associated with craniosynostosis, midfacial hypoplasia, and broad thumbs and toes. The syndrome has been divided into three clinical subtypes based on clinical findings. This review will specifically examine the most severe type, Pfeiffer syndrome type 2, focusing on its genetics and molecular biology. This subtype of the syndrome is caused by de novo sporadic mutations, the majority of which occur in the fibroblast growth factor receptor type 1 and 2 (FGFR1/2) genes. There is not one specific mutation, however. This disorder is genetically heterogeneous and may have varying phenotypic expressions that in various cases have overlapped with other similar craniosynostoses. A specific missense mutation of FGFR2 causing both Pfeiffer and Crouzon syndromes has been identified, with findings suggesting that gene expression may be affected by polymorphism within the same gene. Compared to other craniosynostosis-related disorders, Pfeiffer syndrome is the most extreme phenotype, as the underlying mutations cause wider effects on the secondary and tertiary protein structures and exhibit harsher clinical findings.

Pfeiffer syndrome is a rare autosomal dominant inherited disorder associated with craniosynostosis, midfacial hypoplasia, and broad thumbs and toes. The syndrome has been divided into three clinical subtypes based on clinical findings. This review will specifically examine the most severe type, Pfeiffer syndrome type 2, focusing on its genetics and molecular biology. This subtype of the syndrome is caused by de novo sporadic mutations, the majority of which occur in the fibroblast growth factor receptor type 1 and 2 (FGFR1/2) genes. There is not one specific mutation, however. This disorder is genetically heterogeneous and may have varying phenotypic expressions that in various cases have overlapped with other similar craniosynostoses. A specific missense mutation of FGFR2 causing both Pfeiffer and Crouzon syndromes has been identified, with findings suggesting that gene expression may be affected by polymorphism within the same gene. Compared to other craniosynostosis-related disorders, Pfeiffer syndrome is the most extreme phenotype, as the underlying mutations cause wider effects on the secondary and tertiary protein structures and exhibit harsher clinical findings.