Prenatal diagnosis of Pfeiffer syndrome and role of three-dimensional ultrasound: case report and review of literature

Abstract

Purpose/aim of the study: We report a rare case of autosomal dominant genetic syndrome "Pfeiffer", which is part of the group of acrocephalosyndactyly, with an annual incidence <1/100,000. Three forms are known. Type I is the less common form and it is characterized by moderate–severe mediofacial hypoplasia usually with normal cognitive development. Conversely, types 2 and 3 are more common and they are associated with more severe signs and complications with a more unfavorable prognosis. The type 3 form due to the presence of a cloverleaf skull distinguishes type 2.

Materials and methods: Thirty-eight-year-old primigravida was referred to our center, at 28 weeks of gestation due to borderline ventriculomegaly, macrocrania, and a short femur. First trimester screening for chromosomopathies and CF-DNA was low risk; II trimester screening ultrasound showed the presence of “short femur” and macrocrania.

Result: Our ultrasound evaluation, assisted by 3D ultrasound, showed cloverleaf skull, turricephaly, moderate ventriculomegaly (13 mm), hypertelorism and exophthalmos, low ear implantation, mild rhizomelia. Ultrasound depicts Pfeiffer syndrome or other acrocephalosyndactyly syndromes (Apert syndromes, Saethre-Chotzen) or other syndromic forms of craniosynostosis like Crouzon syndrome. The NGS panel for molecular analysis of genes involved in skeletal dysplasias showed the mutation of the FGFR2 gene, de novo.

Conclusions: Using three-dimensional (3D) ultrasound, it is easier to distinguish rare syndromes characterized by facial dysmorphisms such as exophthalmos, mediofacial hypoplasia, and craniosynostosis.

Keywords:

• Craniosynostosis
• Pfeiffer syndrome
• prenatal diagnosis
• FGFR 1
• FGFR 2
• cloverleaf skull

Acknowledgements

Ethical approval and consent to participate: There was no formal approval of the Ethics Committee, but the procedures were carried out in accordance with the Declaration of Helsinki, as revised in 2013.

Consent for publication: Written informed consent for the anonymous publication of information relating to the disease is.

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

This research project was supported in part by the Unit of Obstetrics and Gynaecology – University of Bari Aldo Moro, Bari, Italy.