Prenatal Diagnosis of Cloverleaf Skull: Watch the Hands!

Abstract

Pfeiffer syndrome is an extremely rare autosomal-dominant condition whose prenatal diagnosis has only been reported 6 times, mainly on the basis of a fetal cloverleaf skull deformity. Three types have been described, each with a different prognosis. This case report stresses the need to thoroughly analyze the fetus and particularly the fetal hands in case of prenatal observation of a cloverleaf skull. The discovery of characteristic hand abnormalities allowed the early prenatal detection of type 2 Pfeiffer syndrome in our patient.

Variable prenatal presentation of Pfeiffer syndrome: Suggested aids to prenatal sonographic diagnosis

“…Anomalies of the thumbs and big toes are, with craniosynostosis, major diagnostic clues for PS. This can include syndactyly, as in one of our cases, but this is not a common finding and was only found in 4 or 23 cases reviewed in the literature …”

“…Diagnosis in our series was made around 22–23 WG which is earlier than the mean gestational age of 27 weeks reported in the literature at which PS is suspected on prenatal US . In “classical” cases with a cloverleaf skull and abnormal extremities the diagnosis of PS has been reported as early as 18 and 20 WG …”

“…Other craniosynostosis syndromes such as Apert, Crouzon, and Jackson‐Weiss syndromes should be considered following the detection of fused sutures and digital anomalies, but with the finding of adducted broad thumbs on prenatal imaging, the diagnosis of PS is more likely as with 3 out of our 4 fetuses (Table ).…”

“…8 In "classical" cases with a cloverleaf skull and abnormal extremities 9,10 the diagnosis of PS has been reported as early as 18 and 20 WG. [11][12][13] Craniosynostosis is defined as the premature closure of 1 or more cranial sutures. Anomalies of the thumbs and big toes are, with craniosynostosis, major diagnostic clues for PS.…”

Prenatal Diagnosis of Apert Syndrome with Cloverleaf Skull Deformity Using Ultrasound, Fetal Magnetic Resonance Imaging and Genetic Analysis

“…The prenatal craniofacial features in combination with the pronounced polysyndactyly of all extremities enabled us to narrow down the differential diagnosis to abnormalities that also include the upper and lower limbs such as Apert, Carpenter and Pfeiffer syndrome. Especially the association of Pfeiffer syndrome with a cloverleaf skull deformity is relatively common [11,12] . In addition, the presence of a mild ventriculomegaly made the Pfeiffer syndrome an important differential diagnosis.…”