Prenatal ultrasound diagnosis of a case of Pfeiffer syndrome without cloverleaf skull and review of the literature

Abstract

Pfeiffer syndrome is characterized by bilateral coronal craniosynostosis, midface hypoplasia, beaked nasal tip, broad and medially deviated thumbs and great toes. Originally, it was described in eight persons from three generations in a pedigree consistent with an autosomal dominant transmission. Since then, several reports have documented its high clinical and genetic heterogeneity. The condition is usually detected in the newborn period or later, and very few prenatal ultrasound diagnoses have been reported. We present a case of Pfeiffer syndrome prenatally diagnosed at 20 weeks' gestation, in which the sonographic features of craniosynostosis, hypertelorism associated with an extreme proptosis, and broad thumb led to the diagnosis, confirmed after termination of pregnancy by dysmorphological, pathological and radiological evaluation. DNA analysis of the fibroblast growth factor receptor 2 (FGFR2) showed a missense mutation consisting in a transversion G --> C at nucleotide 870. This led to a Trp290Cys amino acidic substitution. We discuss the relevant findings of our and previously published cases. Our report demonstrates that a careful sonographic examination can lead to an early prenatal diagnosis of Pfeiffer syndrome also in cases without cloverleaf skull.

Further evidence of association between mutations in FGFR2 and syndromic craniosynostosis with sacrococcygeal eversion

“…The mutation p.Trp290Cys has been described in 7 other cases of PS type 2 (Tartaglia et al, 1997;Schaefer et al, 1998;Ariga et al, 2001;Nazzaro et al, 2004;Lajeunie et al, 2006) and in 1 case of Crouzon's disease (Table 1). The description of the present patient reinforces the hypothesis that substitution of the Trp residue 290 by cysteine is mainly associated with a severe phenotype.…”

Craniosynostosis: prenatal diagnosis by 2D/3D ultrasound, magnetic resonance imaging and computed tomography.

“…Prenatal ultrasound diagnosis of Pfeiffer syndrome has been reported. Abnormalities in skull shape (brachycephaly, acrocephaly, cloverleaf skull), face (small nose, low nasal bridge and bulging front) and hands/feet (broad thumb/big toe) are usually the main phenotypic features [28,41]. The presence of "big eyes" or proptosis and hypertelorism may be also relevant [41,42].…”

“…Abnormalities in skull shape (brachycephaly, acrocephaly, cloverleaf skull), face (small nose, low nasal bridge and bulging front) and hands/feet (broad thumb/big toe) are usually the main phenotypic features [28,41]. The presence of "big eyes" or proptosis and hypertelorism may be also relevant [41,42]. Polyhydramnios has been associated with Pfeiffer type 1 and type 2, and close monitoring of pregnancy should be performed in these cases [32,44].…”

“…Pfeiffer syndrome (OMIM #101600) is characterized by craniosynostosis (mostly involving coronal sutures), midface hypoplasia (and other facial features secondary to synostosis) and anomalies of hand and feet (broad thumbs and great toes deviated away from other digits) [41]. It affects about 1 in 100,000 individuals and three subtypes have been identified [42,43].…”

Prenatal Sonographic Diagnosis of Familial Saethre-Chotzen Syndrome

“…[1][2][3][4] Saethre-Chotzen syndrome (Mendelian Inheritance in Man number 101400), also known as acrocephalosyndactyly type 3, is an autosomal dominant hereditary craniosynostosis disorder with a prevalence of 1 per 25,000 to 1 per 50,000. Surgical intervention within the first year of life is usually needed to prevent an increase in intracranial pressure, which can limit brain growth, and to minimize facial asymmetries.…”