Introduction

In 1964, Pfeiffer described an acrocephalosyndactyly syndrome consisting of bicoronal craniosynostosis, midface deficiency, broad thumbs, broad big toes and partial and variable soft-tissue syndactyly of the hands and feet (1). Bu cümlenin aynısı bir başka makalede yayınlanmış ve referans farklı. Autosomal dominant inheritance with complete penetrance is characteristic, despite variable expressivity related to the presence or absence of syndactyly and its degree of severity. Based on the severity of the phenotype, Cohen proposed the division of Pfeiffer syndrome into 3 clinical subtypes (2). Classic Pfeiffer syndrome, designated type 1, involves individuals with mild manifestations, associated with normal neurological and intellectual development, generally has good outcome and can be found dominantly inherited. Type 2 consists of cloverleaf skull, Pfeiffer hands and feet, severe exorbitism, central nervous system involvement, elbow ankylosis or synostosis. Type 3 is similar to type 2 but without the cloverleaf skull. Types 2 and 3 have poor prognosis due to severe neurological compromise and various visceral anomalies, and they generally result in early death. To date, all cases of types 2 and 3 have only had sporadic occurrence.

We report a case of Pfeiffer syndrome type 1, with particular emphasis on the clinical presentation, differential diagnosis.

Case Report

The infant was the product of an uncomplicated, full-term gestation and normal vaginal delivery. The parents had a normal phenotype and were not consanguineous. The mother was 24 years and the father was 30 years old. The child had failure to thrive with a birth weight of 3.2 kg. On physical examination, acrocephaly, hypertelorism, antimongoloid slant of the eyes, flat nasal bridge, and low-set ears (Figure 1) were observed. The hands showed no abnormality. There was cutaneous syndactyly of the second and third toes bilaterally and the big toes were unusually broad. (Figure 2A, B). Computed tomography of the skull and brain showed bicoronal mild craniosynostosis. According to the above-mentioned findings, diagnosis of Pfeiffer syndrome was made clinically.

Discussion

The exact incidence of Pfeiffer syndrome is unknown, but is expected to be 1 in every 100 000 births in the Western population. Many cases had been reported in the literature (3,4). However, it is even rare in the Asian population, with few cases reported in Japan and Korea (5,6). Pfeiffer syndrome is known to be caused by mutations in exon IIIa or exon IIIc of the fibroblast growth factor receptor (FGFR)1 or 2 gene (7,8). Therefore, the disease is genetically heterogeneous. In Pfeiffer syndrome type 1, fresh mutations or autosomal dominance are the genetic disorders. In types 2 and 3, inheritance is sporadic. Pfeiffer syndrome type 1, which is named “classic,” involves individuals with mild manifestations including brachycephaly, midface hypoplasia, and toe abnormalities. This type is associated with normal intelligence and generally good outcome. Pfeiffer syndrome type 2 consists of cloverleaf skull, extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, developmental delay, and neurologic complications. Type 3 of this syndrome is similar to type 2, but without a cloverleaf skull. It should be noted that clinical overlap between the three types may occur (2). They may have other congenital anomalies of the upper airway, cleft palate, cleft lip, choanal atresia, fused vertebrae, imperforate anus, hydrocephalus, and Arnold-Chiari malformation (6). Our patient had none of these malformations. Our patient had mild clinical manifestations in favor of Pfeiffer syndrome type 1, which is an autosomal dominant condition consisting of broad thumbs and great toes as well as craniosynostosis usually of the coronal sutures (6,9).

The diagnosis of the Apert syndrome is appropriate rather than Pfeiffer syndrome if a patient has broad thumbs and syndactyly with bony fusion (10) or syndactyly of the second, third and fourth web spaces (11). However, clinical differential diagnosis has been confusing until now in relation with genetic findings because Pfeiffer mutation has been reported to occur in a patient with Apert syndrome (12), and identical mutations in the FGFR2 gene could cause both Pfeiffer syndrome and Crouzon syndrome phenotypes (13), as illustrated by the demonstration of both phenotypes of Apert and of Pfeiffer syndrome in experimental mice (14). Some authors have attempted to revise the classification for Apert, Carpenter, Crouzon, Jackson-Weiss, Pfeiffer and Saethre-Chotzen syndromes on a genetic basis (15-17). 

The prognosis depends on the severity of associated anomalies, mainly the severity of the central nervous system compromise. Patients with type 1 syndrome have, in general, a good prognosis. Patients with types 2 and 3 usually expire early in infant or childhood even though some may survive with aggressive medical and surgical management (6).