Perinatal/Neonatal Casebook &&&&&&&&&&&&&& Pfeiffer Syndrome, Type II

Thomas E. Herman, MD described in patients with Crouzon, Apert, Carpenter, and Pfeiffer Marilyn J. Siegel, MD syndromes, and most commonly in Pfeiffer syndrome.6 The great- toe-to-second-toe ratio has been considered to be helpful in suggesting the diagnosis of Pfeiffer syndrome. This is made by measuring the maximum width of the first toe divided by the CASE PRESENTATION maximum width of the second toe. In Pfeiffer syndrome, this ratio A full-term child was born by caesarean section because of is approximately 2 (1.7 to 2.2). Values below 1.7 are not breech presentation to a 25-year-old gravida 1, para 0 mother. suggestive of the diagnosis.1,5 The pregnancy had been uncomplicated. The Apgar scores were Pfeiffer syndrome type II is a sporadic condition consisting of 8 at 1 minute and 9 at 5 minutes. The child was dysmorphic clover leaf skull, severe orbital proptosis, broad thumbs and great with a clover leaf skull, orbital proptosis, elbow and knee toes, and ankylosis of the elbows.1 Severe ocular proptosis and contractures, and an anteriorly displaced anus. Exposure hydrocephalus are the most common complications.1 Other keratopathy of the cornea was present and the child had a malformations include malpositioned anus, intestinal malrotation, temporary tarsorraphy (suturing of the eyelids) to allow this to pelvic kidney, bifid scrotum, widely spaced nipples, and choanal heal. A skeletal survey (Figure 1) and cranial sonogram stenosis.5 Type III is essentially the same as type II but without a (Figure 2) were also performed. These demonstrated craniosy- clover leaf skull.1 The prognosis is also quite different between type nostosis, humeroradioulnar synostosis, vertebral anomalies, and I and the other two types. Type I has a relatively good prognosis digital anomalies. for intellectual outcome. The prognosis for types II and III is very poor, with death in childhood common.1 Possibly because of the poor prognosis in this presumed autosomal dominant condition, all cases of type II have been DENOUEMENT AND DISCUSSION sporadic. Congenital tracheal cartilaginous sleeve is a rare anomaly Elbow ankylosis, clover leaf skull, broad toes, and visceral anomalies of the trachea described in patients with Apert syndrome and Pfeiffer are typical of Pfeiffer syndrome, type II. Pfeiffer syndrome is the syndrome and carrying increased morbidity and mortality. In this second most common of the acrocephalosyndactyly syndromes anomaly, the tracheal ring cartilages are fused into a large solid tube (craniosynostosis and variable brachysyndactyly).1 The most of cartilage without pars membranacea posteriorly. This can result in common is Apert syndrome. Mutations at a very similar location in severe airway obstruction.8 the fibroblast growth factor receptor 2 have been found to cause both The presence of central nervous system anomalies, in addition to Pfeiffer syndrome and Apert syndrome.2 Antley-Bixler syndrome is a craniosynostosis, is the most important indicator of poor prognosis less common craniosynostosis syndrome with some findings for intellectual development.7 However, patients with clover leaf skull overlapping with Pfeiffer syndrome, type II, with which it has been anomaly appear to have a poor prognosis for intellectual confused.3,4 development even in the absence of other anomalies. At least one Pfeiffer syndrome type I is an autosomal dominant condition patient with a clover leaf skull underwent successful cranioplasty and consisting of broad thumbs and great toes and craniosynostosis subsequent normal intellect has been described.6 usually of the coronal sutures.1,5 Clover leaf skull is an Antley-Bixler syndrome is an autosomal recessive condition uncommon type of craniosynostosis. However, it has been associated with craniosynostosis (but not clover leaf skull), radiohumeral synostosis (but not complete elbow ankylosis), femoral bowing, and various visceral anomalies.3 However, the visceral anomalies in the Antley-Bixler syndrome are usually genital, e.g., clitoromegaly, fused labia, or hypoplastic labia.3 Although Mallinckrodt Institute of Radiology (T.E.H., M.J.S.), Washington University School of Medicine, anomalies of the fibroblast growth factor receptor 2 site have been 510 South Kingshighway Boulevard, St. Louis, MO. described in the Antley-Bixler syndrome, these patients also often Address correspondence and reprint requests to Thomas E. Herman, MD, Mallinckrodt Institute have an abnormality of steroidogenesis, suggesting that the disorder of Radiology, Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, MO 63100. may be digenic.3

566 Journal of Perinatology 2001; 21:565 – 567 Pfeiffer Syndrome Herman and Siegel

References 1. Cohen MM. Pfeiffer syndrome: update, clinical subtypes and guidelines for differential diagnosis. Am J Med Genet 1993;43:300–7. 2. Naski MC, Ornitz DM. FGF signaling in skeletal development. Pediatr Pathol Mol Med 1999;18:355–79. 3. Reardon W, Smith A, Honour JW, et al. Evidence for digenic inheritance in some cases of Antley-Bixler syndrome. J Med Genet 2000;37:26–32. 4. Kito H, Nogami H, Oki T, Arao K, Nagasaka M, Tanaka Y. Antley-Bixler syndrome: a disorder characterized by congenital synostosis of the elbow joint and the cranial suture. J Pediatr Orthop 1996;16:243–6. 5. Cohen MM, MacLean RE. Craniosynostosis: Diagnosis, Evaluation And Management. 2nd ed. Oxford, NY: Oxford University Press; 2000. p. 357. 6. Soekarman D, Fryns JP, vanden Berghe H. Pfeiffer acrocephalosyndactyly syndrome in mother and son with cloverleaf skull anomaly in the child. Genet Couns 1992;3:217–20. 7. Noetzel MJ, Marsh JL, Palkes H, Gado M. Hydrocephalus and mental retardation in craniosynostosis. J Pediatr 1985;107:885–92. 8. Noorily MR, Farmer DL, Belenky WMN, Philppart AI. Congenital tracheal anomalies in the craniosynostosis syndrome. J Pediatr Surg 1999;34:1036–39.

Figure 2. Cranial sonograms angled coronal (A) and sagittal (B) through the anterior fontanelle demonstrate the bulging of the temporal region appreciated on the skull radiographs. Otherwise, the sonogram is normal.

Figure 1. Radiographs from a skeletal survey. A and B, Anteroposterior and lateral skull radiographs. Typical clover leaf skull deformity is present with bulging in the temporal regions and over the convexity. The sagittal suture is open and the lambdoid and coronal sutures are synostotic. C, Anteroposterior right foot radiograph. The first toe is broad and short with abnormally shaped phalanges. D and E, Anteroposterior upper extremity radiographs. Completely osseous ankylosis is present at the elbow involving the radius, ulna, and humerus. The thumb is seen to be short and broad on the left hand. F, Anteroposterior chest and abdomen radiograph. A T6 sagittal cleft vertebral body is present. The axial skeleton is otherwise normal.

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