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Pfeiffer Syndrome Type II Discovered Perinatally

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Pfeiffer Syndrome Type II Discovered Perinatally Diagnostic and Interventional Imaging (2012) 93, 785—789 CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector LETTER / Musculoskeletal imaging Pfeiffer syndrome type II discovered perinatally: Report of an observation and review of the literature a,∗ a a a H. Ben Hamouda , Y. Tlili , S. Ghanmi , H. Soua , b c b a S. Jerbi , M.M. Souissi , H. Hamza , M.T. Sfar a Unité de néonatologie, service de pédiatrie, CHU Tahar Sfar, 5111 Mahdia, Tunisia b Service de radiologie, CHU Tahar Sfar, 5111 Mahdia, Tunisia c Service de gynéco-obstétrique, CHU Tahar Sfar, 5111 Mahdia, Tunisia Pfeiffer syndrome, described for the first time by Pfeiffer in 1964, is a rare hereditary KEYWORDS condition combining osteochondrodysplasia with craniosynostosis [1]. This syndrome is Pfeiffer syndrome; also called acrocephalosyndactyly type 5, which is divided into three sub-types. Type I Cloverleaf skull; is the classic Pfeiffer syndrome, with autosomal dominant transmission, often associated Craniosynostosis; with normal intelligence. Types II and III occur as sporadic cases in individuals who have Syndactyly; craniosynostosis with broad thumbs, broad big toes, ankylosis of the elbows and visceral Prenatal diagnosis abnormalities [2]. We report a case of Pfeiffer syndrome type II, discovered perinatally, which is distinguished from type III by the skull appearing like a cloverleaf, and we shall discuss the clinical, radiological and evolutive features and the advantage of prenatal diagnosis of this syndrome with a review of the literature. Observation The case involved a male premature baby born at 36 weeks of amenorrhoea with multiple deformities at birth. The parents were not blood-related and in good health who had two other boys and a girl with normal morphology. The mother was 35 years old, it was her 4th pregnancy and 4th child. The pregnancy was poorly monitored and passed without any particular feature. Antenatal ultrasound examinations at 18 and 20 weeks of amenorrhoea found no morphological abnormalities. At 36 weeks of amenorrhoea the mother went into premature labour. Ultrasound at the beginning of labour found polyhydramnios with hydro- cephalus and the appearance of a cloverleaf skull (Fig. 1). Presentation was cephalic and delivery was vaginal without incident with an Apgar of 3 then 6 at the 5th and 10th minute respectively. ∗ Corresponding author. E-mail address: [email protected] (H. Ben Hamouda). 2211-5684/$ — see front matter © 2012 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.diii.2012.06.002 786 H. Ben Hamouda et al. Figure 3. Partial syndactyly between the second and third toes with broad, divergent big toes. Figure 1. Foetal ultrasound at 36 weeks of amenorrhoea: clover- leaf skull with hydrocephalus. Clinical examination of the baby on admission found hypotrophy with a birth weight of 2400 g, length of 50 cm, macrocephaly with a cranial circumference of 37 cm, res- piratory distress, facial dysmorphia with a cloverleaf skull, centro-facial hypoplasia, severe exophthalmia, low set ears, broad and divergent thumbs and big toes, ankylosis of the elbows and partial bilateral syndactyly between the second and third toes (Figs. 2 and 3). Radiological exploration of the skeleton showed bilateral coronal craniosynostosis, radio- humeral synostosis and duplication of the first phalange of the thumbs (Figs. 4—6). A cerebral and cranio-facial CT scan showed hydrocephalus, intraventricular haemorrhage, mal- formation of the bones of the skull with no coronal sutures (Figs. 7 and 8). Evolution was marked by aggravation of the respiratory distress and the patient died on the third day of life. Figure 4. X-ray of the skull: craniosynostosis of the coronal sutures. Figure 5. X-ray of the elbow: radio-humeral synostosis. Figure 2. Cloverleaf skull with bilateral exophthalmia. Pfeiffer syndrome type II discovered perinatally 787 Discussion The exact incidence of Pfeiffer syndrome is unknown. It is estimated to be 1/100,000 births [3]. In 1993, Cohen [4] classified Pfeiffer syndrome into three sub- types. This classification is useful both clinically and for prognosis. Type I is the classic Pfeiffer syndrome with autosomal dominant transmission. It includes patients who have moderate dysmorphia with broad thumbs and big toes, centro-facial hypoplasia and craniosynostosis of the coronal sutures. The intellectual development of these patients is generally normal and their prognosis is good [3]. Type II, our patient’s case, presents as sporadic cases. It combines a cloverleaf skull, severe exophthalmia, ankylosis or synostosis of the elbow, broad thumbs and big toes and neurological complications. Hydrocephalus, as seen in our patient, is the most common neurological complication [2]. On the other hand, the ventricular haemorrhage found in our patient was very probably related to severe neonatal stress Figure 6. X-ray of the hand: duplication of the 1st phalange of and has never been described as a complication of Pfeiffer the thumb. syndrome. Other abnormalities can be associated with this Figure 7. Axial cerebral CT scan: hydrocephalus with malformation of the skull (a, b). Figure 8. Cranio-facial CT scan with three-dimensional reconstruction: wide open metopic suture with absence of coronal sutures (a, b). 788 H. Ben Hamouda et al. Table 1 Clinical characteristics of sub-types of Pfeiffer syndrome. Type Main characteristics Associated signs Life span Intellectual development Type I Craniosynostosis Deafness Compatible Normal with life Centro-facial hypoplasia Hydrocephalus Broad thumbs Broad big toes Brachydactyly Variable syndactyly Type II Cloverleaf skull Atresia or stenosis of the Early death Psychomotor and external auditory canal mental retardation Severe exophthalmia Atresia or stenosis of the posterior apertures of the nose Broad thumbs Laryngotracheal abnormalities Broad big toes Hydrocephalus Brachydactyly Convulsion Variable syndactyly Cerebral or cerebellar hernia Ankylosis of the elbow Hydronephrosis Kidneys in pelvic position Bifid scrotum Intestinal malrotation Malposition of the anus Hypoplastic gall bladder Type III Craniosynostosis Atresia or stenosis of the Early death Psychomotor and posterior apertures of the nose mental retardation Severe exophthalmia Laryngotracheal abnormalities Broad thumbs Hydrocephalus Broad big toes Convulsion Brachydactyly Variable syndactyly Ankylosis of the elbow syndrome and are shown in Table 1 [2,5,6]. Type III resem- Moreover, X-rays of the feet show broad, short big toes bles type II, but the patient does not have a cloverleaf skull. with incorrectly formed phalanges. X-rays of the hands Absence of this sign can make diagnosis more difficult. The show broad, short thumbs. X-rays of the upper limbs may prognosis for Pfeiffer syndrome types II and III is very poor, show ankylosis of the elbows involving the radius, ulna and with a high risk of early death of the child through neuro- humerus. logical and respiratory complications [3]. The intellectual Transfontanellar ultrasonography is the primary imaging development of patients with a cloverleaf skull seems to technique in the newborn for detecting congenital hydro- be poor even if there are no other neurological abnormali- cephalus, which is the most common abnormality in Pfeiffer ties [2]. This is explained by the craniosynostosis resulting syndrome type II. However, cerebral MRI is the examination in insufficient brain development [3]. of choice for a complete assessment of the cerebral lesions The diagnosis of Pfeiffer syndrome is essentially clinical. allowing evaluation of any hydrocephalus and the status of However, radiological exploration can confirm the skeletal the cerebral parenchyma [8]. abnormalities of the syndrome and look for associated mal- Molecular genetics has recently provided better under- formations. X-rays of the skull show the major malformation standing of the molecular basis of Pfeiffer syndrome, which of the cranium and the coronal craniosynostosis. In Pfeiffer is due to mutations of exon IIIa or IIIc of fibroblast growth syndrome type II they show the cloverleaf appearance of the factor receptor 1 (FGFR1) located on chromosome 8p11.2- skull with bulging in the temporal regions and on the con- p11 or of FGFR2 located on chromosome 10q26 [3,9]. Indeed, vexity, a widely open sagittal suture and synostosic coronal the less serious forms, seen as Pfeiffer syndrome type I, are sutures [2]. Indeed, these abnormalities are shown better by related to mutation of the FGFR1 gene while the more severe a cranio-facial CT scan with three-dimensional reconstruc- forms, seen as types II and III, are linked to mutation of the tion which must be performed as soon after birth as possible, FGFR2 gene. The FGFR1 and FGFR2 genes are involved in the as was the case for our patient. This imaging technique is response of the cell to its environment probably by way of a very useful, because it provides direct visualisation of the signal inducing maturation or division of the cell. Mutation sutures of the cranial vault and shows the cranio-facial bony of this gene prolongs this signal which may be the cause of anatomy [7]. early maturation of bone cells and consequently of fusion of Pfeiffer syndrome type II discovered perinatally 789 the bones of the skull, arms and feet [3]. The same mutation Finally, a molecular biology analysis can provide a pre- of the FGFR gene has been identified in the Jackson-Weiss cise diagnosis
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