Pediatr Radiol DOI 10.1007/s00247-014-2966-4


Pai syndrome: challenging prenatal diagnosis and management Marie Blouet & Frédérique Belloy & Corinne Jeanne-Pasquier & Nathalie Leporrier & Guillaume Benoist

Received: 9 August 2013 / Revised: 29 January 2014 / Accepted: 5 March 2014 # Springer-Verlag Berlin Heidelberg 2014

Abstract Pai syndrome is a rare disorder that includes midline cleft lip, pericallosal lipoma and cutaneous polyp of the face. We report a case of prenatal diagnosis using sonography and MRI. We emphasize the importance of facial examination with prenatal association of midline cleft lip and pericallosal lipoma in making the diagnosis of Pai syndrome.

has rarely been described. We report a case of a prenatally diagnosed fetus with multimodal prenatal imaging methods.

Keywords Pai syndrome . Pericallosal lipoma . Midline cleft lip . Cutaneous polyp . Fetal magnetic resonance imaging . Ultrasound . Fetus

A 25-year-old woman, gravida 2 para 1, was referred for evaluation at 24 weeks’ gestation for midline cleft lip and abnormality of the corpus callosum detected in the fetus on routine second-trimester US scan. Neither familial history of cleft lip nor congenital abnormalities was reported. Parents were healthy and unrelated. The woman’s first child had no abnormalities. Fetal dedicated neurosonogram showed partial agenesis of the corpus callosum and a pericallosal lipoma (Fig. 1). A midline cleft lip without any palatal defect was confirmed on 3-D ultrasonography but no other facial anomaly was seen (Fig. 1). The woman was lost to follow-up for 2 months. At 31 weeks of gestation, the woman requested information about the fetal abnormalities. Psychological follow-up was initiated. Amniocentesis was performed for fetal karyotyping (46,XX). A multidisciplinary decision was made to confirm the anomalies with fetal MRI. T1-weighted fetal MR examination without fat suppression confirmed the agenesis of the corpus callosum splenium and the fatty composition of the anterior pericallosal lipoma, which was tubulonodular type, without any other cerebral abnormalities (Fig. 2). Examination of the cephalic shape enabled additional visualization of a bifid nose as well as two facial polyps (one nasal at the left nostril and one located frontally) (Fig. 2). This association of facial abnormalities, pericallosal lipoma and medial cleft suggested a Pai syndrome. The woman was counseled on the potential mental deficiencies associated with agenesis of the corpus callosum and the tubulonodular pericallosal lipoma together with the physical limitations and surgical outlook.

Introduction In 1987 Pai et al. [1] reported a new syndrome of frontonasal malformation. Since then prenatal diagnosis of Pai syndrome M. Blouet : F. Belloy Department of Radiology, Centre Hospitalier Universitaire de Caen, Caen, France M. Blouet : N. Leporrier : G. Benoist University of Lower Normandie, Caen, France C. Jeanne-Pasquier Department of Pathology, Centre Hospitalier Universitaire de Caen, Caen, France N. Leporrier Department of Genetics, Centre Hospitalier Universitaire de Caen, Caen, France G. Benoist (*) Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire, Pôle Femmes-Enfants, Avenue de la côte de Nacre, 14000 Caen, France e-mail: [email protected] G. Benoist e-mail: [email protected]

Case report

Pediatr Radiol Fig. 1 Fetal sonography at 24 weeks’ gestation. a 2-D Doppler US image of the midsagittal section (vaginal probe) shows anterior pericallosal lipoma (arrow) and partial agenesis of the corpus callosum. b 3-D US image shows midline cleft lip (arrow), without any evidence of other facial anomalies

Termination of the pregnancy was performed at parental request at 35 weeks of gestation (in accordance with the French law). After informed consent, a fetal postmortem examination was performed, including standard

Fig. 2 Fetal MRI at 32 weeks’ gestation. a Sagittal T2-weighted MR image shows partial agenesis of the corpus callosum. b Axial T1-weighted MR image without fat suppression shows fatty composition of pericallosal lipoma with hyperintense signal (arrow). c Axial T2-weighted MR image shows bifid nose (arrow). d Parasagittal T2-weighted MR images show facial polyp (arrow)

radiographic and neuropathological examination. All of the prenatal findings were confirmed without any additional abnormalities (Fig. 3), confirming the diagnosis of Pai syndrome.

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Fig. 3 Post-mortem examination at 35 weeks of gestation. a Photograph of fetal face confirms the bifid nose and the facial polyps. b Gross pathology. The cut surface shows the anterior tubulonodular pericallosal

lipoma. c Histology of the lipoma shows mature cellular adipocytes, with no cellular atypia (hematoxilyn and eosin stain, ×10)


upper lip, nasal skin masses, and lipoma of the corpus callosum. Thirty-six postnatally diagnosed cases have been described, 20 of which were male (55%, gender ratio: 1.2) [4]. Castori et al. [5] suggested minimum diagnostic criteria: one or more hamartomatous nasal polyps plus median cleft lip (with or without cleft alveolus) or midanterior alveolar process congenital polyp. These criteria are consistent with reports in the literature. Of the 36 reported cases, all had fronto-nasal polyp, 97% had nasal polyp, and midline cleft lip was found in 80% [4]. Lederer et al. [6] added one diagnostic criterion: pericallosum lipoma, also observed in our case and reported in 85% (23/36) of the cases described in the literature. Recently, however, Ocak and al. [2] reported a prenatal detection of a Pai syndrome without cleft lip and palate. Our case met all main diagnostic criteria plus bifid nose, already described in two cases [4]. Szeto et al. [7] reported a case of Pai syndrome in 2005 and reviewed the six previously published cases and reported no neurological impairment, and psychomotor development was normal in all cases. Therefore the decision to terminate the pregnancy in our case was based on the presence of the tubulonodular lipoma, which is more often associated with severe commissural dysgenesis and less favorable outcome. There was also major facial dysmorphology in our case and the potential for successful corrective surgery was limited. MRI confirmed the pericallosal lipoma and the corpus callosum agenesis in our case but also highlighted facial anomalies such as a bifid nose and facial skin masses. These anomalies had not been seen with 2-D and 3-D first ultrasonography screening. However the association of pericallosal anterior lipoma and medial cleft should lead to careful facial screening, with major role for 3-D ultrasonography. Our case showed normal female karyotype (46,XX). Castori et al. [5] mentioned several hypotheses such as chromosome

Very few cases of Pai syndrome diagnosed prenatally have been described [2]. Pai syndrome is usually diagnosed at birth. This case highlights the importance of facial fetal examination in complex associated findings suspected by US examination. Furthermore it illustrates the usefulness of MRI for further evaluation of fetal shape as well as fetal face when indicated by 3-D ultrasound. Pericallosal lipoma is a rare tumor that represents 0.06– 0.46% of prenatally described intracranial lesions [1, 3]. It is related to an over-proliferation of the fat cells in the leptomeninx. There are two types of pericallosal lipomas based on imaging. The tubulo-nodular lipoma is the most common one, rounded or lobular, thick and anteriorly situated, it is more frequently associated with extensive callosal and often fronto-nasal anomaly. The second and less common type is the curvilinear lipoma, elongated or curvilinear, thin and posteriorly situated. The first condition is frequently associated with intracerebral malformations, mainly agenesis of the corpus callosum, which could be related to an interference with its natural growth and is more often associated with severe commissural dysgenesis and less favorable outcome. Several cases of prenatal diagnosis of pericallosal lipoma by ultrasonography have been described, and the largest series of seven cases was reported by Ickowitz et al. [3]. MRI shows the fatty content of the lipoma as hypointense signal on T2weighted sequences and spontaneous hyperintense signal on T1-weighted sequences without fat suppression. MRI also gives information about the extent of the lipoma and any associated anomaly of the corpus callosum. These findings together with the midline cleft lip were highly suggestive of Pai syndrome. The main elements of this syndrome, first described by Pai et al. [1] in 1987, are median cleft of the

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imbalances, nongenetic factors, X-linked recessive and de novo mutations with dominant autosomal trait, but they also found that the overall recurrence risk for parents with a previous child with Pai syndrome appears very low [5]. We describe a rare case of prenatal diagnosis of Pai syndrome that included the modified diagnostic criteria suggested by Lederer et al. [6] This diagnosis was made with the use of multimodality imaging. The midline cleft lip and pericallosal lipoma were discovered by ultrasonography in our case and confirmed by MRI. MRI also showed fronto-nasal polyps and bifid nose that were overlooked on the 3-D ultrasonography. Therefore, the association of pericallosal lipoma and corpus callosum agenesis indicates the possibility of Pai syndrome and should lead to detailed analysis of the fetal face with 3-D ultrasonography.

Conflicts of interest None.

References 1. Pai GS, Levkoff AH, Leithiser RE Jr (1987) Median cleft of the upper lip associated with lipomas of the central nervous system and cutaneous polyps. Am J Med Genet 26:921–924 2. Ocak Z, Yazicioglu HF, Aygun M et al (2013) Prenatal detection of Pai syndrome without cleft lip and palate: a case report. Genet Couns 24:1–5 3. Ickowitz V, Eurin D, Rypens F et al (2001) Prenatal diagnosis and postnatal follow-up of pericallosal lipoma: report of seven new cases. AJNR Am J Neuroradiol 22:767–772 4. Chousta A, Ville D, James I et al (2008) Pericallosal lipoma associated with Pai syndrome: prenatal imaging findings. Ultrasound Obstet Gynecol 32:708–710 5. Castori M, Rinaldi R, Bianchi A et al (2007) Pai syndrome: first patient with agenesis of the corpus callosum and literature review. Birth Defects Res A Clin Mol Teratol 79:673–679 6. Lederer D, Wilson B, Lefesvre P et al (2012) Atypical findings in three patients with Pai syndrome and literature review. Am J Med Genet A 158:2899–2904 7. Szeto C, Tewfik TL, Jewer D et al (2005) Pai syndrome (median cleft palate, cutaneous nasal polyp, and midline lipoma of the corpus callosum): a case report and literature review. Int J Pediatr Otorhinolaryngol 69:1247–1252

Pai syndrome: challenging prenatal diagnosis and management.

Pai syndrome is a rare disorder that includes midline cleft lip, pericallosal lipoma and cutaneous polyp of the face. We report a case of prenatal dia...
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