Journal of Perinatology (2013) 33, 572–573 r 2013 Nature America, Inc. All rights reserved. 0743-8346/13 www.nature.com/jp PERINATAL/NEONATAL CASE PRESENTATION A unique variant of Poland–Mobius syndrome with and a 3q23 gain

A Flores1, JR Ross2, TG Tullius Jr2 and GS Levin1 1Division of Neonatology, Department of Pediatrics, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, TX, USA and 2Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, TX, USA

short and lacking cartilage. The overlying soft tissues and musculature The combined Poland and Mobius syndrome occurs rarely and with a wide including a large portion of the left were absent or range of features. There is no consensus on the etiology of this syndrome; hypoplastic. was dysplastic and described as single-ossified familial, sporadic cases and likely environmental insult cases have been reported. mass with ventral angulation. Dextrocardia without situs inversus was This sporadic case represents a unique variant in the spectrum of this syndrome. noted in this imaging study and in the echocardiogram. No other Journal of Perinatology (2013) 33, 572–573; doi:10.1038/jp.2012.92 structural heart abnormalities were seen. Brain magnetic resonance Keywords: Poland–Mobius syndrome; sporadic; dextrocardia; imaging showed a large anterior fontanel and normal brain chromosome 3q23 architecture. Abdominal ultrasound showed a left moderate hydronephrosis and hydroureter. A voiding cystourethrogram done before discharge was normal. Swallowing study was abnormal. Case Chromosomal microarray reported a copy number gain of 0.3 Mb in Our patient was born at 39 weeks gestation with a birth weight of chromosome 3q23. Newborn screen was normal. A multidisciplinary 3360 g to a 36-year-old G3P0 (0020) Caucasian mother by caesarian team is involved in this patient’s care. section secondary to breech presentation. The mother denies any history of traumatic injuries and toxic habits. There is no history of Discussion consanguinity and past medical histories were noncontributory. APGAR scores were 8 and 8 at 1 and 5 min, respectively. Our patient presented with right facial weakness, left chest wall Physical examination was significant for multiple deformity and left lower limb abnormality. This constellation of abnormalities. He had right facial weakness characterized by abnormalities falls under the spectrum of Poland–Mobius inability to completely close his right eye and drooping of the right syndrome. The essential features of Poland syndrome are unilateral corner of the mouth (Figure 1). Abduction was not appreciated in absence or hypoplasia of the pectoralis muscles with a majority of either eye. His forehead was wide and the anterior fontanel patients having malformations and hypoplasia of the ipsilateral 1 B measured 6.5 Â 6 cm. He had high arched palate and limbs. The incidence of Poland’s syndrome is 1:20 000 to 32 000.2 Males are more affected than females, and the right chest micrognathia. The left chest was deformed and associated with 3 lung herniation during inspiration (Figure 1). Some of the left is predominantly deformed. Mobius syndrome displays a broad spectrum of facial paralysis often associated with the inability to were malformed and the pectoralis muscle appeared absent. 4 Nipples were widely spaced and the left was mildly hypoplastic. abduct the eye. Rarely, a patient may manifest a combination Apical impulse was heard on the right side of the chest. The left of features found in these two syndromes, hence the term Poland–Mobius syndrome.5,6 The prevalence has been estimated was slightly weaker and mildly hypoplastic. Examination of 7 the lower extremities demonstrated a left (Figure 1). to be 1:500 000. There are many other associated defects and Plain film of the chest showed dextrocardia and left 3rd to 5th ribs little consensus as to what constitutes the full syndrome. The etiology remains unclear despite multiple proposed theories. that were thinned and incomplete anteriorly; the sternum was 2 dysplastic without ossification centers. Thoracic computed tomography Darian et al. extensively reviewed familial cases of Poland’s confirmed the underdevelopment of the left ribs described as thin, syndrome and suggested an autosomal dominant gene with variable penetrance in these familial cases. Reports of Mobius Correspondence: Dr A Flores, Division of Neonatology, Department of Pediatrics, Texas Tech syndrome occurring in families have been reported but the pattern University Health Sciences Center, Paul L. Foster School of Medicine, 4800 Alberta, El Paso, of inheritance remains elusive. Gene loci localized in chromosomes TX 79905, USA. E-mail: angela.fl[email protected] 3q21–q22 and 10q21.3–q22.1 were identified in two Dutch 8,9 Received 30 April 2012; revised 13 June 2012; accepted 14 June 2012 families with Mobius syndrome. Our patient was noted to have a A unique variant of Poland–Mobius syndrome A Flores et al 573

described as type II or form fruste .3 He has a large anterior fontanel but no evidence of hypothyroidism, a feature that has not been described to our knowledge. The presence of skeletal abnormalities in Mobius syndrome was initially thought to be associated with sporadic cases and a recurrence risk of 2%.14 However, this may not always be the case as Graziadio et al.15 recently reported a familial case with skeletal findings. Our case is likely a sporadic occurrence given the negative family history, absence of consanguinity and uneventful prenatal course.

Conflict of interest The authors declare no conflict of interest.

Acknowledgments We gratefully acknowledge Dr Chetan Moorthy for the imaging studies done on this patient.

Figure 1 Physical examination shows right facial weakness, asymmetry of chest wall, left lung herniation, normal hand and left clubfoot. References 1 David TJ. Nature and etiology of the Poland anomaly. N Engl J Med 1972; 287(10): gain in chromosome 3q23 close to the gene loci mentioned earlier; 487–489. however, there is no definitive evidence of a specific gene linked to 2 Darian VB, Argenta LC, Pasyk KA. Familial Poland’s syndrome. Ann Plast Surg 1989; the combined syndrome of Poland–Mobius. The significance of 23(6): 531–537. this finding will need further research. Of note, Rojas-Martinez 3 Al-Qattan MM. Classification of hand anomalies in Poland’s syndrome. Br J Plast Surg 10 2001; 54(2): 132–136. et al. reported a boy with Poland–Mobius syndrome born to a 4 Van Allen MW, Blodi FC. Neurologic aspects of the Mobius syndrome. A case study with mother with Poland syndrome, which brings to question whether electromyography of the extraocular and facial muscles. Neurology 1960; 10: 249–259. Poland and Mobius are independent syndromes or manifestations 5 Sugarman GI, Stark HH. Mobius syndrome with Poland’s anomaly. J Med Genet 1973; of the same variable syndrome. 10(2): 192–196. Trauma and exposure to toxic substances have also been 6 Bosch-Banyeras JM, Zuasnabar A, Puig A, Catala M, Cuatrecasas JM. Poland-Mobius implicated, and case reports have described the association of this syndrome associated with dextrocardia. J Med Genet 1984; 21(1): 70–71. 7 Puvabanditsin S, Garrow E, Augustin G, Titapiwatanakul R, Kuniyoshi KM. Poland- syndrome with attempted abortions, intrauterine exposure to Mobius syndrome and cocaine abuse: a relook at vascular etiology. Pediatr Neurol 1,7,11 ergonovine maleate, cocaine and misoprostol. A vascular 2005; 32(4): 285–287. etiology proposed by Bavinck and Weaver makes the case that 8 Kremer H, Kuyt LP, van den Helm B, van Reen M, Leunissen JA, Hamel BC et al. specific location of disruption of blood flow in the subclavian and Localization of a gene for Mobius syndrome to chromosome 3q by linkage analysis in a vertebral arteries as well as its branches results in a specific Dutch family. Hum Mol Genet 1996; 5(9): 1367–1371. 9 Verzijl HT, van den Helm B, Veldman B, Hamel BC, Kuyt LP, Padberg GW et al. A second anomaly (that is, complete or partial occlusion of the vertebral gene for autosomal dominant Mobius syndrome is localized to chromosome 10q, in a arteries may cause ischemia to the motor nuclei of cranial VI and Dutch family. Am J Hum Genet 1999; 65(3): 752–756. 12,13 VII as seen in Mobius syndrome). 10 Rojas-Martinez A, Garcia-Cruz D, Rodriguez Garcia A, Sanchez-Corona J, Rivas F. We present a unique variation of this combined syndrome and Poland-Moebius syndrome in a boy and Poland syndrome in his mother. Clin Genet which lends support to its broad spectrum of manifestation. The 1991; 40(3): 225–228. facial weakness in this patient is contralateral to the chest wall and 11 Pachajoa H, Isaza C. First case of Moebius-Poland syndrome in child prenatally exposed to misoprostol. Neurologia 2011; 26(8): 502–503. lower-limb deformities. His other features have been documented 12 Bavinck JN, Weaver DD. Subclavian artery supply disruption sequence: hypothesis of a in literature and these include dextrocardia, micrognathia, vascular etiology for Poland, Klippel-Feil, and Mobius anomalies. Am J Med Genet swallowing difficulty and hypotonia.5,7,11 The presence of 1986; 23(4): 903–918. dextrocardia is an uncommon occurrence in this combined 13 St Charles S, DiMario Jr FJ, Grunnet ML. Mobius sequence: further in vivo support for the syndrome with only two other cases reported.5,6 Majority of the subclavian artery supply disruption sequence. Am J Med Genet 1993; 47(2): 289–293. 14 Baraitser M. Genetics of Mobius syndrome. J Med Genet 1977; 14(6): 415–417. Poland–Mobius syndrome reported had marked hand deformity. 15 Graziadio C, Lorenzen MB, Rosa RF, Pinto LL, Zen PR, Travi GM et al. New report of a In contrast, this patient’s left arm and hand appears slightly familial case of Moebius syndrome presenting skeletal findings. Am J Med Genet A hypoplastic, only when compared with the right, and this has been 2010; 152A(8): 2134–2138.

Journal of Perinatology