Oral Manifestations of Noonan Syndrome: Review of the Literature and a Report of Four Cases

Rom J Morphol Embryol 2014, 55(4):1503–1509 R J M E ASE EPORTS Romanian Journal of C R Morphology & Embryology http://www.rjme.ro/ Oral manifestations of Noonan syndrome: review of the literature and a report of four cases SREEKANTH KUMAR MALLINENI1), CYNTHIA KAR YUNG YIU2), NIGEL MARTYN KING3) 1)Pediatric Dentistry, Vasan Dental care, Hyderabad, AP, India 2)Pediatric Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China 3)Winthrop Professor of Dentistry, School of Dentistry, The University of Western Australia, Perth, Australia Abstract Noonan syndrome (NS) was described by Noonan and Ehmke as a multi-system disorder, which is typically evident at birth. The incidence of this syndrome is estimated to be one per 2500 to one per 1000 and affects both genders. While the clinical manifestations of NS have been well documented, the oral manifestations have not been extensively discussed. The purpose of the present article is to (a) review the oral manifestations of NS reported in the literature, and (b) describe four cases (three females and one male) of NS, who presented with short stature, cardiac problems and various oral findings. Based on these cases, we conclude that many oral anomalies may have possible relationships with NS, which require multidisciplinary treatment planning and timely management. The importance of oral findings in NS has largely gone unnoticed and it is essential to consider oral manifestations as scoring criteria in the diagnosis of NS. Keywords: oral manifestations, Noonan syndrome, southern Chinese. Introduction during the early years of life of children with NS. Earlier reports demonstrated the long-term benefits of this Noonan syndrome (NS) [http://omim.org/entry/163950] treatment protocol [12]. Noonan syndrome patients with is an autosomal dominant disorder with an estimated a mutation in the PTPN11 gene usually respond less incidence of between one in 1000 and one in 2500 live effectively to growth hormone than those without the births [1]. The characteristic findings of this syndrome PTPN11 mutation [13]. include short stature, distinctive facial features, chest Frequently, the diagnosis of NS is based on facial and deformity, and congenital heart disease [2]. These findings musculoskeletal features. In infancy, the facial appearance were original reported by Kobylinski [3], and first docu- is characteristic and becomes more subtle towards middle mented by Noonan and Ehmke [4] as a unique entity with childhood and adulthood [14]. Infants with NS usually unusual facies and multiple malformations, and congenital presents with a small face which appears to be tucked heart defects. Subsequently, Noonan [5] described atypical beneath a large cranium, the head is large with narrowing facies, congenital heart disease, and clinical features of at the temples, these features result in a tall forehead. There Turner syndrome with normal chromosomes in 19 cases is hypotelorism and the nose is short; while the ears are (12 males and seven females). These two articles caused low-set, posteriorly rotated and an oval in shape. The neck puzzlement over the terminology surrounding an individual is also short with a low posterior hairline. Towards late with a phenotype of Turner syndrome. Meanwhile, Ford childhood, the expressionless facial appearance resembles et al. [6] had identified the karyotype 45X in a patient that of a myopathic face. In adolescence, the face is more with the diagnosis of Turner syndrome. Consequently, a triangular with a wide forehead, and pointed chin. The clear division was subsequently made between Turner eyes are less prominent but have sharp features. The neck is syndrome (45X, female only) and NS. The substantial longer than normal, and skin webbing or trapezius muscle differences between the two syndromes are now well prominence (webbed neck) are characteristic features documented. Although the basic features of NS resemble of NS. Also, the nipples are wide-spaced and low-set. those of Turner syndrome, the latter syndrome only affects Rounded shoulders and hyperextensibility are common females. Subsequently, “male Turner syndrome” was the features in subjects with NS [15]. Scoliosis has been term used to describe NS. Noonan syndrome also became reported in 10% to 15% of NS patients [16]. There are known as “pseudo-Ullrich Turner syndrome”, “Turner like several disorders with significant phenotypic overlaps with syndrome more details”, “female pseudo-Turner syndrome” NS; such as Turner syndrome, cardiofaciocutaneous (CFC) and “webbed neck syndrome”. syndrome, Costello syndrome, Leopard syndrome, Aarskog Noonan syndrome frequently presents with an auto- syndrome and Baraitser–Winter syndrome [2]; because of somal dominant pattern of inheritance, with a high pro- the differences in treatment, the prognosis, and recurrence portion of maternal transmission [7–9]. It has been reported concerns, the accurate early diagnosis of NS is critical. that the PTPN11 mutations in sporadic NS patients are Noonan syndrome, which is characterized by ocular, primarily of paternal origin [10, 11]. Pharmacological facial, cardiac, and oral anomalies, is association with short doses of growth hormone can be used to hasten growth stature. It has been suggested that early diagnosis of NS is ISSN (print) 1220–0522 ISSN (on-line) 2066–8279 1504 Sreekanth Kumar Mallineni et al. Cases Age important, because of its association with general and oral Authors Oral manifestations health [2]. However, the oral manifestations have never (gender) [years] High arch palate, micrognathic been extensively discussed in the literature. Therefore, the Okada et al. mandible, posterior cross bite, 1 (M) 8.1 purpose of this article was to review the oral manifestations [28] anterior open-bite, early of the Noonan syndrome and to present a report of the exfoliation of canines Yazdizadeh Neurofibromatosis and central oral manifestations in four southern Chinese subjects. 1 (M) 22 et al. [29] giant cell granuloma Edwards et al. Bilaterally occurring central 1 (F) 8 Review of the literature [30] giant cell lesions High arch palate, anterior Materials and Methods Asokan et al. Case 1 open bite, hypoplastic jaws, 13 [31] (F) retrognathic maxilla, A narrative review was performed on the oral mani- prognathic mandible festations of NS. This review differs from a systematic Cancino et al. Multiple giant cell lesions in 1 (F) 14 review by involving a general discussion of the subject, [32] the mandible Sharma et al. Malocclusion, crowding, whilst not having a stated hypothesis. An extensive search 1 (F) 9 of the reported literature, published between January 1966 [33] marginal gingivitis Malocclusion, labial hypotonia, and May 2012 was conducted using the MEDLINE, gingival inflammation, Case 1 Embase, and PubMed databases. The key words used in 14 retrognathic maxilla and (M) the search strategy were “oral manifestations”, “dental mandible, proclined incisors manifestations”, and “Noonan syndrome” in various Ortega Ade in maxilla and mandible et al. [34] Malocclusion, gingival combinations. The citation lists from the identified refe- inflammation, supernumerary Case 2 rences were subsequently examined and a hand search 13 teeth, prognathic maxilla and (M) was also performed in an attempt to identify additional mandible, retroclined reports. mandibular incisors Gingival enlargement, Results crowding associated with midline diastema, Sahebjamee 1 (F) 19 malocclusion, anterior cross- The literature search yielded case reports and a few et al. [35] case studies that reported the oral manifestations of NS. bite, taurodontism, impacted teeth, idiopathic The common oral manifestations included micrognathia, osteosclerosis, hypodontia high arch palate, malocclusion, impacted teeth, retroclined Malocclusion, hypodontia, mandibular incisors and giant cells in the jaws. The case high arch palate, impacted teeth deep-bite, retroclined reports and studies of the oral manifestations present in Emral and 1 (F) 13.3 mandibular incisors, Akcam [36] patients with NS are summarized in Table 1 [17–39]. asymmetry of tooth Table 1 – Published reports on the oral manifestations morphology of maxillary first of Noonan syndrome molars Ierardo et al. Malocclusion, deep bite, Cases Age 1 (F) 8 Authors Oral manifestations [37] ectopic eruption, hypodontia (gender) [years] Bufalino et al. Baird and Anomalous upper lateral 1 (M) 8 Giant cell lesions 7 - [38] De Jong [17] incisors Severe gingivitis and Nelson et al. Exanthemas eyes high arch supernumerary teeth, bilateral 1 (F) 6 Toureno and [18] palate 1 (M) 14.8 enlargement of the mental Chuong et al. Central giant cell lesions of Park [39] 2 of 17 - foramens and inferior-alveolar [19] jaw canals Case 1 5.1 (M) M: Male; F: Female. Case 2 13.1 Baird and De Jong [17] were the first to document Dunlap et al. (M) Cherubism [20] Case 3 seven cases spanning three generations with anomalous 6.9 (M) maxillary lateral incisors. Chuong et al. [19] subsequently Case 4 8 reported central giant cell lesions the jaws of two out of 17 (M) patients with NS; while Cohen and Gorlin [21] reported Cohen and Giant cell lesions of bones, 14 - Gorlin [21] and/or soft tissues 14 cases with similar findings. The association of peri- Torres-Carmona odontitis with NS was addressed in two patients reported by 2 (F) - Periodontitis et al. [22] Torres-Carmona et al. [22]. Subsequently, several authors Anterior open bite, prognathic Sugar et al. [23] 1 (M) 22 have discussed a number of oral manifestations such

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