|Year : 2016 | Volume
| Issue : 2 | Page : 207-210
Noonan Syndrome with cleft palate: A rare case report
Munish Kumar, Vinod Vijay Chandar, Sridevi Koduri, Shailaja Sankireddy
Department of Oral Medicine and Radiology, SGT Dental College, Gurgaon, Haryana, India
|Date of Submission||01-Jun-2015|
|Date of Acceptance||21-Nov-2016|
|Date of Web Publication||02-Dec-2016|
Department of Oral Medicine and Radiology, SGT Dental College, Gurgaon - 122 505, Haryana
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Noonan syndrome is a clinically and genetically heterogeneous condition characterized by distinctive facial features, short stature, chest deformity, congenital heart diseases and other comorbidities. It is an autosomal dominant disorder with complete penetrance but variable expressivity. Until recently, diagnosis was based solely on clinical findings, however, genetic mutations responsible for Noonan syndrome, PTPN11 was identified on chromosome number 12 resulting in a gain of function of the nonreceptor protein tyrosine phosphatase SHP-2 protein in 61% of the patients with an estimated prevalence of 1 in 1000 to 1 in 2500 live births, which appears to be consistent worldwide. There are also evidences of autosomal recessive forms of Noonan syndrome. This is a case report of Noonan syndrome with a rare presentation of soft tissue cleft palate.
Keywords: Cleft palate, Noonan syndrome, short stature, webbing of neck
|How to cite this article:|
Kumar M, Chandar VV, Koduri S, Sankireddy S. Noonan Syndrome with cleft palate: A rare case report. J Indian Acad Oral Med Radiol 2016;28:207-10
|How to cite this URL:|
Kumar M, Chandar VV, Koduri S, Sankireddy S. Noonan Syndrome with cleft palate: A rare case report. J Indian Acad Oral Med Radiol [serial online] 2016 [cited 2019 Dec 14];28:207-10. Available from: http://www.jiaomr.in/text.asp?2016/28/2/207/195141
| Introduction|| |
In 1962, Jacqueline Noonan, a pediatric cardiologist, identified 9 patients whose faces were remarkably similar and who, in addition, had short stature, significant chest deformities and pulmonary stenosis. In 1968, Dr. Noonan published a case series with these 9 patients along with an additional 10 patients.  The eponym "Noonan syndrome" was adopted in recognition of Dr. Noonan because she was the first to indicate that this condition occurred in both genders, was associated with normal chromosomes, included congenital heart defects and could be familial. The term Noonan syndrome has been applied to phenotypic males and females who have certain anomalies that occur also in females with Turner syndrome.  Various oral manifestations have been suggested in the literature, however, Noonan's syndrome with cleft palate has not been reported till now. Here, we are presenting a case of Noonan syndrome with cleft palate.
| Case History|| |
A boy aged 10 years born to non-consanguineous marriage reported to the Department of Oral Medicine and Radiology for routine check-up as a part of a school health program. Patient was fully examined extraorally and intraorally with reference from a pediatrician available in the hospital unit revealing the following clinical features.
On physical examination, the child was conscious, cooperative, and well-oriented to time, place, and person. He had no sign of pallor, icterus, cyanosis, lymphadenopathy, clubbing, splinter hemorrhage, osler nodes and pedal edema. At the time of examination, the patient's body temperature was 37°C with a pulse rate of 100 beats/min, with good volume, which was regular and synchronous. Respiratory rate was 28 cycles/min and blood pressure was 100/70 mmHg. Patient was of short stature with a height of 132 cm, which appears to be less compared to same age group individuals [Figure 1]. Chest examination revealed deformed sternum and characteristic pectus deformity with winged scapula and rounded shoulders. In addition, nipples were wide-spaced and appeared to be low-set. On genital examination, testicles appeared to be small.
Extraoral examination revealed asymmetric head with high frontal hairline [Figure 2] and low back hairline [Figure 3], which is a characteristic feature of Noonan's syndrome. , Flat nasal bridge with columella of nose appeared to be deficient. Webbing of neck, which is also a characteristic feature, , was seen on the right side which caused the patient's habit to keep his head tilted toward the right side; in addition, patient's face appeared to be deviated on the right side. His eyes had prominent epicanthal folds and ears appeared to be low set. Lips were incompetent.
Intraoral examination revealed anterior open bite [Figure 4] with infraoccluded maxillary incisors causing increased overjet and overbite. Dentition examination revealed mal-alignment with palatally displaced 52 and crossbite with respect to 62 and 33. 85 was absent clinically and root stumps of 55, 64, and 65 were present. Patient had high arched palate with a cleft present at the junction of hard and soft palate classified according to the Veau classification as incomplete type II [Figure 5].
Orthopantomogram [Figure 6] revealed normal growth pattern and eruption sequence of teeth and tooth buds, as confined to the age of the patient. Tooth 85 was not present and root stumps of 55, 64, and 65 were appreciated. Radiopaque occlusion restorations were noticed in 54 and 84, and proximal dental caries was seen in relation to 74. Condyles appeared to be normal with no sign of ankylosis. Lateral cephalogram view revealed midfacial hypoplasia and anterior open bite with infraoccluded maxillary incisors [Figure 7] whereas posterioranterior (PA) view revealed skeletal asymmetry and night bulb appearance of the skull was appreciated [Figure 8]. Multidisciplinary approach treatment, i.e., orthodontic and prosthodontic treatment, was planned for the patient.
There are several disorders with significant phenotypic overlap with Noonan syndrome, such as Turner syndrome, having cardiac features typically left-sided compared to right-sided in Noonan syndrome. Cardiofaciocutaneous (CFC) syndrome and Costello syndrome are often confused for Noonan syndrome, particularly in the newborn period, however, with CFC syndrome, coarser facial features, severe feeding problems, follicular hyperkeratosis, sparse eyebrows and eyelashes are prominent. Other disorders with significant phenotypic overlap with Noonan syndrome include neurofibromatosis type 1 having multiple café au lait, axillary, and inguinal freckling, cutaneous neurofibroma, and iris Lisch nodules, which are not seen in Noonan syndrome as well as lentigines, electrocardiographic anomalies, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, and deafness (LEOPARD) syndrome. 
| Discussion|| |
Noonan syndrome is an autosomal dominant condition. It resembles Turner syndrome phenotypically, however, patients have apparently normal sex chromatin. The specific cause for Noonan syndrome is not known. Both sporadic and autosomal dominant cases have been identified. A gene for Noonan Syndrome NS-1 is located in the 12q 22-region, but there is genetic heterogeneity. These patients have delayed pubertal development but no primary gonadal failure. The most common abnormalities in Noonan syndrome are short stature, webbing of the neck, pectus carinatum or pectus excavatum, cubitus valgus, hypertelorism, downward slanted palpebral fissures, ptosis, micrognathia, and ear abnormalities. Moderate mental retardation and high frequency sensorineural deafness can be present. Approximately 50% of these individuals have congenital heart disease. 
All individuals with Noonan syndrome require detailed and regular follow-up for ongoing developmental, audiologic, ophthalmologic, cardiac, neurologic and other associated problems. The high frequency of these abovementioned abnormalities associated with Noonan syndrome emphasizes the need for early diagnosis. Early diagnosis of this relatively common condition would result in better use of diagnostic and therapeutic approaches. The present report describes a narrow high-arched palate and an open bite with accompanying Noonan syndrome. There have been several other reports of oral findings with this syndrome, however, few have reported a narrow high-arched palate with an open bite.  A deeply grooved philtrum and poor tongue control may present difficulties when treating open bite. 
In contrast, the width of the dental arch was markedly narrow at both the maxilla and mandibular landmarks. Early closure of cranial sutures may influence the growth of the dental arch. The present case exhibited hypertelorism, ptosis, a divergent squint and a tendency for exophthalmos. Noonan  reported that deformity of the sternum with an early closure of sutures was a frequently seen feature and hand-wrist radiograph can be useful for determination of growth stage as the pubertal growth spurt might be reduced or delayed. Joint laxity is present in more than half of the patients and talipes equinovarus, radioulnar synostosis, cervical spine fusion and joint contractures are less common causing temporomandibular joint and muscular pain. ,
Several hemolytic diseases such as low clotting factors XI and XII, acute lymphoblastic leukemia and chronic myelomonocytic leukemia have been described in patients with Noonan syndrome. Because bleeding anomalies and blood clotting disorders have been reported, a full hematologic workup must be performed before any dental surgery. , More than half of the male patients have undescended testes. Female patients have normal pubertal development and fertility. Fertility in males with undescended testes may be decreased. For this reason, the mother is more frequently the transmitting parent in familial cases.  Karyotyping may be necessary if full phenotypic expression is not apparent. Human growth hormones have resulted in improvement in growth velocity comparable to that seen in patients with Turner syndrome without adverse effects. 
| Conclusion|| |
No confirmatory or diagnostic testing for Noonan Syndrome is available. This entity remains a strictly clinical diagnosis because of characteristic dental and skeletal structures and dentists can play a major role in the diagnosis of this syndrome.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Noonan JA. Hypertelorism with Turner phenotype. A new syndrome with associated congenital heart disease. Am J Dis Child 1968;116:373-80.
Nora JJ, Nora AH, Sinha AK, Spangler RD, Lubs HA. The Ullrich-Noonan syndrome (Turner phenotype). Am J Dis Child 1974;127:48-55.
Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME, et al. Noonan Syndrome: Clinical Features, Diagnosis, and Management Guidelines. Pediatrics 2010;126:746-59.
van der Burgt I. Noonan syndrome. Orphanet J Rare Dis 2007;2:4.
Tartaglia M, Gelb BD, Zenker M. Noonan syndrome and clinically related disorders. Best Pract Res Clin Endocrinol Metab 2011;25:161-79.
Okada M, Sasaki N, Kaihara Y, Okada R, Amano H, Miura K, et al. Oral findings in Noonan syndrome: Report of a case. J Oral Sci 2003;45:117-21.
Emral ME, Akcam MO. Noonan syndrome: A case report. J Oral Sci 2009;51:301-6.
Marino B, Diglio MC, Toscano A, Giannotti A, Dallapiccola B. Congenital heart diseases in children with Noonan syndrome: An expanded cardiac spectrum with high prevalence of atrioventricular canal. J Pediatr 1999;135:703-6.
Asokan S, Muthu MS, Prabhu VR. Noonan syndrome: A case report. J Indian Soc Pedod Prevent Dent 2007;9:144-7.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]