Journal of Indian Society of Pedodontics and Preventive Dentistry
Journal of Indian Society of Pedodontics and Preventive Dentistry
                                                   Official journal of the Indian Society of Pedodontics and Preventive Dentistry                           
Year : 2015  |  Volume : 33  |  Issue : 1  |  Page : 57--60

LEOPARD syndrome: You could be the first one to diagnose!


Pallavi Urs1, Sapna Konde2, Nidhi Chouta3, Sunil Raj2,  
1 Department of Pedodontics and Preventive Dentistry, Krishnadevaraya College of Dental Sciences and Hospital, Bangalore, Karnataka, India
2 Department of Pedodontics and Preventive Dentistry, A.E.C.S Maaruti College of Dental Science and Research Centre, Bangalore, Karnataka, India
3 Department of Oral Medicine and Radiology, Bangalore Institute of Dental Sciences and Post Graduate Research Centre, Bangalore, Karnataka, India

Correspondence Address:
Dr. Pallavi Urs
Department of Pedodontics and Preventive Dentistry, Krishnadevarya College of Dental Science and Hospital, Bangalore 57, Karnataka
India

Abstract

Leopard syndrome is a rare genetic disease complex associated with multiple anomalies. The main anomalies are summarized in the acronym LEOPARD in which each letter corresponds to mnemonic for the major features of this disorder:multiple Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensory neural Deafness. A Four year old male patient reported with the chief complaint of decayed anterior tooth without any relevant past medical history. Based on the clinical features; the child was subjected to genetic and general physical appraisal which helped in identifying Leopard syndrome. A multidisciplinary approach by the pedodontist and medical consultants aided in the identification and management of this rare syndrome. LEOPARD syndrome has been rarely reported in the diseases associated with oro-dental or craniofacial anomalies. In this case report we describe these anomalies and discuss the relationship between them and the proposed etiology of the disease.



How to cite this article:
Urs P, Konde S, Chouta N, Raj S. LEOPARD syndrome: You could be the first one to diagnose!.J Indian Soc Pedod Prev Dent 2015;33:57-60


How to cite this URL:
Urs P, Konde S, Chouta N, Raj S. LEOPARD syndrome: You could be the first one to diagnose!. J Indian Soc Pedod Prev Dent [serial online] 2015 [cited 2022 May 25 ];33:57-60
Available from: https://www.jisppd.com/text.asp?2015/33/1/57/149008


Full Text

 Introduction



LEOPARD syndrome (OMIM ID no. 151100) is a rare genetically heterogeneous disorder caused by mutations in the PTPN11 gene on chromosome 12q24; about 200 patients have been reported worldwide. PTPN11: Protein tyrosine phosphatase, nonreceptor type 11 is a protein coding gene. It is a member of the protein tyrosine phosphatase family known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle and oncogenic transformation.

Within the group of the so called "neuro-cardio-facial-cutaneous" syndromes, LEOPARD syndrome is probably the second most common disorder after Noonan syndrome. However, LEOPARD syndrome is likely under diagnosed as many of its features are mild and the correct diagnosis might be missed in the absence of lentiginosis. [1]

Multiple lentigines syndrome was first reported by Zeisler in 1936, a few decades later, Gorlin et al. reviewed this disorder and coined the LEOPARD acronym supporting the concept of generalized condition which was inherited as an Autosomal dominant trait. LEOPARD is based on an acronym, mnemonic for the major features of this disorder: Multiple Lentigines, electrocardiographic (ECG) conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensor neural Deafness.

LEOPARD syndrome has been rarely reported in the diseases associated with oro-dental or craniofacial anomalies. In this case report we describe these anomalies and discuss the relationship between them and the proposed etiology of the disease.

 Clinical Presentation



A 4-year-old male patient reported, with the chief complaint of decayed upper anterior tooth. The history revealed caries was noticed 3 months ago. Feeding habits revealed the child has been breast fed for the past 4 years. No other relevant medical history was mentioned.

General examination revealed multiple lentigines over face, trunk, and hands. Ocular hypertelorism with a wide nasal bridge and thick averted lips were noticeable [Figure 1] and [Figure 2]. Intraoral examination revealed primary dentition, dental caries in relation to primary maxillary central incisor, missing primary mandibular left lateral incisor, high arch palate with increased overjet [Figure 3] and [Figure 4]. After recording the above features the patient was referred to the clinical geneticist and pediatrician for further appraisal.{Figure 1}{Figure 2}{Figure 3}{Figure 4}

The genetic, clinical, pathological and radiographic investigations were performed. The genetic appraisal which included the DNA mutation screening and linkage analysis of the PTPN11 confirmed germ line mutations in the PTPN11 gene. The thyroid profile showed hypothyroidism. Mild asymmetrical septal hypertrophy was noticed after thorough cardiac evaluation. Ocular hypertelorism with myopia and low audibility was confirmed.

The biopsy of the lentigo revealed an increased number of melanocytes per unit skin area and prominent rete ridges. Electron microscopic examination revealed large accumulations of melanosomes within the Langerhans cells orthopantamogram (OPG) [Figure 5] showed missing primary mandibular left lateral incisor and all the four second premolar tooth buds. Intraoral periapical radiograph in relation to the upper anteriors revealed deep dental caries in relation to the maxillary central incisors.{Figure 5}

Based on the overall clinical examination and the findings of various diagnostic investigations a confirmatory diagnosis of LEOPARD syndrome was established.

Treatment

After obtaining the consent from the pediatrician, antibiotic prophylaxis was initiated prior to the pulpectomy procedure in relation to primary maxillary right central incisor. Postobturation with calcium hydroxide and iodoform (metapex), Omega spring was placed in relation to primary maxillary right central incisor and core build up was done with composite resin. Primary maxillary left central incisor was restored with Strip crown [Figure 6] and [Figure 7]. In addition to the treatment the parents were counseled with respect to the diet and oral hygiene and the child was weaned off breast feed. A multi-disciplinary approach and follow-up with pediatric and medical consultants is being done for the general well-being of the patient.{Figure 6}{Figure 7}

 Discussion



Molecular studies have proven that LEOPARD syndrome is caused by mutations in PTPN11, a gene encoding the protein tyrosine phosphatase SHP-2 located at band 12q24.1. [2] Based on clinical analysis of a large series of patients in 1976 Voron et al. proposed minimum criteria for the diagnosis of LEOPARD. [3]

Multiple lentigines must be present.

Features of at least two other categories must be present.

Cardiac structural or ECG abnormalitiesGenitourinary abnormalitiesEndocrine abnormalitiesNeurologic defectsCephalofacial dysmorphismShortness of statureSkeletal abnormalitiesOther cutaneous abnormalities.If lentigines are absent, a diagnosis of LEOPARD syndrome may be established if the patient has features in at least three above-mentioned categories and has an immediate relative with the defined diagnosis.

About 35% of the LEOPARD syndrome patients demonstrate various cephalofacial findings. Ocular hypertelorism was the most frequently reported (25%). Other findings include the following: Mandibular prognathism. Broad nasal root, dysmorphic skull, low-set ears, dental abnormalities, high palate arch, epicanthal folds, ptosis and corneal tumors. [4]

It has been suggested that LEOPARD syndrome results from an anomaly of neural crest elements which give origin to pigmented cells of the epidermis, portions of the sympathetic nervous system including chromaffin cells of the adrenal medulla and of the gut, myenteric plexus and Schwann cells. The neural crest cells also contribute to the formation of the dental papillae and otic vesicles. Therefore it is likely that most of the abnormalities found may be explained by a derangement of these elements. [5]

If LEOPARD syndrome is the result of a neural crest anomaly (Ho et al., 1989), then all organs originating from the neural crests will be affected. This would provide a link between the disease and the dental and craniofacial anomalies. [6]

The dental tissues develop from neural crest cells which also participate in the formation of some craniofacial bones (Couly, 1995). The observed dental anomalies could be explained by a retardation or lack of migration of the neuralcrest cells (Benoit et al., 1979).

The present case reported to the department with only history of dental caries and no existing relevant medical history. Early diagnosis was established by the presence of lentigines, Ocular hypertelorism with a wide nasal bridge and thick averted lips. Final diagnosis was made when mild asymmetrical septal hypertrophy, endocrine abnormalities, that is, hypothyroidism, Ocular hypertelorism with myopia and low audibility was detected, which were pathognomic of the syndrome. In addition to these clinical findings, dental anomalies, that is, the primary mandibular lateral incisor and permanent teeth; all four second premolars agenesis also confirmed the diagnosis.

The oral findings in our case required early pulp therapy with aesthetic restorations. Precautions were taken during pulpectomy procedure, under antibiotic prophylaxis and premedication, to prevent infective endocarditis. Following pulp therapy esthetic restorations was performed by using omega posts and strip crowns. [7] Early diagnosis of the syndrome in the present case has helped the child in receiving appropriate treatment and leading a normal lifestyle.

 Conclusion



The present case report emphasizes the early diagnosis of a rare condition called leopard syndrome that is not usually encountered by the dental fraternity. As the dental anomalies and other general anomalies of LEOPARD syndrome are associated with neural crest cells, we propose that dental and craniofacial anomalies be added to the D of the Gorlin's acronym, LEOPARD.

Greater awareness of the possibility of dental and craniofacial anomalies is important in the diagnosis and management of these patients. As the patient is still in the primary dentition stage further recall and maintenance with both preventive and interceptive measures is been carried out for the wellbeing of the child. The case also illustrates the necessity of a multi-disciplinary approach between pediatricians and dentists for better management and follow-up of individuals with LEOPARD syndrome.

Why this paper is important to pediatric dentists

Lack of migration of the neural crest cells can be the cause of tooth agenesis in leopard syndromeDental anomalies can be added to the D of Leopard syndromeSometimes the clinical diagnosis of Leopard syndrome can be unnoticed, the pediatric dentist can aid in the diagnostic process.

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