|Year : 2020 | Volume
| Issue : 1 | Page : 59-63
Dental phenotype of multiple impacted supernumerary teeth in Wiedemann–Steiner syndrome
Priyanka Verma1, Seema Kapoor2, Haseena Sait2, Sujoy Ghosh1, Sunita Gupta1
1 Department of Oral Medicine and Radiology, Maulana Azad Institute of Dental Sciences, New Delhi, India
2 Department of Paediatrics, Maulana Azad Medical College, New Delhi, India
|Date of Submission||29-May-2019|
|Date of Acceptance||20-Aug-2019|
|Date of Web Publication||20-Jan-2020|
Dr. Sunita Gupta
Department of Oral Medicine and Radiology, Maulana Azad Institute of Dental Sciences, Bahadur Shah Zafar Marg, New Delhi - 110 002
Source of Support: None, Conflict of Interest: None
Wiedemann–Steiner syndrome (WSS) is a rare autosomal dominant disorder characterized by short stature, intellectual disability, developmental delay, hypertrichosis cubiti, and dysmorphic facial features (thick eyebrows with a lateral flare, long eyelashes, vertically narrow and downslanting palpebral fissures, and wide nasal bridge). Dental findings reported with this syndrome are premature eruption of dentition, malocclusion, hypodontia, cleft palate, and retrognathia. We report a 12-year-old boy with a heterozygous two-base pair deletion in exon 22 of the KMT2A gene, resulting in a frameshift and premature truncation of the protein 17 amino acids downstream to codon 1974. Our patient exhibited multiple impacted supernumerary teeth which have never been reported earlier. This extends the dental phenotypic spectrum of WSS. To the best of our knowledge, this is the first reported case from India.
Keywords: Hypertrichosis cubiti, KMT2A gene, multiple impacted supernumerary teeth, Wiedemann–Steiner syndrome
|How to cite this article:|
Verma P, Kapoor S, Sait H, Ghosh S, Gupta S. Dental phenotype of multiple impacted supernumerary teeth in Wiedemann–Steiner syndrome. J Cleft Lip Palate Craniofac Anomal 2020;7:59-63
|How to cite this URL:|
Verma P, Kapoor S, Sait H, Ghosh S, Gupta S. Dental phenotype of multiple impacted supernumerary teeth in Wiedemann–Steiner syndrome. J Cleft Lip Palate Craniofac Anomal [serial online] 2020 [cited 2020 Apr 10];7:59-63. Available from: http://www.jclpca.org/text.asp?2020/7/1/59/276191
| Introduction|| |
Wiedemann–Steiner syndrome (WSS) (OMIM 605130) is a rare autosomal dominant disorder which was first described by Wiedemann in 1989 and later by Steiner in 2000., The characteristic facial features include thick or arched eyebrows with a lateral flare, long eyelashes, vertically narrow and downslanting palpebral fissures, wide nasal bridge with dental anomalies in the form of premature eruption of dentition, malocclusion, hypodontia, cleft palate, and retrognathia., Short stature, intellectual disability with behavioral abnormalities, and hypertrichosis cubiti (hairy elbow) are among other distinctive features which are reported in this syndrome. Heterozygous mutations in KMT2A gene (OMIM 159555) which encodes a transcriptional coactivator, lysine methyltransferase 2A, which in turn catalyzes histone H3 lysine 4 methylation through the SET domain is present in the Drosophila Trithorax protein and was subsequently identified in the Drosophila Su3-9 and 'Enhancer of zeste' proteins, from which the acronym SET is derived [Su3-9, Enhancer-of-zeste and Trithorax. Here, we report a male patient who had unusual dental finding that was not previously reported.
| Case Report|| |
A 12-year-old boy reported to us with the primary concern of malaligned teeth. The patient was first born from third-degree consanguineous marriage. Antenatally, his mother was diagnosed with hypothyroidism in the first trimester and was on levothyroxine therapy. The child was born full term through elective cesarean delivery due to fetal distress. His birth weight was 1800 g and was ventilated for a period of 4 days due to perinatal asphyxia. Diffuse hypertrichosis was noted all over the body at the time of birth. He was also operated for the left inguinal hernia at 1½ years of age.
Subsequently, the patient suffered recurrent ear and upper respiratory tract infections, and his mother noticed poor physical growth, delay in attainment of milestones in all developmental domains, poor scholastic performance, and aggressive behavior at school for which medical attention was sought.
On evaluation, his weight was 28 kg (1.60 standard deviation [SD]), height was 118 cm (4.15 SD), and body mass index was 20 kg/m2( 0.64 SD), indicating severe stunting. According to the Stanford–Binet Intelligence Scale, mental assessment performed at 7 years of age revealed mental age of 5.08 years with an intelligence quotient of 71 (borderline). A perusal of cognitive profile indicated relative cognitive strengths in simple comprehension and concrete vocabulary, number concept, and simple fine motor tasks and limitations in the areas of expressive language, verbal reasoning, auditory memory, and visual motor tasks. General physical examination revealed pectus excavatum, marked hirsutism, bushy eyebrows, long eyelashes, hypertelorism, narrow downslanted palpebral fissures [Figure 1], broad nasal bridge, deviated nasal septum, low-set ears, and microretrognathia. Characteristic findings included hypertrichosis cubiti (hairy elbows) [Figure 2] along with fleshy hands, and feet brachydactyly and radial deviation of the right index finger were also noted. Intraorally, high-arched palate, narrow alveolar arches, and malaligned teeth were seen [Figure 3] and [Figure 4].
|Figure 1: Characteristic facial features include thick hairy eyebrows, long eyelashes, hypertelorism, downslanted and narrow palpebral fissures, deviated nasal septum, broad nasal bridge, lowset ears and pectus excavatum|
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|Figure 2: GCharacteristic hypertrichosis (hypertrichosis cubiti) noted on the arm|
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|Figure 3: Labially placed maxillary canines and right upper first premolar with palatally placed both the maxillary lateral incisors. The upper right maxillary deciduous canine is retained, and a supernumerary tooth is seen between central incisor and deciduous canine suggestive of malocclusion|
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|Figure 4: Labially placed maxillary canines and right upper first premolar with palatally placed both the maxillary lateral incisors|
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Orthopantomogram [Figure 5] revealed multiple impacted teeth/teeth-like structures in all the four quadrants in premolar–molar regions, which were further confirmed on cone-beam computed tomography scan as multiple impacted teeth in all the quadrants of the jaws in different stages of maturation [Figure 6] and [Figure 7].
|Figure 5: Orthopantomogram reveals multiple impacted supernumerary teeth/teeth-like structures in all the quadrants of jaws. Teeth show resemblance to premolars on the left side of mandible and no resemblance to any teeth on the right side of mandible|
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|Figure 6: Axial section of conebeam computed tomography shows lingually placed impacted (incompletely formed) supernumerary teeth bilaterally in the mandible|
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|Figure 7: Coronal section of conebeam computed tomography show palatally/lingually placed impacted supernumerary teeth bilaterally in the maxilla and mandible|
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Endocrine evaluation unveiled normal prolactin and gonadotrophic and thyroid function tests. Growth hormone provocative tests with two agents (clonidine and insulin) confirmed the growth hormone deficiency. Immunoglobulin (Ig) profile revealed hyper-IgE (344.2 IU/mL) and decreased IgG (13.77 mg/dL) with normal IgA (4.06 gm/L) and IgM (0.82 gm/L) levels. Skeletal surveys, ECHO, and abdominal ultrasound examination were normal.
Genomic DNA was extracted from peripheral blood leukocytes of the patient. Targeted gene capture was performed using a custom capture kit. The libraries were sequenced to mean >80–100X coverage on illumina sequencing platform. The sequences obtained are aligned to human reference genome (Genome Reference Consortium h37/hg19) Burrows-Wheeler Aligner (BWA) is an efficient program that aligns relatively short nucleotide sequences against a long reference sequence and analyzed using Picard and Stands for Genome Analysis Toolkit. It is a software package used to analyse next-generation resequencing data. A heterozygous two-base pair deletion in exon 22 of the KMT2A gene was identified that resulted in a frameshift and premature truncation of the protein 17 amino acids downstream to codon 1974.
| Discussion|| |
We report a 12-year-old boy with moderate intellectual disability, severe stunting, marked hirsutism, immunodeficiency, and growth hormone deficiency. New finding included multiple impacted supernumerary teeth expanding the oral spectrum of the WSS.
Oral findings that have been previously described in this syndrome consisted of premature eruption of permanent teeth,, spacing of teeth, premature loss of primary dentition and hypodontia, high-arched palate, cleft palate, glossoptosis, and dental malposition. Few other findings described by various authors,, are tabulated in [Table 1]. Our patient, however, exhibited a new finding of multiple impacted supernumerary teeth.
Predisposition to frequent urinary tract infections,, periodic respiratory infections, and recurrent otitis media have previously been reported in patients with KMT2A mutations, which supports the view of compromised immunological function in these patients. Stellacci et al. proposed a possible genotype–phenotype correlation for KMT2A mutations. They reported a boy with congenital immunodeficiency with low levels of Igs and severe epilepsy and a de novo missense mutation c.3481T >G (p. Cys1161Gly). They proposed that missense mutations affect few functional domains, which, in turn, have an impact on the transcriptional control of genes that are involved in the regulation of immune function disorder.
Bogaert et al. also reported combined variable immunodeficiency in a patient with WSS, which strengthened the unknown role for KMT2A in B-cell function. Although panhypogammaglobulinemia was reported in their study, our patient had an isolated IgG deficiency with frequent infections.
The child is being managed with titrated intravenous Ig infusion at desired intervals of time. Furthermore, the patient is being evaluated by different specialties as the treatment requires multidisciplinary approach.
No standard protocol for dental management is available in the literature. However, different opinions exist regarding the treatment of supernumerary teeth. Various factors which need to be taken into consideration of supernumerary teeth depend on the stage of the crown and root development, eruption/noneruption, distance from the adjacent teeth root, and malocclusion of teeth.,,
Extraction of the supernumerary teeth is advised where delayed, altered, and noneruption of the adjacent tooth is evident, interference of supernumerary tooth with active tooth movement during orthodontic treatment, associated pathology such as cyst formation. Surgical intervention is not required if supernumerary teeth are not causing any clinical adverse effect on adjacent teeth/surrounding structures and if no future orthodontic treatment is required.,
In the present case, orthodontic treatment is advised for the management of malaligned teeth. In addition, extraction of supernumerary teeth is recommended, as they may interfere with the active movement of teeth during the orthodontic treatment.
To conclude, our case extends the dental phenotypic spectrum of WSS. It is also recommended to perform immunodeficiency workup in these individuals as recurrent infections can significantly affect long-term health and life expectancy of these children as it is a treatable complication.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's parents have given their consent for patient's images and other clinical information to be reported in the journal. The patient's understand that the patient's name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Wiedemann HR, Grosse FR, Dibbern H. A syndrome of abnormal facies, short stature, and psychomotor retardation. Atlas of Clinician Syndromes: A Visual aid to Diagnosis for Clinicians and Practicing Physicians. 2nd
ed. London: Wolfe Publishing Ltd.; 1989. p. 198-9.
Steiner CE, Marques AP. Growth deficiency, mental retardation and unusual facies. Clin Dysmorphol 2000;9:155-6.
Jones WD, Dafou D, McEntagart M, Woollard WJ, Elmslie FV, Holder-Espinasse M, et al. De novo
mutations in MLL cause Wiedemann-Steiner syndrome. Am J Hum Genet 2012;91:358-64.
Nakamura T, Mori T, Tada S, Krajewski W, Rozovskaia T, Wassell R, et al.
ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol Cell 2002;10:1119-28.
Strom SP, Lozano R, Lee H, Dorrani N, Mann J, O'Lague PF, et al.De novo
variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing. BMC Med Genet 2014;15:49.
Mendelsohn BA, Pronold M, Long R, Smaoui N, Slavotinek AM. Advanced bone age in a girl with Wiedemann-Steiner syndrome and an exonic deletion in KMT2A (MLL). Am J Med Genet A 2014;164A: 2079-83.
Miyake N, Tsurusaki Y, Koshimizu E, Okamoto N, Kosho T, Brown NJ, et al.
Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations. Clin Genet 2016;89:115-9.
Li N, Wang Y, Yang Y, Wang P, Huang H, Xiong S, et al.
Description of the molecular and phenotypic spectrum of Wiedemann-Steiner syndrome in Chinese patients. Orphanet J Rare Dis 2018;13:178.
Baer S, Afenjar A, Smol T, Piton A, Gérard B, Alembik Y, et al.
Wiedemann-steiner syndrome as a major cause of syndromic intellectual disability: A study of 33 French cases. Clin Genet 2018;94:141-52.
Dunkerton S, Field M, Cho V, Bertram E, Whittle B, Groves A, et al.
A de novo mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome. Am J Med Genet A 2015;167A: 2182-7.
Sun Y, Hu G, Liu H, Zhang X, Huang Z, Yan H, et al.
Further delineation of the phenotype of truncating KMT2A mutations: The extended Wiedemann-Steiner syndrome. Am J Med Genet A 2017;173:510-4.
Enokizono T, Ohto T, Tanaka R, Tanaka M, Suzuki H, Sakai A, et al.
Preaxial polydactyly in an individual with Wiedemann-Steiner syndrome caused by a novel nonsense mutation in KMT2A. Am J Med Genet A 2017;173:2821-5.
Koenig R, Meinecke P, Kuechler A, Schäfer D, Müller D. Wiedemann-Steiner syndrome: Three further cases. Am J Med Genet A 2010;152A: 2372-5.
Stellacci E, Onesimo R, Bruselles A, Pizzi S, Battaglia D, Leoni C, et al.
Congenital immunodeficiency in an individual with Wiedemann-Steiner syndrome due to a novel missense mutation in KMT2A. Am J Med Genet A 2016;170:2389-93.
Bogaert DJ, Dullaers M, Kuehn HS, Leroy BP, Niemela JE, De Wilde H, et al.
Early-onset primary antibody deficiency resembling common variable immunodeficiency challenges the diagnosis of Wiedeman-Steiner and Roifman syndromes. Sci Rep 2017;7:3702.
Cakan DG, Ulkur F, Taner T. The genetic basis of dental anomalies and its relation to orthodontics. Eur J Dent 2013;7:S143-7. [Full text]
Toureno L, Park JH, Cederberg RA, Hwang EH, Shin JW. Identification of supernumerary teeth in 2D and 3D: Review of literature and a proposal. J Dent Educ 2013;77:43-50.
Koch H, Schwartz O, Klausen B. Indications for surgical removal of supernumerary teeth in the premaxilla. Int J Oral Maxillofac Surg 1986;15:273-81.
Munns D. A case of partial anodontia and supernumerary tooth present in the same jaw. Dent Pract Dent Rec 1967;18:34-7.
Rajab LD, Hamdan MA. Supernumerary teeth: Review of the literature and a survey of 152 cases. Int J Paediatr Dent 2002;12:244-54.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]