Aneta Witt-Porczyk1, Paula Piekoszewska-Ziętek2, Anna Turska-Szybka2, *Dorota Olczak-Kowalczyk2
Angelman syndrome – fenotype features and oral health status
Zespół Angelmana – cechy fenotypowe i stan zdrowia jamy ustnej
1Private practice, Warsaw, Poland
2Department of Pediatric Dentistry, Medical University of Warsaw, Poland
Head of Department: Professor Dorota Olczak-Kowalczyk, MD, PhD
Streszczenie
Wstęp. Zespół Angelmana jest rzadko występującą chorobą neurogenetyczną o niewyjaśnionej ostatecznie etiologii. Obraz kliniczny jest zróżnicowany w zależności od genotypu pacjenta.
Cel pracy. Celem pracy była prezentacja objawów zespołu Angelmana w obrębie twarzoczaszki oraz stanu higieny, dziąseł i uzębienia u dzieci z tym zespołem.
Materiał i metody. Przeprowadzono badanie zewnątrz- i wewnątrzustne pacjentów z zespołem Angelmana oraz ogólnie zdrowych, zwracając uwagę na obecność cech dysmorficznych, w tym kształtu i symetrii twarzy, stanu skóry i warg, stanu dziąseł i higieny, próchnicy zębów, zmian pochodzenia niepróchnicowego, nieprawidłowości wielkości, kształtu, liczby i ustawienia zębów w łuku zębowym. Uzyskane wyniki poddano analizie statystycznej.
Wyniki. U pacjentów z zespołem Angelmana obserwowano hipotonię mięśnia okrężnego ust, duży język oraz wady zgryzu. W grupie badanej odnotowano wyższe wartości wskaźnika higieny jamy ustnej niż w grupie kontrolnej (PLI, odpowiednio 1,42 ± 0,53 i 0,59 ± 0,38; p = 0,005). Wyższe były także wartości GI, jednak różnica nie była istotna statystycznie (GI odpowiednio 0,10 ± 0,18 i 0,00 ± 0,00; p = 0,147). Próchnica zębów występowała z podobną częstością, jej nasilenie było istotnie statystycznie większe w grupie z zespołem Angelmana.
Wnioski. Pacjenci z zespołem Angelmana wykazują cechy predysponujące do rozwoju chorób uzębienia. Konieczne jest zapewnienie stałej opieki stomatologicznej i intensyfikacja profilaktyki przeciwpróchnicowej w tej grupie chorych.
Summary
Introduction. Angelman syndrome is a rare neurogenetic disorder with an unexplained aetiology. The clinical picture varies depending on the patient’s genotype.
Aim. The purpose of this study was to present the facial features of Angelman syndrome as well as the hygienic, gingival and dental status of children with the syndrome.
Material and methods. An extra- and intraoral examination of patients with Angelman syndrome and generally healthy patients was performed, noting the presence of dysmorphic features, including facial shape and symmetry, skin and lip condition, gingival health and hygiene, dental caries, non-carious lesions, abnormalities of the size, shape, number and alignment of teeth in the dental arch. The results obtained were subjected to statistical analysis.
Results. Patients with Angelman syndrome were observed to have hypotonia of the orbicularis oris muscle, a large tongue and malocclusions. The study group had higher plaque index values than the control group (PLI, 1.42 ± 0.53 and 0.59 ± 0.38; p = 0.005, respectively). Gingival index was also higher, but the difference was not statistically significant (GI, 0.10 ± 0.18 and 0.00 ± 0.00; p = 0.147, respectively). Dental caries occurred at a similar frequency, but its severity was statistically significantly higher in the group with Angelman syndrome.
Conclusions. Patients with Angelman syndrome show features that predispose them to the development of dental disease. There is a need for continuous dental care and intensified caries prevention in this group of patients.
Introduction
Angelman syndrome (AS) is a neurogenetic disorder of unknown aetiology, the incidence of which is estimated at 1/12,000 to 1/20,000 live births worldwide (1, 2). Four molecular mechanisms of inheritance can be distinguished: deletion of the maternal copy of chromosome 15q11-q13 (del15q11-13, 70%); paternal uniparental disomy of chromosome 15q11-q13 (UPD, 2-7%); imprinting defects within chromosome 15q11-q13 that disturb the expression of maternally inherited UBE3A (3-5%); and maternally inherited UBE3A mutations (10%) (3). The clinical picture varies depending on the patient’s genotype. Chromosomal deletion usually causes the most severe symptoms, while patients with uniparental disomy or imprinting defects show a milder presentation. UBE3A mutations and imprinting defects may be associated with a high risk of recurrence in families (3-5).
The clinical manifestations that occur in all patients include significantly delayed functional development, speech and movement disorders, frequent smiling, and inability to focus for a longer period of time. Typical symptoms of AS develop around the age of 1 year and include severe intellectual disability, speech disorders, microcephaly, mandibular hypoplasia, macrostomia, prognathism, ataxia, and outbursts of laughter with hand-flapping movements (6-8). Additionally, individuals with AS suffer from limited attention span and hyperactivity. Among the AS symptoms, attention is drawn to a tendency to protrude or push out the tongue, eating disorders in infancy, epilepsy, widely spaced teeth, poor saliva control, excessive lip movements, as well as increased sensitivity to heat and fascination with water (3, 7). The diagnosis is based on clinical symptoms and in most cases can be confirmed with cytogenetic testing (9). Due to poorer physical activity, a tendency to obesity develops with age (10, 11).
In the neonatal and infancy period, the child’s face does not show any distinctive features, but it changes significantly with age. This is mainly caused by constant protrusion of the tongue and progressive prognathism. The central part of the face is hypoplastic with subtle facial features. The eyes are set deep and are relatively widely spaced. Epicanthal folds may be sometimes present. In older children, the pressure exerted by the constant tongue protrusion leads to gaps between the teeth and arched wear of the tooth crowns. The mouth is very large, with a thin upper lip. The chin is prominent and the lower part of the face widens at around 5 years of age (5, 7, 12, 13). Intellectual disability, motor disorders, including glossal and masticatory dysfunctions, as well as occlusal disorders may predispose to dental caries and gingivitis in AS children (14, 15). Few works have discussed the oral health status of children with this syndrome and these were usually case reports (14, 16, 17). In 2020, an analysis of the impact of AS on hard tissue mineralization in primary and permanent teeth was published, which showed hypoplasia and abnormal content of enamel proteins. Odontogenesis disorders may be a factor contributing to the development of dental diseases in patients with AS (18).
Aim
The aim of the study was to present the facial skeletal features in Angelman syndrome, as well as hygiene, gingival and dental status in the affected children.
Material and methods
Children with AS aged 3 to 18 years, who were patients of the Department of Genetics of the Children’s Health Memorial Centre Institute and the Department of Pediatric Dentistry of the Medical University of Warsaw, were qualified for the study. The control group consisted of generally healthy age-matched children reporting to the Department of Pediatric Dentistry of the Medical University of Warsaw. Diagnosis of Angelman syndrome by a clinical geneticist was a study group inclusion criterion. The exclusion criteria from the control group included other chronic general diseases or permanent pharmacotherapy (that may affect oral health, e.g. anti-asthmatic drugs, immunosuppressants); lack of written consent from the patient and/or parent/legal guardian, and poor patient cooperation preventing full examination. Written informed consent was obtained from study participants/parents before the study. The project was approved by the Bioethics Committee of the Medical University of Warsaw (No. KB/228/2009).
Interviews with parents/legal guardians and a clinical examination (intra- and extraoral) were conducted to collect data on the diagnosis of AS, genetic tests performed, and hygiene behaviours (who brushes the child’s teeth, frequency of tooth brushing, use of dental floss and mouthwashes).
During the extraoral examination, attention was paid to the presence of dysmorphic features typical of AS, including the shape and symmetry of the face, the condition of the skin, lips and corners of the mouth. The intraoral examination assessed:
• oral mucosa (the presence, type, location of lesions), salivary amount and consistency,
• gingiva around all teeth [the presence of developmental defects, recession, gingivitis using the Gingival Index (GI) according to Löe (19)],
• tongue (mobility, attachment of the tongue frenulum, size),
• palate (shape, arch height, developmental abnormalities),
• occlusal conditions and the presence of dental crowding, incorrect position of teeth in the arch – assessment for malocclusions,
• dentition, including:
? the presence of teeth with carious lesions [code ≥ 3 according to ICDAS II (20)], filled and missing teeth due to caries; the frequency and intensity of dental caries (DMFT and dmft) (21),
? the presence of developmental abnormalities in terms of the number and anatomical structure (shape, size) of teeth, as well as enamel defects. If missing tooth buds were suspected, a panoramic x-ray was taken. A modified Developmental Defects of Enamel Index (DDE index) was used to assess developmental abnormalities of enamel (22),
? oral hygiene (plaque index – PLI) (19).
Statistica 10 using the R 3.2.5 package (R Core Team 2019) was used for statistical analysis. Comparisons of fractions (dummy variables) between two groups were performed using the chi-square test, while comparisons of quantitative variables were performed using the Mann-Whitney U test. The significance level was set at p < 0.05.
Results
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Piśmiennictwo
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