Anna Matosek-Rutkowska1, Klaudia Lewandowska-Portas1, Aleksandra Bielecka1, *Ewa Krasuska-Sławińska1, 2
The appearance of the oral cavity in Sensenbrenner syndrome – a two cases report
Obraz jamy ustnej w zespole Sensenbrenner – opis dwóch pacjentów
1Dental Clinic for Children, Children’s Memorial Health Institute, Warsaw, Poland
Head of Clinic: Ewa Krasuska-Sławińska, MD, PhD
2Dental Surgery Clinic for Children and Adults, Children’s Memorial Health Institute, Warsaw, Poland
Head of Clinic: Ewa Krasuska-Sławińska, MD, PhD
1Poradnia Stomatologiczna dla Dzieci, Instytut „Pomnik – Centrum Zdrowia Dziecka”, Warszawa, Polska
Kierownik Poradni: dr n. med. Ewa Krasuska-Sławińska
2Poradnia Chirurgii Stomatologicznej dla Dzieci i Dorosłych, Instytut „Pomnik – Centrum Zdrowia Dziecka”, Warszawa, Polska
Kierownik Poradni: dr n. med. Ewa Krasuska-Sławińska
Streszczenie
Zespół Sensenbrenner (dysplazja czaszkowo-ektodermalna) jest rzadkim schorzeniem zaliczanym do grupy chorób określanych mianem ciliopatii, u podstawy których leży dysfunkcja rzęsek komórkowych związana z defektem kilku genów. Rzęski występują na powierzchni większości komórek człowieka, co oznacza, że proces chorobowy może dotyczyć wielu narządów i układów. Klinicznie objawy zespołu dotyczą twarzoczaszki, układu kostnego oraz skóry. Towarzyszyć temu może przewlekła niewydolność nerek i/lub schorzenia wątroby. Rozwój intelektualny pacjentów z CED jest prawidłowy. W jamie ustnej zaburzenia w rozwoju ektrodermy występują pod postacią hipodoncji, mikrodoncji, taurodontyzmu, wad rozwojowych guzków oraz szkliwa. Rozpoznanie CED stawiane jest na podstawie cech klinicznych, morfologicznych pacjenta oraz badań dodatkowych. Rokowanie zależne jest od stanu narządów objętych procesem chorobowym. Ze względu na podobieństwo objawów klinicznych CED wymaga różnicowania m.in. z zespołem Jeune’a czy Ellisa-van-Crevelda. Jednak ze względu na wieloukładowy charakter objawów klinicznych do leczenia, obserwacji i zapewnienia ciągłości opieki należy zaangażować wielodyscyplinarny zespół specjalistów, w tym również lekarzy stomatologów. W pracy przedstawiono przypadki dwóch pacjentów z zespołem Sensenbrenner, u których występowały zmiany w jamie ustnej.
Summary
Sensenbrenner syndrome, also known as cranioectodermal dysplasia (CED), is a rare genetic disease belonging to the group of diseases called ciliopathy, which is based on the dysfunction of cellular cilia associated with the defect of several genes. Cilia are present on the surface of the majority of human cells, which implies that pathological processes may affect multiple organs and systems. Clinically the symptoms of the syndrome concern facial skeleton, skeletal system and skin. It may be accompanied by chronic kidney failure and/or liver disease. In patients with congenital ectodermal dysplasia (CED), intellectual development remains preserved. However, ectodermal developmental disturbances are evident in the oral cavity, most commonly in the form of hypodontia, microdontia, taurodontism, and developmental defects of cusps and enamel. The diagnosis of CED is based on a combination of clinical and morphological characteristics, supported by additional diagnosis investigations. Prognosis is determined by the functional status of the organs involved in the pathological process. Given the overlap of clinical features, CED requires careful differential diagnosis from other syndromic entities, including Jeune syndrome and Ellis-van-Creveld syndrome. However, due to the multiply system of clinical symptoms, a multidisciplinary team of specialists, including dentists, should be involved in treatment, observation and continuity of care. Here, we present a case report of two patients with Sensenbrenner syndrome who had characteristic changes in the oral cavity.
Introduction
Sensenbrenner syndrome, also know as cranioectodermal dysplasia (CED), is a very rare syndrome of congenital defects (incidence < 1/1,000,000 births) inherited in an autosomal recessive manner (1-3). Sensenbrenner syndrome is classified as a ciliopathies, which are caused by abnormal structure and/or functioning of primary (immotile) cilia caused by mutations in the following genes: IFT122 (Intraflagellar transport 122, WDR10), IFT43 (Intraflagellar transport 43), IFT52 (Intraflagellar transport 52), IFT140 (Intraflagellar transport 140), WDR19 (WD Repeat Domain 19) and WDR35 (WD Repeat Domain 35) encoding IFT (intraflagellar transport) proteins belonging to complex A, which participates in retrograde intraciliary transport (4-6). Cilia are present on the surface of almost all human cells, which means that the disease process may involve many organs and systems, most often affecting the kidneys and liver (polycystic kidney disease, congenital fibrosis/cystic liver disease), leading to their chronic failure (5-9). The presence of cilia has also been found in odontoblast and ameloblast cells, where they participate in normal tooth morphogenesis (5, 10).
CED is primarily characterized by abnormalities of the craniofacial system, skeletal system, and ectodermal tissues, including teeth. Intellectual development in patients with CED is normal (3, 9). Clinically, patients exhibit abnormal skeletal development (craniosynostosis/dolichocephaly, narrow chest, syndactyly/polydactyly, joint hyperlaxity), sparse hair, and atypical, thin fingernails and toenails (1-5, 9). Some patients develop chronic renal failure due to nephronophthisis, while others experience liver dysfunction in the form of fatty liver disease (9). This group may also experience recurrent lung infections, heart defects, and ocular anomalies such as retinitis pigmentosa or retinal dystrophy. Ectodermal anomalies also manifest in the oral cavity in the form of hypodontia, microdontia, taurodontism, cuspal malformations and teeth with abnormal histological structure regarding enamel thickness (1, 10).
The diagnosis of CED is made based on the patient’s clinical and morphological features. Additional tests (imaging, laboratory) may be helpful, allowing for the detection of possible abnormalities in the functioning of the kidneys, liver, or eyes. Prognosis depends on the condition of these organs (4). Due to the similarity of clinical symptoms, CED requires differentiation from conditions such as Jeune syndrome or Ellis-van-Creveld syndrome (4).
The aim of the paper is to present the cases of two patients diagnosed with Sensenbrenner syndrome, in whom changes characteristic of this syndrome were observed in the oral cavity.
Patient description
Patient 1
The now 17-year-old patient was first referred to the Children’s Dental Clinic at the Institute for Children’s Healthcare (IPCZD) at the age of 2. Based on the interview, it was determined that the child was from a high-risk second pregnancy, delivered by cesarean section at 41 weeks. The child’s condition at birth was assessed at 8 points on the Apgar scale. The child’s length was 50 cm and birth weight was 3600 g.
At the time of presentation to the Dental Clinic, the girl was in good general condition and reported no oral pain. The patient also received ongoing multidisciplinary care for bilateral urinary tract dilatation and respiratory failure, and was undergoing genetic testing for suspected constrictive thoracic dysplasia and cranioectodermal dysplasia. Genetic testing, performed at the age of two using material collected from the girl and her parents, revealed a heterozygous mutation in axons 18 and 22 of the IFT121 (WDR35) gene, inherited from a heterozygous father and mother, respectively, confirming the diagnosis of Sensenbrenner syndrome.
In the following years, the patient developed chronic renal failure, which led to her being placed on an active kidney transplant list – a position she remains on to this day. An extraoral clinical examination revealed: a disproportionately small face with a pronounced frontal bone predominance (frontal thickening, high forehead), nasal recess in the facial skeleton, thin, fair hair, sparse eyebrows and eyelashes. The craniofacial examination revealed prominent features such as dolichocephaly (long head), slanting head, large and low-set ears, high forehead, hypertelorism, full cheeks, saddle nose, long, flat philtrum, and everted thick lips (fig. 1). An intraoral examination revealed no pathological lesions on the oral mucosa. Macroglossia was noteworthy. The primary dentition was age-inconsistent, with maxillary and mandibular central incisors and upper and lower first molars present, with significantly reduced clinical crown dimensions. The tooth surfaces were covered with plaque and deposits. Over the following years, the patient had irregular follow-up visits.
Fig. 1. 10-year-old female patient. Clinical symptoms of Sensenbrenner syndrome in the craniofacial area (dolichocephaly, plagiocephaly, satyr ears, high forehead, hypertelorism, full cheeks, saddle nose, long flat philtrum, everted and thick lips)
A dental examination performed 3 years later at the age of 5 revealed complete primary dentition without active caries lesions, gaps in the teeth and no pathological changes in the oral mucosa.
Another dental examination was performed on the patient at the age of 10. It revealed mixed dentition with carious lesions. The oral mucosa was shiny, smooth, and free of pathological changes. Oral hygiene was assessed as satisfactory. The lower anterior teeth were severely worn and conical in shape (fig. 2).
Fig. 2. Patient aged 10. Abnormal shape of lower incisors, gaps in the lower arch
During subsequent visits, the patient underwent conservative treatment of teeth with active caries and fluoride prophylaxis. During treatment at the Pediatric Dental Clinic, the patient underwent three panoramic X-rays. At the last examination, at the age of 17, the patient’s OPG revealed atypical mixed dentition, persistent teeth 55 and 85, as well as teeth 85, 46, and 47 with shaded fillings, missing tooth buds 18, 17, 27, 28, 38, 45, and 48, and an additional incisor on the left side of the mandible (fig. 3). The patient remains under the constant care of the Pediatric Dental Clinic at the Children’s Memorial Health Institute.
Fig. 3. A 17-year-old patient. Panoramic radiograph revealed: atypical mixed dentition, persistent primary teeth 85, 55, 75, permanent teeth 46, 47 with shading filling, missing tooth buds 18, 17, 27, 28, 38, 45, 48, rotation of teeth 14, 24, additional incisor on the left side of the mandible, conical shapes of the crowns of the incisors in the mandible
Patient 2
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Piśmiennictwo
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