Dental abnormalities and preventive oral care in Schimke immuno-osseous dysplasia

Abstract

Background

Schimke immuno-osseous dysplasia (SIOD) is a rare, severe, autosomal recessive disorder that results in spondyloepiphyseal dysplasia, renal dysfunction, immunodeficiency, facial dysmorphism and growth failure. Little is known about oral features associated with SIOD. Some of the dental anomalies encountered are specific to SIOD and have only been reported in individuals with SIOD.

Case report

This paper describes the clinical and radiographic dental manifestations of SIOD in two Caucasian brothers. Both lived to be about ten years old. After a variety of symptoms were reported, a diagnosis of SIOD was finally made when the brothers were respectively 5 and 8 years old. At that time, dental anomalies, such as dyschromia, bulbous crowns, short and thin roots, had not been taken into account to establish the diagnosis. However, knowledge of the dental features characteristic of this disease could have helped make the diagnosis. Although both were caries- and periodontal disease-free, special attention was focused on prevention, including dietary counselling, plaque control, oral hygiene instructions and the use of fluoridated toothpaste.

Follow-up

The two patients were followed every six months, for over 2 years (until their death), by both a private dentist and a university hospital dentist, which helped them maintain good oral health. Oral hygiene was assessed at each appointment and fissure sealants were placed by the private practitioner on their first permanent molars.

Conclusion

This report describes dental anomalies specific to SIOD that could facilitate diagnosis. Clinicians and dentists should work in collaboration to diagnose and treat children with SIOD. These patients require regular and specific dental management because of their fragile health and their characteristic dental anomalies. Ideally, preventive visits should be scheduled every six months in addition to curative visits as needed.

Background

Schimke immuno-osseous dysplasia (SIOD) is a rare, severe, autosomal recessive disorder that results in spondyloepiphyseal dysplasia, renal dysfunction, immunodeficiency, facial dysmorphism and growth failure [Ludman et al., 1993]. The dysmorphic features of SIOD include a triangular face, broad nasal bridge, bulbous nose tip, small palpebral fissure, short neck, low hairline, protuberant trunk and short limbs. Although neurological symptoms such as headaches and stroke have been reported [Boerkoel et al., 2000, Baradaran-Heravi et al., 2002, Lou et al., 2002], intelligence is generally normal.

The only known molecular cause of SIOD is biallelic mutations of the SMARCAL1 gene [da Fonseca, 2000, Lucke et al., 2004, Elizondo et al., 2006, Clewing et al., 2007]. This gene encodes an SnF2 family protein that is involved in chromatin remodelling [Lou et al., 2002, Clewing et al., 2007, Yusufzai and Kadonaga, 2008, Yuan et al., 2009].

SIOD is generally fatal, and the only treatments are symptomatic, such as renal transplantation to treat renal failure [Boerkoel et al., 2000, Elizondo et al., 2006]. The severity of SIOD follows a continuum. Individuals with juvenile onset disease survive into adulthood and usually die when they are in their teens or twenties, whereas individuals with infantile onset disease usually do not live beyond the first decade of life [Hashimoto et al., 1994, Rodrigo et al., 2001, Lucke et al., 2004].

Little is known about oral features associated with SIOD. In a recent paper, dental anomalies were found in 66% of SIOD patients with biallelic SMARCAL1 mutations. Microdontia and hypodontia were shown to be present in respectively 46.8% and 52.3% of the patients studied, while 72% of them had molar root hypoplasia. The disproportion between the molar crown and root could be severe in some cases. Bulbous molar crowns were commonly found as well as a particular radiopacity of primary and permanent molars. Increased caries was regularly found whatever the degree of severity of the disease [Morimoto et al., 2012].

Individuals with SIOD frequently face a long search for a diagnosis, and information about the dental abnormalities of SIOD could be a diagnostic aid. Accordingly, the dental abnormalities of two brothers with SIOD, and their dental management, are reported here.

Case report

Medical history

This case report describes two Caucasian young brothers, Patients 1 and 2, who were hospitalized in the paediatric department of Rennes University Hospital in France. The clinical characteristics of the two patients are reported in Table 1.

Table 1.

Clinical finding of two brothers with Schimke immuno-osseous dysplasia.

Characteristics	Patient 1	Patient 2
Birth parameters
Gestational age (GW)	35	35.5
Birth weight (kg)	1.49	1.49
Birth length (cm)	41	41.5
Birth complications	X	X
Growth parameters
Developmental delay	X	X
Physical and facial features
Short neck	X	X
Short trunk	X	X
Exaggerated lumbar lordosis		X
Protruding abdomen	X	X
Broad depressed nasal bridge	X	X
Bulbous nasal tip	X
Elongated upper lip	X	X
Skeletal abnormalities
Retarded bone age	X	X
Spondyloepiphyseal dysplasia	X	X
Ovoid dorsally flat vertebrae	X	X
Hypoplastic pelvis	X
Abnormal femoral heads	X	X
Ocular abnormalities
Corneal opacities		X
Dermatologic abnormalities
Pigmented spots	X	X
Hair	Sparse	Sparse
Haematologic Abnormalities
Anaemia
Thrombocytopenia		X
Neutropenia	X
Lymphopenia	X	X
Renal dysfunction
Age at onset of renal dysfunction (years)	4.5	3.5
Nephrotic syndrome	X	X
Progressive renal failure	X	X
Hypertension	X	X
Dialysis	X	X
Kidney transplant	X	X
Immune dysfunction
Recurrent infections	X	X
Lymphopenia	X	X
Endocrine dysfunction
Abnormal thyroid function	X	X
Abnormal growth hormone levels
Vascular dysfunction
Cerebral infarcts		X
Cerebral moyamoya
Sex	M	M
Age of death (years)	10	9

X present; blank absent or not known.

Both boys were born prematurely and were small with low birth weights. Soon after birth, developmental delays became evident along with physical and facial abnormalities, including short neck, short trunk, exaggerated lumbar lordosis, protruding abdomen, broad depressed nasal bridge, bulbous nasal tip and elongated upper lip. Their bone development was delayed. The two brothers had spondyloepipheseal dysplasia, ovoid dorsally flat vertebrae and abnormal femoral heads. Patient 1 had also a hypoplastic pelvis. Patient 2 had ocular abnormalities such as corneal opacities. Both patients had pigmented spots and sparse hair. Haematologic abnormalities were found, and renal dysfunction started between the ages of 3 and 5 years in both patients. These abnormalities were associated with immune dysfunction and vascular dysfunction. After several years of symptomatic treatment, the collective symptoms were used to make an SIOD diagnosis at age 5 years (Patient 1) and 8 years (Patient 2). At that time, genetic research had begun to try to determine the mutation responsible for the disease, but this information was not determined before the patients died. Both patients were first seen by a private dentist at the age of respectively 3 and 5. Because of their unusual oral characteristics, this practitioner sent the patients to a specialist in paediatric dentistry.

Oral clinical examination

Patient 1 (younger brother) had mixed dentition with grey-yellow discolouration (Figure 1E). There was a diagnosis of microdontia as his anterior teeth were small and widely spaced (Figure 1A, E, F). The child was caries-free and had normal periodontal tissues.

Figure 1.

X-rays and a photograph of Patient 1 at age 7 years. (A) Panoramic radiograph; (B) upper left posterior region; (C) lower left posterior region; (D) lower right posterior region; (E) photograph of the patient’s anterior teeth; (F) radiograph of the upper left anterior region.

Patient 2 also had grey-yellow discolouration of his teeth (Figure 2). The patient was 7 years old when the photograph was taken. The boy had the same oral status as patient 1 except microdontia.

Figure 2.

Photograph of patient 2’s anterior teeth at age 7 years.

Radiographic examination

Dental radiographs were obtained when Patient 1 was 7 years old (Figure 1).

On the panoramic X-ray (Figure 1A), the dental age was appropriate for the patient’s chronological age. There was agenesis of the maxillary and mandibular second premolars and agenesis of the left mandibular first premolar. The existing teeth had bulbous crowns and marked cervical constriction, resulting in bell- or tulip-shaped teeth. The teeth showed obliterated pulp chambers, short and thin roots and a marked radiopacity of the crowns (Figure 1A–D). There was a diagnosis of microdontia as his anterior teeth were small and widely spaced (Figure 1A, E, F). The radiographic aspect of the periodontal tissues appeared to be normal.

Radiographs from patient 2 were performed by the private dentist using conventional screen-film technique and could not be used because of their poor quality. However the teeth showed similar characteristics to those from patient 1 (i.e. bulbous crowns, obliterated pulp chambers, short and thin roots).

Treatment

The boys both received dental care once while admitted at the hospital and subsequently were treated in private practice. Although the brothers were caries- and periodontal disease-free, special attention was focused on prevention. The children and their parents were taught brushing techniques and the importance of tooth cleaning by the university hospital dentist. Fluoridated toothpastes adapted to the patients were prescribed and advices about nutrition were given to the mother. No topical fluoride other than toothpaste was applied due to the absence of caries.

Follow-up

From the moment of the first oral examination, both children were followed by both the private practitioner and the university hospital dentist every 6 months until their death. Emphasis was put on preventive cares. The efficacy of tooth brushing was assessed at each appointment and fissure sealants were placed by the private practitioner on their first permanent molars. All treatments were performed easily and successfully. Because of careful dental management, the patients were not subjected to any complicated or invasive procedures.

Discussion

Specific dental abnormalities

The two patients described in this study had a dental age that was appropriate for their chronological age, normal cementum and normal periodontal tissues. The boys also had dyschromia, high radiopacity of the molars, obliterated pulp chambers, bulbous crowns, and short and thin roots. The shapes of the crowns and roots described are very specific to SIOD and have only been reported in individuals with SIOD [da Fonseca, 2000, Morimoto et al., 2012]. Microdontia found in patient 1 is also a common oral feature of this disorder as well as hypodontia. Agenesis of the second premolars is consistent with previous findings indicating that premolars are most frequently absent [Morimoto et al., 2012].

Impact of these findings

A diagnosis of SIOD is difficult since no features of the disorder are invariant. In addition, complementary diagnosis by molecular testing may be difficult to perform since all of the genetic causes of SIOD have not been identified. Identifying features specific to SIOD such as the dental anomalies described here is therefore important. In this context, a dental panoramic radiograph for individuals with severe growth restriction and corticosteroid-resistant nephrotic syndrome might dramatically shorten the diagnostic odyssey for SIOD patients.

The peculiar tooth anomalies observed in SIOD patients might also provide insights into the pathophysiology of the disease. Specifically, these findings suggest that errors in the replication forks caused by mutation of the SMARCAL1 gene alter genetic cascades necessary for tooth formation.

Appropriate clinical management

Parents with a child with SIOD should consider professional dental care as part of managing the disease. Good dental care will likely help SIOD patients maintain general good health by preventing infections and pain and by improving their ability to have good nutrition and a pleasant appearance, thus contributing to their well-being. This paper shows that cooperation between private practitioners and hospital dentists may be beneficial in the management of oral health in these patients.

In providing dental care to individuals with SIOD, dentists should consider several issues including the general condition, medical history and current medical treatments of the patient, with special emphasis on immunological status. Other systemic problems such as renal failure and hypertension should also be taken into account. Antibiotic prophylaxis should be used in the case of invasive care, again keeping renal dysfunction in mind. Second, oral cares must take into account the particular dental status of an SIOD patient. For example, brittle enamel leads to an increased risk of tooth decay. Dental caries has been shown to be regularly present in patients with SIOD [da Fonseca, 2000, Morimoto et al., 2012]. Dental care should include dietary counselling, plaque control, oral hygiene instructions, daily fluoride mouth rinses or the use of fluoridated toothpaste, professional topical fluoride application, and sealants if necessary. Restorative care is possible. Moreover, crowns or composite resin reconstruction can be used for microdontia. Partial dentures can be placed to maintain space, improve mastication, aesthetic, and speech issues related to agenesis. Third, although malocclusion is correctable with orthodontic treatment, tooth movement should be avoided due to short and thin roots. It may be possible to move the teeth very slowly. Obliterated pulp chambers complicate the management of endodontic treatment. Lastly, precautions must be taken to avoid bacteraemia during scaling, surgery, and endodontic treatment.

Conclusion

There is no general consensus regarding the optimal dental management of SIOD patients. However providing successful dental management of SIOD patients in combination with paediatric care remains possible. Nevertheless, as the life expectancy of these patients is reduced and their medical care is complex, dental care should be based on providing minimal but sufficient care so as not to inflict long and tedious treatments, such as orthodontic and prosthetic treatments, on children with SIOD.

Patient management requires teamwork. Clinicians should contact dentists to help make a SIOD diagnosis, and dentists should collaborate with clinicians to help treat the patient. Dental findings play an important role in SIOD. More accurate descriptions of dental findings that are characteristic of SIOD may help in diagnosis and treatment.