Johanson–Blizzard syndrome—A case study of oral and systemic manifestations

1. Introduction 

The Johanson–Blizzard syndrome (JBS) is a rare autosomal recessive disorder exhibiting various genetic abnormalities and a rough estimate of the incidence at around 1 per 250,000 [1]. JBS was first described in 1971 by Johanson and Blizzard [2] and since then approximately only 60 cases were related in the literature across the world [3]. The exact genetic cause of which is unknown. Transmission is felt to be autosomal recessive without sex predilection based on case histories that demonstrate a prevalence of consanguinity and familial pedigree data [4], [5], [6]. In 2005 was mapped the disease-associated locus to chromosome 15q14–21.1 and identified mutations, mostly truncating ones, in the gene UBR1 in 12 unrelated families with Johanson–Blizzard syndrome. UBR1 encodes one of at least four functionally overlapping E3 ubiquitin ligases of the N-end rule pathway, a conserved proteolytic system whose substrates include proteins with destabilizing N-terminal residues [3]. This condition is characterized by association of congenital exocrine pancreatic insufficiency and hypoplasia or aplasia of the nasal wings [1], [4], [7], [8], [9]. In addition, there are a number of variable abnormalities present in a high proportion of patients, including short stature, tooth abnormalities as oligodontia, sensorineural hearing loss, thin lips, mental retardation, midline ectodermal scalp defects, hypothyroidism, imperforate anus and genitourinary malformations [1], [4], [7], [8].

2. Case report 

An 18-year-old female, white, second daughter of parents consanguineous, presented for dentistry clinic for routine exams. Diagnosed with JBS the patient presented in the born imperforate anus and she was previously submitted three surgeries for reconstruction of this malformation. In the moment of the consult the patient presented in good general health condition, exhibiting slight mental retardation, normal breathing, with remarkable muscle development and vertebral deformity. In the physical examination observed that the patient exhibited low hair implantation, arranged so sparse in the scalp and a convergent strabismus. There was a facial asymmetry, characterized by mild hypertrophy of the right side of the face, left ptosis, ipsilateral eyebrow sparse, hypoplastic of the alae nasi (being more evident on the left side) in the midline ridge of the nose and the nasal septum deviation to the left and pronounced dimple (Fig. 1, Fig. 2). In the intra-oral clinical exam was observed atresia of the maxilla, groined palate (Fig. 3), bifid uvula and posterior alveolar ridge of the mandible showing reabsorption in both quarters, and identified a slight difficulty in mouth opening of the patient (Fig. 4, Fig. 5, Fig. 6). In the dental exam was observed the lack of tooth 12, 13, 22, 28, 36, 41, 42, 46 and 48 and microdontia of the tooth 31, 32, 33 and 43 (Fig. 7). Routine laboratory tests (hemogram, glycemia in fasting, ionogram, lipid profile, renal and thyroid) showed no change worthy of note, the serum levels of FSH, LH and prolactin also showed normal. Chromosomal karyotyping with bands was consistent with the female genus (46, XX).

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Fig. 1. Typical clinical appearance of Johanson-Blizzard syndrome showing hypoplastic of the alae nasi (being more evident on the left side) and eyebrow sparse.

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Fig. 2. Clinical appearance of profile.

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Fig. 3. Intra-oral clinical examination showing atresia of the maxilla, groined palate and absence of some teeth.

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Fig. 4. Intra-oral clinical examination showing absence of some teeth and microdontia of teeth 33 and 43.

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Fig. 5. Intra-oral image of right mandible of the patient.

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Fig. 6. Intra-oral image left mandible of the patient.

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Fig. 7. Panoramic showing microteeth, anodontia and enclosed tooth.

The hearing thresholds were preserved bilaterally and no abnormalities hypopituitary were observed in the nuclear magnetic resonance. Additionally, the patient no reported clinical or laboratory signs of pancreatic involvement.

3. Discussion 

Johanson–Blizzard syndrome is an extremely rare autosomal recessive disorder and most cases occur in consanguineously married couple [5], [6]. In the present case the patient was second daughter of parents consanguineously married and one would naturally consider the possibility of autosomal recessive inheritance, as described by Vieira et al. [6], Kulkarni et al. [9] and Beraldo et al. [7]. Our patient presented in the born recto-urogenital abnormalities, diagnosed as imperforate anus, hypoplastic of the alae nasi which characteristic features described in the literature [4], [5], [6], [7], [9].

Others features like dental abnormalities are also common in the literature [7], as described in this case where the patient exhibited absence of a significant number of tooth, thus requiring a proper dental planning for oral rehabilitation, which was routed by the practitioners of pediatric dentistry. Additionally, it highlights the deficiencies identified in the patient face, especially hypoplasia alae nasi and maxillary, corroborating the findings of Vieira et al. [6] and Kulkarni et al. [9].

The groined palate, bifid uvula, and areas of alveolar ridge reabsorption of the posterior mandible were additional findings identified in the patient reported, however these events were not found in previous reports of Johanson–Blizzard syndrome in the literature.

4. Conclusion 

The report of this case highlights the need for a multidisciplinary treatment for cases of rare syndromes that have significant amount of systemic manifestations, such as Johanson–Blizzard syndrome (JBS), noting the importance of involvement of dentists in order to identify the oral manifestations and to provide oral rehabilitation these patients.