Alagille syndrome (ALGS) is a multisystem disorder most commonly caused by a mutation in JAG1. Its main pathological features are liver and heart disease. Less commonly noted are its oral manifestations.
How does ALGS contribute to oral disease? It is closely associated with congenital hyperbilirubinemia, which is thought to cause structural abnormalities and green discoloration in the teeth during development. In addition, bilirubin accumulates in mineralized tissues for a period of time until complete remodeling occurs; however, remodeling does not take place in dental mineralized tissues, leading to continued bilirubin storage.
“The greenish color of the teeth is the most striking feature of this syndrome, which presents an unfavorable prognosis and, to a great extent, affects patients’ psychological aspects,” Anacleto and colleagues wrote in Special Care in Dentistry.
The characteristic green discoloration of the teeth is commonly observed in children who have serum bilirubin levels above 30 mg/dL, affecting both the primary and permanent dentition. In addition, a toxic combination of coagulation disorders, food deficiency, and decreased immunity can drive oral disease.
The Harmful Effects of Teeth Discoloration
Anacleto and colleagues detailed the case of a pediatric patient with ALGS and oral manifestations of the disease. The patient was a 10-year-old female who presented with greenish and oddly shaped teeth, which had led to her being bullied in school.
The patient was diagnosed with ALGS shortly after birth via genetic testing. She had jaundice, chronic cholestasis, bile duct paucity, a cardiac murmur, and facial dysmorphism typically seen in ALGS.
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Her clinical condition deteriorated, resulting in severe chronic cholestasis and liver cirrhosis. A combination of immunodeficiency and hepatic deficiency resulted in a hematogenic form of osteomyelitis in the bones of her lower limbs. She subsequently underwent a liver transplant.
Upon her latest presentation, her physicians noted facial dysmorphism, short stature, and low body weight. Intraoral findings revealed that she had normal dental development for her age. However, her clinicians discovered a number of oral abnormalities associated with ALGS. For example, all of her teeth had greenish/brownish discoloration. Her right maxillary lateral incisor was found to be shaped conically (Angle class III). She also had anterior crossbite, crowding in both dental arches, and maxillary atresia.
“Although the oral mucosa was normal with no evidence of color change, the gingivae, especially around the anterior teeth, showed evidence of inflammation and mild gingival swelling,” Anacleto et al wrote.
Because the patient was only 10 years old and would still continue to grow, her physicians decided to take a conservative course of action, recommending the clinical treatment of caries lesions and dental prophylaxis. Orthodontic treatment, the reversal of Angle class III, and orthognathic surgery would only be undertaken after craniofacial growth had ceased.
Her guardians were advised about good oral hygiene, which in any case is highly important in patients with ALGS and a history of liver transplantation. Since the esthetic correction of the discoloration of the patient’s teeth would only be undertaken after surgery, the patient was offered psychological support to deal with her self-esteem and bullying issues.
Oral Disease After Liver Transplantation
“Many oral/dental changes occur after liver transplantation, which is very often necessary in patients with Alagille syndrome,” Berniczei-Royko and colleagues wrote in Medical Science Monitor.
One of the key reasons the oral cavity is so vulnerable to disease is that it hosts a variety of pathogenic bacteria. These bacteria can result in dental infections, as well infections in other organs, giving rise to pneumonia, peptic ulcers, and infective endocarditis. A person who has undergone an organ transplant tends to be immunologically vulnerable to infection.
Read more about ALGS epidemiology
This is why it is vital that the extent of oral disease is carefully characterized before and after liver transplantation. Post-surgery, patients are advised to attend regular dental check-ups in order to prevent any oral damage from being missed.
The management of oral disease in a patient with ALGS requires close coordination between the patient’s physician and dentist. This is important to ensure that there is no overlap in the drugs prescribed. Patients with ALGS who have undergone liver transplantation are typically prescribed a number of drugs for both immunosuppression and prophylaxis against opportunistic infections.
As highlighted in the case study, there is also a psychological element of ALGS oral disease that should not be overlooked. The combination of facial dysmorphism and dental abnormalities can result in low self-esteem, which is made worse by peer comparison and bullying.
In the case of the 10-year-old patient, her treatment had to be delayed because her craniofacial growth was still ongoing. This meant that her primary concern, ie, the abnormal discoloration and shape of her teeth, could not be completely addressed. Therefore, psychological distress is likely to continue unless support is given in this area.
This demonstrates the importance of a multidisciplinary framework in treating the oral manifestations of ALGS; in this case, the dental, medical, and psychiatric disciplines. As ALGS is a chronic disease, the patient would require consistent follow-up and care in order to preserve quality of life.
Berniczei-Royko A, Chałas R, Mitura I, Nagy K, Prussak E. Medical and dental management of Alagille syndrome: a review. Med Sci Monit. 2014;20:476-480. doi:10.12659/MSM.890577
Bonnet AL, Greset V, Davit-Beal T. Oral manifestations of Alagille syndrome. BMJ Case Rep. 2020;13(5):e234689. doi:10.1136/bcr-2020-234689
Anacleto MA, Melo CFR, Oliveira RP, da Silva LCP, Taitson PF. Alagille syndrome: oral manifestations — a case report. Spec Care Dentist. 2021;41(6):741-749. doi:10.1111/scd.12623