Craniosynostosis in Alagille syndrome

Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
American Journal of Medical Genetics (Impact Factor: 3.23). 10/2002; 112(2):176-80. DOI: 10.1002/ajmg.10608
Source: PubMed

ABSTRACT Alagille syndrome is a multisystem developmental disorder with primary involvement of the liver, heart, skeleton, eyes and facial structures, and demonstrates highly variable expressivity with respect to all of the involved systems. Alagille syndrome is caused by mutations in the Jagged1 gene. Jagged1 is a ligand in the Notch signaling pathway that has been shown to regulate early cell fate determination. Mutations in Jagged1 have been identified in approximately 80% of patients with Alagille syndrome. We have recently identified two patients with mutation proven Alagille syndrome who also had unilateral coronal craniosynostosis. Both individuals were screened for mutations in fibroblast growth factor receptor 1, 2, 3 and TWIST genes, all associated with various types of craniosynostosis and no mutations were identified. The finding of a conserved form of craniosynostosis in two unrelated patients with Alagille syndrome and mutations in Jagged1 may indicate that Jagged1 plays a role in cranial suture formation.

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Available from: Catherine A Stolle, Oct 30, 2014
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    ABSTRACT: Abstract Alagille syndrome is a rare, autosomal, complex, dominant disorder associated with dysfunction of the liver, heart, skeleton, and eyes, as well as characteristic facial appearance. It is associated with the defect in component of the Notch signalling pathway. Here, we review the main features of Alagille syndrome with special focus on oro-facial manifestations like prominent forehead, moderate hypertelorism with deep-set eyes, a saddle or straight nose with a flattened, bulbous tip, and large ears. The article is based on the most recent and significant literature available from the Medline database. Contrary to healthy children, patients with Alagille syndrome have many problems, depending on several factors like the severity of cholestasis and scarring in the liver, heart or lung problems, presence of infections, or other problems related to poor nutrition that can manifest in their oral cavity in the dental and periodontal tissues, as well as oral mucosa. From the dentist's view, the most important elements are careful observation, accurate diagnosis, and planned management of such patients, especially during the patient's formative years, to prevent complications. Aggressive preventive oral care and consultations with medical specialists before any invasive procedure are obligatory. All this can improve quality of life in patients with Alagille syndrome.
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    ABSTRACT: Alagille syndrome is associated with various ocular abnormalities, including pseudopapilledema or optic disk edema due to increased intracranial pressure. Several mechanisms have been proposed to explain the mechanism of intracranial hypertension in Alagille syndrome. Craniosynostosis is an unusual but significant cause of increased intracranial hypertension in Alagille syndrome. It has recently been demonstrated in animal models that Jagged1 gene in which mutations are responsible for Alagille syndrome may also take part in cranial suture formation. We report a child with Alagille syndrome and craniosynostosis who presented with pruritus, elevated liver enzymes, and suspected increased intracranial pressure.
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    ABSTRACT: This case report offers a multidisciplinary interpretation of the violent death of a 4-year-old girl suffering from Alagille syndrome who died after a low-height fall that resulted in temporal bone fracture and a large epidural hematoma. The article evidences the macroscopical and microscopical characteristics of the syndrome, focusing especially on the skeletal findings that emerged during autopsy. In the case report, distinction is made between a possible accidental or non-accidental nature of the injuries and the characteristics of the injury have been interpreted in the light of the existing data on Alagille syndrome. In conclusion, the death was documented asaccidental since abnormalities in the skeletal system evidenced during autopsy have predisposed the death of the child albeit through a very mild head trauma. The case report evidences the importance of studying features of skull macro- and microstructure in patients with Alagille syndrome, which have been, until now, underreported in literature and which might contribute to fracture vulnerability in these patients. Although rare, Alagille syndrome is a condition that should be known to forensic medicine practitioners and whose features and peculiarities must be taken into consideration in pediatric autopsy and suspected child abuse cases.
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