Resident: Michael Hatton Mentor: Dr. Kane Date: 1.18.2017
Article Title: Osteogenesis Imperfecta: Clinical Diagnosis, Nomenclature, and Severity Assessment
Author(s): Van Dijk FS, Sillence DO
Journal: Am J Med Genet Part A 164A:1470-1481
Major Topic: Special Needs Patients: Osteogenesis Imperfecta
Type of Article: Expert Opinion
Main Purpose: Review of Osteogenesis nosology
Osteogenesis Imperfecta (OI) is a heterogeneous group of connective tissue disorders. The primary characteristic of these conditions is a lifelong susceptibility to fractures.
A total of 17 genetic causes of OI have been described; approximately 90% of OI patients of European descent have a mutation in the COL1A1/2 gene, and over 1,000 distinct mutations to this gene have been catalogued.
Due to the diverse presentation of OI, a severity grading scale has been proposed, based on clinical findings, historical data, fracture frequency, bone density, and impact on quality of daily life. Severity is graded Mild, Moderate, Severe, or Extremely Severe (See Figure III, below).
General Symptoms of OI include:
· Increased risk of osteoporosis, due to increased levels of both bone formation and resorption, with proportionally more resorption
· Increased risk of fractures, due to both primary fragility and secondary to osteoporosis
· Skeletal deformities, including scoliosis and basilar impression
· Dentinogenesis Imperfecta may or may not be present, depending on genotype
Classification of OI
· OI Type 1: Non-Deforming OI with Blue Sclera
o Blueness of the sclera
o Juvenile-onset hearing loss
o Skeletal deformities are rare
o Most often Autosomal Dominant inheritance
o Often of Mild or Moderate severity
· OI Type 2: Perinatally Lethal OI Syndromes
o Diagnostic hallmarks at 20 weeks gestation include crumpled limbs, bowing of long bones, and deformity of facial and cranial bones, with prenatal rib fractures
o Constant pain, no chance of normal quality of life
o Perinatal lethality: 20% are stillborn, 90% will die by 4 weeks
· OI Type 3: Progressively Deforming OI
o Multiple perinatal and childhood fractures lead to deformity
o Usually no blueness of the sclera at adulthood (may or may not be present at birth)
o Deficient growth, scoliosis
o Potential for pop-corn appearance to bone, thin osteopenic ribs, wormian skull bones
o Higher severity, can be fatal without intervention (chest wall deformity, pulmonary hypertension, and cardio-respiratory failure)
· OI Type 4: Common Variable OI
o No blueness of the sclera at adulthood (may or may not be present at birth)
o Hearing loss is rare
o Prevalence of skeletal deformities varies depending on genotype
o Most often Autosomal Dominant inheritance, though Autosomal Recessive and X-Linked cases have been documented
o Severity varies, even within families with the same genotype
· OI Type 5: OI with Calcification in Interosseous Membranes
o Characterized by progressive calcification of the interosseous membranes on the forearms and legs, with development of hyperplastic callus after insult to the bone, leading to swelling and pain
o Elevated serum alkaline phosphatase values
o Secondary effects lead to restriction of motion of the forearms and dislocation of the radial heads
o Moderate or Severe in presentation
The diversity of presentation seen in Osteogenesis Imperfecta is a challenge to treatment, because it is not possible to create treatment guidelines that are applicable to all patients. The fact that in the more common forms of OI, dentinogenesis imperfecta is often correlated to more severe presentation of OI means that there is a distinct population with both heightened dental needs and a greater need for special consideration with treatment, including impaired patient mobility, increased risk for trauma, and complications from bisphosphonate usage.
Level of Evidence: IV
Dr. Kane’s Comments:
It is a good review article on the clinical diagnosis, nomenclature , severity and the genetics of this very complex condition. It is important to understand the classification and the modes of inheritance and this article is important to provide patients and their families with insight into the probable course of the disorder.
Although not discussed in the article, we as pediatric dentists certainly want to be aware of the dental considerations. Are you aware there is a Osteogenesis Imperfecta Foundation that is helpful to parents and dentists raising and treating children with OI? Check it out at:
Please pay particular attention to treatment with bisphosphonates (aimed at reduction of osteoclast activity) which is mentioned in the article as well as the Foundation fact sheet. Also, I appreciated Table III in the article that nicely breaks down the severity grading scale of OI.
Just an FYI…..when I took my oral boards, they presented a history of a child with “brittle bones”. The entire case was on a child with OI so you all should pay attention to this condition as it has multiple dental considerations.
Good Luck and I hope this was helpful.