What every clinical geneticist should know about testing for osteogenesis imperfecta in suspected child abuse cases

  title={What every clinical geneticist should know about testing for osteogenesis imperfecta in suspected child abuse cases},
  author={Melanie G Pepin and Peter H Byers},
  journal={American Journal of Medical Genetics Part C: Seminars in Medical Genetics},
  pages={307 - 313}
  • M. Pepin, P. Byers
  • Published 1 December 2015
  • Medicine, Biology
  • American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Non‐accidental injury (NAI) is a major medical concern in the United States. One of the challenges in evaluation of children with unexplained fractures is that genetic forms of bone fragility are one of the differential diagnoses. Infants who present with fractures with mild forms of osteogenesis imperfecta (OI) (OI type I or OI type IV), the most common genetic form of bone disease leading to fractures might be missed if clinical evaluation alone is used to make the diagnosis. Diagnostic… 
COL1A1 and COL1A2 sequencing results in cohort of patients undergoing evaluation for potential child abuse
Routine testing for OI in the setting of child abuse when no other suggestive clinical findings are present has a low yield, and a careful review of the medical history and a detailed clinical evaluation help identify those at risk for genetic alterations.
Genetic causes of fractures and subdural hematomas: fact versus fiction
In this case-based review, mainstream medical practice allows for differentiation among the intracranial and skeletal manifestations of osteogenesis imperfecta, Menkes disease, glutaric acidemia type 1 and child physical abuse.
Evaluation of Fracture Without Known Trauma: Use of DXA in Differential Diagnosis
Role of bone densitometry in discriminating between healthy infants and children with possible NAI from those with OI is reviewed, including non-ambulant children with cerebral palsy and those with congenital insensitivity to pain who are prone to fragility fracture.
Clinical and Molecular Heterogeneity of Osteogenesis Imperfecta
In this book, the clinical presentations with particular emphasis on rare phenotypes associated with OI are discussed together with molecular advances in diagnosis and treatment of OI.
Genetic consultations in cases of unexplained fractures and haemorrhage: an evidence-based approach
The differential diagnosis for infantile fractures and subdural bleeds is discussed, cardinal signs and symptoms of genetic disorders are highlighted, and it is demonstrated that these genetic disorders can be readily differentiated and diagnosed using a stepwise approach.
Interpreting Osteogenesis Imperfecta Variants of Uncertain Significance in the Context of Physical Abuse: A Case Series.
Recommendations for careful and thorough evaluation are detailed, including proposed use of a limited follow-up skeletal survey in 3 months, as a consideration to assess healing of prior fractures and to look for any additional injuries.
Osteogenesis imperfecta in children and adolescents—new developments in diagnosis and treatment
Newer medications with anti-resorptive and bone anabolic action are being investigated in an attempt to improve on the efficacy of bisphosphonates but the safety and efficacy of these new approaches in children with OI is not yet established.
Osteogenesis imperfecta: diagnosis and treatment
Despite advances in the diagnosis and treatment of osteogenesis imperfecta, more research is needed and new antiresorptive and anabolic agents are being investigated but efficacy and safety of these drugs need to be better established before they can be used in clinical practice.
Current approach to diagnosis and treatment of children with osteogenesis imperfecta
Surgical treatment of the fractures and deformities of the extremities showed a positive effect on the patients’ quality of life, despite existing complications, and pharmacological treatment is based on bisphosphonate treatment, which increases the bone mineral density.


Testing for osteogenesis imperfecta in cases of suspected non-accidental injury
To evaluate if laboratory testing for osteogenesis imperfecta (OI) identifies children unrecognised by clinical examination in instances where non-accidental injury (NAI) is suspected as the likely
EMQN best practice guidelines for the laboratory diagnosis of osteogenesis imperfecta
Advances in the molecular genetic diagnosis of OI prompted new guidelines for molecular testing and reporting of results in which testing is also used to ‘exclude’ OI when there is suspicion of non-accidental injury.
Genetic heterogeneity in osteogenesis imperfecta.
An epidemiological and genetical study of osteogenesis imperfecta (OI) in Victoria, Australia confirmed that there are at least four distinct syndromes at present called OI. The largest group of
Rib Fractures in Osteogenesis Imperfecta: Have we Learnt Anything About Child Abuse?
We read with interest the recent paper by Greeley et al1 entitled “Fractures at diagnosis in infants and children with osteogenesis imperfecta” and the recent accompanying commentary by Paterson. We
Osteogenesis imperfecta without features of type V caused by a mutation in the IFITM5 gene
Screening for mutations in the IFITM5 gene is suggested in most cases of OI where type 1 collagen mutations are absent, as this report reports a 5‐year‐old child with clinical features of Oi type III or severe OI type IV and absence of classical features ofOI type V with a de novo recurrent IFITm5 mutation.
Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of the IFITM5 c.−14C>T mutation in all patients
Even though the disease-causing mutation is identical among patients with OI type V, the interindividual phenotypic variability is considerable.
Two mutations in IFITM5 causing distinct forms of osteogenesis imperfecta
One patient with a de novo c.119C>T heterozygous mutation in IFITM5, which predicts p.Ser40Leu mutation, is described, which developed hyperplastic calluses and had calcification of the forearm interosseous membrane.
Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation
A novel truncating deletion of exon 4 of TMEM38B is a novel candidate gene for AR OI, and future studies are needed to explore fully the contribution of this gene to AR Oi in other populations.
Distinct biochemical phenotypes predict clinical severity in nonlethal variants of osteogenesis imperfecta.
We reviewed clinical and biochemical findings from 132 probands with nonlethal forms of osteogenesis imperfecta (OI) whose fibroblasts were sent to the University of Washington for diagnostic studies
A cross‐sectional multicenter study of osteogenesis imperfecta in North America – results from the linked clinical research centers
OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV, and the mean lumbar spine area bone mineral density was low across all OI subtypes, those with more severe forms had lower bone mass.