Management of Osteogenesis Imperfecta: A Multidisciplinary Comprehensive Approach

Abstract

Osteogenesis imperfecta (OI) is a heterogeneous group of genetic skeletal disorders characterized by bone fragility and low bone mass, which manifests as multiple fractures and deformities of the spine and extremities. GENETICS OI is mostly inherited as an autosomal dominant trait; however, some cases are autosomal recessive. Mutations in type I collagen genes (COL1A1 and COL1A2) were found to be the most common causes of OI in 70%-80% of all cases, characterized by an autosomal dominant inheritance. Type V is the other autosomal dominant OI subtype, which is caused by a single recurrent mutation of IFITM5 (~10%). 1,2) To date, more than 10 OI genes of autosomal recessive trait have been identified (10%-15%). The 2019 version of the nosology and classification system of genetic skeletal disorders listed 17 genes under the name of OI. 3) Most of them are involved in the biosynthesis of type I collagen (COL1A1, COL1A2, CRTAP, LEPR1, PPIB, SERPINH1, FKBP10, and BMP1) or differentiation and function of osteoblasts (SP7, TMEM38B, WNT1, CRE-B3L1, and SPARC). However, the function of some genes responsible for the OI phenotype (IFITM5, SERPINF1, and TENT5A) has yet to be elucidated. Genetic testing is indicated when a clinical diagnosis is not obvious or when molecular confirmation is legally required such as differentiation from child abuse, exemption of military service, and so on. Because those having mutation of WNT1 or SERPINF1 are known to be less responsive to bisphosphonate treatment than other subtypes, 4,5) genotyping could be helpful in determining medical treatment. Considering numerous causative genes and their phenotypic similarity, it is more appropriate to test all the known OI genes simultaneously. Many of the OI genes such as COL1A1 and COL1A2 are huge in size and expensive to analyze via Sanger sequencing. Therefore, exome sequencing or target sequencing using panels of known OI genes via next-generation sequencing technology is the diagnostic test of choice for OI mutations. However, these methods cannot be used to detect large copy number variations including intragenic exonal deletions or duplications, which is an important limitation. The authors have conducted molecular genetic analysis using next-generation sequencing and/or Sanger sequencing in 177 Korean patients with OI and found that 96 patients (54%) carried COL1A1 mutations, 39 (22%)

Bruck Syndrome: Beyond the Obvious

“…Color version available online keeping with the Sillence and Glorieux classification of OI which classes this type as perinatally lethal [9], the estimated mortality rate of these patients in the first week of life is 80% [10]. Several cases have reported successful medical and surgical management of Bruck syndrome cases, ranging from bisphosphonates [11][12][13][14], orthopaedic interventions for fractures [1,4,15,16] to abdominal surgery for gastroschisis [5]. However, these patients were not reported to have intrauterine fractures, which may be indicative of a less severe form of Bruck syndrome.…”

Paper box fixation for femur fractures in an infant with osteogenesis imperfecta

“…Infants with OI often develop fractures during daily care even when caution is exercised. When splints or casts are used to treat fractures in infants with OI, additional splint‐ or cast‐associated fractures may occur owing to the bone fragility 1 . To date, safe methods of fixation without the use of splints or casts have not been established 2,3 .…”

“…When splints or casts are used to treat fractures in infants with OI, additional splint-or cast-associated fractures may occur owing to the bone fragility. 1 To date, safe methods of fixation without the use of splints or casts have not been established. 2,3 Here, we present our method of fixing femur fractures in an infant with OI using a paper box.…”

Patterns of femoral neck fracture and its treatment methods in patients with osteogenesis imperfecta

“…Osteogenesis imperfecta, a hereditary disease of the connective tissue, is characterized by bone fragility and low bone mass, which manifests frequent fractures and deformities of the spine and extremities [1]. Femur is the third most frequent bone associated with fractures in osteogenesis imperfecta patients, and mid-shaft is the most common site involved [2].…”