Neurosurgical implications of osteogenesis imperfecta in children

2008 ◽  
Vol 1 (3) ◽  
pp. 229-236 ◽  
Author(s):  
Deanna Sasaki-Adams ◽  
Abhaya Kulkarni ◽  
James Rutka ◽  
Peter Dirks ◽  
Michael Taylor ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Genetic Disorder ◽  
Care Center ◽  
Spinal Fractures ◽  
Basilar Invagination ◽  
Bone Fragility ◽  
Shunt Insertion ◽  
Collagen Formation ◽  
Minimal Trauma ◽  
Sick Children

✓Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by disruption of normal collagen formation resulting in varying degrees of skeletal vulnerability, ligamentous laxity, and scleral discoloration. Children with OI may suffer from complex neurosurgical problems affecting the brain and spine. The authors sought to determine the neurosurgical implications of OI in a cohort of patients treated at a quaternary care center for pediatrics. The authors reviewed the case histories of 10 children with OI treated by the neurosurgical service at the Hospital for Sick Children in Toronto between January 1988 and March 2007. The cases of 4 of these children are highlighted in the article. The most common neurosurgical conditions encountered in this cohort included macrocephaly in 5 patients, subdural hematoma in 3 patients, epidural hematoma in 2 patients, and hydrocephalus in 3 patients. Basilar invagination and spinal fractures were observed in 20% of the cohort. Although some patients could be treated nonoperatively, several required craniotomy for clot evacuation, decompression, and spinal fixation for fracture or basilar invagination, and cerebrospinal fluid shunt insertion. Neurosurgical conditions affecting patients with OI include macrocephaly, the development of an acute intracranial hematoma after often minimal trauma, the development of chronic subdural fluid collections that may require drainage, hydrocephalus (both communicating and noncommunicating), basilar invagination, and subaxial spinal fractures. Surgery may be complicated in some children because of the underlying bone fragility and bleeding diathesis commonly observed in patients with OI.

Osteogenesis Imperfecta

2018 ◽  
Author(s):  
Aimee G. Kakascik
Keyword(s):  
Osteogenesis Imperfecta ◽  
Genetic Disorder ◽  
Bone Fragility ◽  
Type I ◽  
Multiple Fractures ◽  
Systemic Involvement ◽  
Collagen Formation ◽  
Different Types ◽  
Clinical Triad ◽  
Blue Sclerae

Osteogenesis imperfecta (OI) is a genetic disorder that affects collagen formation and ultimately leads to increased bone fragility. The fragile nature of the bones leads to fractures, even from seemingly normal patient care. Affected patients are at the highest risk for unintentional fractures during perioperative care. There are several different types of OI. Type I is the most common. With the different types come varying degrees of severity. Types II and III are the more severe forms. The classic clinical triad seen in OI is blue sclerae, multiple fractures, and conductive hearing loss. The patient may have other systemic involvement beyond the fragile musculoskeletal system. It is imperative that the anesthesiologist be well-versed in the natural history and perioperative management of patients with OI in order to optimize care and minimize complications.

scholarly journals Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated COL1A1 Gene in Osteogenesis Imperfecta

2021 ◽  
Vol 10 (14) ◽  
pp. 3141
Author(s):  
Hyerin Jung ◽  
Yeri Alice Rim ◽  
Narae Park ◽  
Yoojun Nam ◽  
Ji Hyeon Ju
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Disease Modeling ◽  
Bone Fragility ◽  
Osteogenic Potential ◽  
Type I ◽  
Gene Correction ◽  
Col1a1 Gene ◽  
Collagen Formation

Osteogenesis imperfecta (OI) is a genetic disease characterized by bone fragility and repeated fractures. The bone fragility associated with OI is caused by a defect in collagen formation due to mutation of COL1A1 or COL1A2. Current strategies for treating OI are not curative. In this study, we generated induced pluripotent stem cells (iPSCs) from OI patient-derived blood cells harboring a mutation in the COL1A1 gene. Osteoblast (OB) differentiated from OI-iPSCs showed abnormally decreased levels of type I collagen and osteogenic differentiation ability. Gene correction of the COL1A1 gene using CRISPR/Cas9 recovered the decreased type I collagen expression in OBs differentiated from OI-iPSCs. The osteogenic potential of OI-iPSCs was also recovered by the gene correction. This study suggests a new possibility of treatment and in vitro disease modeling using patient-derived iPSCs and gene editing with CRISPR/Cas9.

scholarly journals Osteogenesis imperfecta: a case report

2014 ◽  
Vol 43 (1) ◽  
pp. 30-32
Author(s):  
Ratu Rumana Binte Rahman ◽  
Shamasunnahar Begum
Keyword(s):  
Osteogenesis Imperfecta ◽  
Pulmonary Hypoplasia ◽  
Bone Fragility ◽  
Lower Limbs ◽  
Inherited Disease ◽  
Multiple Fractures ◽  
X Ray ◽  
Medical College ◽  
Minimal Trauma ◽  
Hallmark Feature

Osteogenesis Imperfecta is a inherited disease of connective tissue. Its hallmark feature is bone fragility with a tendency to fracture from minimal trauma or from the work of bearing weight against gravity. The disorder may occur in one out of 20,000 to one out of 60,000 live births, affecting both male and female of all races. We present a 38 year lady who gave birth to baby with osteogenesis imperfecta in Sir Salimullah Medical College & Mitford Hospital, Dhaka. Both lower limbs appeared shortened with thick musculo-cutaneous folds. Both the femoral shafts were shortened, deformed and fragmented. Both the humeral and fibular shafts were deformed and the presentation was breech. Her sclerae was blue. X-ray showed multiple fractures in humerus, femur and ribs and also right sided pulmonary hypoplasia. DOI: http://dx.doi.org/10.3329/bmj.v43i1.21376 Bangladesh Med J. 2014 January; 43 (1): 30-32

scholarly journals Dentinogenesis Imperfecta and Caries in Osteogenesis Imperfecta among Vietnamese Children

2021 ◽  
Vol 9 (5) ◽  
pp. 49
Author(s):  
Huong Thi Thu Nguyen ◽  
Dung Chi Vu ◽  
Duc Minh Nguyen ◽  
Quang Dinh Dang ◽  
Van Khanh Tran ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Genetic Disorder ◽  
Collagen Type I ◽  
Bone Fragility ◽  
Open Bite ◽  
Type I ◽  
Dentinogenesis Imperfecta ◽  
Type Iv ◽  
Brown Discoloration ◽  
Study Participants

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility and low bone mass, caused mainly by mutations in collagen type I encoding genes. The current study aimed to evaluate dentinogenesis imperfecta (DI), oral manifestations and caries status of OI children. Sixty-eight children (41 males, 27 females) aged from 3 to 17 years old (mean 9 ± 4.13) participated in the study. Participants were classified into three OI type groups (I—2 cases, III—31 cases and IV—35 cases). Clinical examination and an orthopantomogram were used to obtain prevalences and associations of DI, caries status, malocclusion, crossbite, open bite, eruption, impaction and missing teeth with OI. The prevalence of DI among OI patients was 47.1%, more common in OI type III than type IV. The yellow-brown discoloration type was more vulnerable to attrition than the opalescent-grey one in the primary dentition. OI seemed not to have a high risk of caries; the prevalence of caries was 69.1%. A high incidence of malocclusion, crossbite and open bite was observed. In-depth oral information would provide valuable data for better dental management in OI patients. Parents and general doctors should pay more attention to dental care to prevent caries and premature tooth loss.

scholarly journals A Founder Pathogenic Variant of PPIB Unique to Chinese Population Causes Osteogenesis Imperfecta IX

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenting Zhu ◽  
Kai Yan ◽  
Xijing Chen ◽  
Wei Zhao ◽  
Yiqing Wu ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Founder Effect ◽  
Chinese Population ◽  
Disease Incidence ◽  
Genetic Disorder ◽  
Missense Variant ◽  
Bone Fragility ◽  
Pathogenic Variant ◽  
Pathogenic Variants ◽  
Specific Allele

Background: Osteogenesis imperfecta (OI) is a heterogeneous genetic disorder characterized by bone fragility. PPIB pathogenic variants cause a perinatal lethal form of OI type IX. A limited number of pathogenic variants have been reported so far worldwide.Methods: We identified a rare pedigree whose phenotype was highly consistent with OI-IX. Exome sequencing was performed to uncover the causal variants. The variant pathogenicity was classified following the ACMG/AMP guidelines. The founder effect and the age of the variant were assessed.Results: We identified a homozygous missense variant c.509G > A/p.G170D in PPIB in an affected fetus. This variant is a Chinese-specific allele and can now be classified as pathogenic. We estimated the allele frequency (AF) of this variant to be 0.0000427 in a Chinese cohort involving 128,781 individuals. All patients and carriers shared a common haplotype, indicative of a founder effect. The estimated age of variant was 65,160 years. We further identified pathogenic variants of PPIB in gnomAD and ClinVar databases, the conserved estimation of OI type IX incidence to be 1/1,000,000 in Chinese population.Conclusion: We reported a founder pathogenic variant in PPIB specific to the Chinese population. We further provided our initial estimation of OI-IX disease incidence in China.

Hearing Loss in Finnish Adults with Osteogenesis Imperfecta: A Nationwide Survey

2002 ◽  
Vol 111 (10) ◽  
pp. 939-946 ◽  
Author(s):  
Kaija Kuurila ◽  
Reijo Johansson ◽  
Ilkka Kaitila ◽  
Reidar Grénman
Keyword(s):  
Hearing Loss ◽  
Osteogenesis Imperfecta ◽  
Clinical Features ◽  
Genetic Disorder ◽  
Nationwide Survey ◽  
Bone Fragility ◽  
Type I ◽  
Impaired Hearing ◽  
Hearing Ability ◽  
Blue Sclerae

Hearing loss, bone fragility, and blue sclerae are the principal clinical features in osteogenesis imperfecta (OI), a genetic disorder of connective tissue. In a nationwide search, an audiometric evaluation of 133 adult patients was performed. According to the criteria introduced by Sillence, type I was the most common form of OI. Of the patients with normal hearing on audiometry, 17.1% reported subjective hearing loss, and 19.1% of the patients with impaired hearing did not recognize it. On audiometry, 57.9% of the patients had hearing loss, which was progressive, often of mixed type, and mostly bilateral, and began in the second to fourth decades of life. The frequency or severity of the hearing loss was not correlated with any other clinical features of OI. Hearing loss is common, affecting patients with all types of OI. Subjective misjudgment of hearing ability supports the need for repeated audiometry in all OI patients. A baseline study at the age of 10 years followed by audiograms every third year thereafter is recommended.

scholarly journals Genotypic and Phenotypic Characteristics of 29 Patients With Rare Types of Osteogenesis Imperfecta: Average 5 Years of Follow-Up

2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Xi ◽  
Hao Zhang ◽  
Zhen-Lin Zhang
Keyword(s):  
Osteogenesis Imperfecta ◽  
Genetic Disorder ◽  
Healthcare Providers ◽  
Bone Fragility ◽  
Bisphosphonate Therapy ◽  
Mineral Density ◽  
Blood Biochemical ◽  
Significant Difference ◽  
Type V

Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility and abnormal connective tissue. Ninety percent of OI patients are caused by two mutations of COL1A1 and COL1A2, and more investigation was needed to better understand the rare types of OI. We followed up 29 patients with rare types of OI for an average of 5.4 years, and genotype, height, bone mineral density (BMD), blood biochemical indexes, misdiagnosis, and fracture were recorded. IFITM5 gene mutation was found in 18 patients (62.1%), which represents the most common pathogenic gene of rare types of OI in Chinese population. Thirteen cases had once been misdiagnosed, and the initial misdiagnosis rate was 44.8% (13/29). The higher misdiagnosis rate should be paid attention to by clinicians and healthcare providers, and we also give corresponding suggestions. Compared with the non-bisphosphonate treatment group, patients treated with bisphosphonates had higher lumbar spine BMD, fewer fractures, and lower levels of β-CTX and osteocalcin. However, there was no significant difference between OI type V patients and non-type V patients. Our study enriched the knowledge of genotype and phenotype characteristics of OI patients with rare types and bisphosphonate therapy.

Day Care for Sick Children

PEDIATRICS ◽  
1987 ◽  
Vol 79 (3) ◽  
pp. 445-446
Author(s):  
GEORGE G. STERNE
Keyword(s):  
Haemophilus Influenzae ◽  
Giardia Lamblia ◽  
Day Care ◽  
Hepatitis A ◽  
Care Center ◽  
Haemophilus Influenzae Type ◽  
Haemophilus Influenzae Type B ◽  
Type B ◽  
Day Care Center ◽  
Sick Children

Children in day care, like their home-reared peers, frequently become ill. Whether they are sick more frequently than those not in day care has been a question difficult to resolve because of the problem of appropriate control studies. Many pediatricians are convinced that this is so. There are data that infections due to certain specific agents including hepatitis A, Haemophilus influenzae type B, and Giardia lamblia occur more often in day-care center attendees. Clinical entities such as diarrhea, meningitis, and otitis media have also been shown to be more common in day-care center attendees. A recent review in Pediatrics1 provides a good overview of the problem.

Osteogenesis Imperfecta: Molecular and Mesoscale Disease Mechanisms

2009 ◽  
Author(s):  
Alfonso Gautieri ◽  
Sebastien Uzel ◽  
Simone Vesentini ◽  
Alberto Redaelli ◽  
Markus J. Buehler
Keyword(s):  
Mechanical Properties ◽  
Osteogenesis Imperfecta ◽  
Multiple Scales ◽  
Genetic Disorder ◽  
Single Point ◽  
Single Point Mutation ◽  
Mesoscale Simulation ◽  
Disease Mechanisms ◽  
Multiple Length Scales ◽  
Collagenous Tissues

Osteogenesis Imperfecta (OI) is a genetic disorder in collagen characterized by mechanically weakened tendon and fragile bones that affects more than 1 in 10,000 individuals. Even though many studies have attempted to associate specific mutation types with phenotypic severity, the mechanisms by which a single point mutation influences the mechanical behavior of tissues at multiple length-scales remain unknown. Here we show by a hierarchy of full atomistic and mesoscale simulation that OI mutations severely compromise the mechanical properties of collagenous tissues at multiple scales, from single molecules to collagen fibrils.

scholarly journals Prevalence and course of thyroid dysfunction in neonates at high risk of Graves’ disease or with non-autoimmune hyperthyroidism

2021 ◽  
Vol 184 (3) ◽  
pp. 431-440
Author(s):  
Hassina Benlarbi ◽  
Dominique Simon ◽  
Jonathan Rosenblatt ◽  
Cecile Dumaine ◽  
Nicolas de Roux ◽  
...  
Keyword(s):  
High Risk ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Genetic Disorder ◽  
Care Center ◽  
Receptor Gene ◽  
High Serum ◽  
Pediatric Care ◽  
Graves Disease ◽  
Neonatal Hyperthyroidism

Objective Neonatal hyperthyroidism may be caused by a permanent non-autoimmune genetic disorder or, more frequently, by maternally transmitted high serum TRAb levels. Variable thyroid dysfunction may be observed in this second context. We aimed to evaluate the prevalence of neonatal non-autoimmune hyperthyroidism and of the different types of thyroid function in neonates with a high risk of hyperthyroidism due to maternal Graves’ disease (GD). Design and methods This observational cohort study included all neonates identified in the database of a single academic pediatric care center, over a period of 13 years, as having non-autoimmune hyperthyroidism or an autoimmune disorder with high TRAb levels (above 6 IU/L) transmitted by their mothers. Patients were classified as having neonatal hyperthyroidism, hypothyroidism, or euthyroidism with a permanent or transient disorder. Results Two of the 34 consecutive neonates selected (6%) had permanent non-autoimmune hyperthyroidism due to germline (n = 1) or somatic (n = 1) mutations of the TSH receptor gene. The patients with high serum TRAb levels at birth had transient hyperthyroidism (n = 23), hypothyroidism (primary n = 2, central n = 3) or persistent euthyroidism (n = 4). Conclusion These original findings highlight the need for careful and appropriate monitoring of thyroid function in the long term, not only for the rare patients with non-autoimmune neonatal hyperthyroidism, but also for repeat monitoring during the first month of life in neonates with maternally transmitted high TRAb levels, to ensure the early identification of thyrotoxicosis in more than two thirds of cases and to detect primary or central hypothyroidism, thereby potentially decreasing associated morbidity.

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