Skeletal Dysplasias

Overview

• Skeletal Dysplasias, also known as osteochondrodysplasias, are a clinically and phenotypically heterogeneous group of more than 450 inherited disorders characterized by abnormalities mainly of cartilage and bone growth although they can also affect muscle, tendons and ligaments, resulting in abnormal shape and size of the skeleton and disproportion of long bones, spine and head.
• They differ in natural histories, prognoses, inheritance patterns and physiopathologic mechanisms. They range in severity from those that are embryonically lethal to those with minimum morbidity. Approximately 5% of children with congenital birth defects have skeletal dysplasias. Until recently, the diagnosis of skeletal dysplasia relied almost exclusively on careful phenotyping, however, the advent of genomic tests has the potential to make a more accurate and definite diagnosis based on the suspected clinical diagnosis. The 4 most common skeletal dysplasias are thanatophoric dysplasia, achondroplasia, osteogenesis imperfecta and achondrogenesis. The inheritance pattern of skeletal dysplasias is variable and includes autosomal dominant, recessive and X-linked. 
• The Igenomix Skeletal Dysplasias Precision Panel can be used to make a directed and accurate differential diagnosis of skeletal abnormalities ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.  

Indication

The Igenomix Skeletal Dysplasias Precision Panel is indicated for those patients with a suspected clinical diagnosis of skeletal dysplasia presenting with the following manifestations: 

• Family history of skeletal dysplasia 
• Multiple spontaneous abortions or stillbirths in a family 
• Maternal hydramnios (excess amniotic fluid during pregnancy) 
• Fetal hydrops (fetal generalized edema) 
• Disproportionate short stature 
• Intellectual disability 
• Disproportionately large head 
• Other associated manifestations:
  • Ocular: Cataracts, myopia 
  • Oral cavity: Bifid uvula, cleft palate 
  • Central Nervous System (CNS): intracranial pathologic processes, neurologic impairment 
  • Skin: redundant skin folds, acanthosis nigricans 
  • Polydactyly 
  • Nails: Hypoplastic nails 
  • Joints: Multiple join dislocations 
  • Long bone fractures 
  • Heart: atrial septal defect, patent ductus arteriosus, transposition of great vessels 

Clinical Utility

The clinical utility of this panel is: 

• The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.  
• Early initiation of treatment with a multidisciplinary team, encompassing physical rehabilitation and surgical procedures, management of hearing and dental abnormalities, as well as drugs, such as vitamin D or gamma interferon.  
• Prenatal detection of osteopetrosis for a directed obstetric and perinatal treatment of affected infants. 
• Combining phenotypic and genotypic data to improve diagnostic rate of these patients in the target population as well as identification of mutations associated with unique disease complications.  
• Risk assessment of asymptomatic family members according to the mode of inheritance. 

Genes & Diseases