ESPE Abstracts

Introduction: Bone dysplasias are a group of disorders affecting the development and growth of bones and cartilage. These conditions can lead to various skeletal abnormalities, including short stature, deformities and problems with joint function. Skeletal dysplasias are generally caused by genetic mutations. There are over 400 different types of bone dysplasias, each with its specific set of symptoms and genetic causes. This study introduces three patient cases of rare bone dysplasias: Spondyloepiphyseal dysplasia tarda, Wiedemann-Steiner syndrome and Omodysplasia type 1.

Methods: Next generation sequencing (NGS) custom panel of 1023 genes associted with bone anomalies was examined in our three patients. Sequencing was performed on the Illumina platform on the NextSeq^TM 500/550 device. Causal variants were verified using Sanger sequencing.

Results: The first case report is about a 51-year-old men examined for disproportionately short stature with shortened torso, short neck, hypoplastic auricles, hyperlordosis of the lumbar spine and digital clubbing. The NGS panel revealed a hemizygous splicing variant c.238+1A>G, p.(?) in the TRAPPC2 gene causing X-linked recessive spondyloepiphyseal dysplasia tarda. The second case report involves a fetus from the third pregnancy of healthy parents. Ultrasound revealed generally shortened limbs. Examination of the chorionic villus sampling (CVS) uncovered a homozygous single base deletion c.778del, p.(Leu260PhefsTer4) in GPC6 gene causing autosomal recessive Omodysplasia type 1. The third case report concerns a child of healthy parents, a boy from the second pregnancy. The patient was examined for nonspecific facial stigmatization, delayed psychomotor development, congenital stridor, left hemisyndrome and plagiocephaly. Proband’s DNA revealed a de novo causal variant c.2584C>T, p.(Arg862Ter) in KMT2A gene in the heterozygous state. The case was diagnosed as autosomal dominant Wiedemann – Steiner syndrome.

Conclusion: In recent years, it has been shown that genetics plays an important role in establishing an accurate diagnosis. Finding the correct diagnosis can have a profound impact on both current and future generations, particularly in the context of genetic disorders such as bone dysplasias. A multidisciplinary team of healthcare providers, including geneticists, orthopedic surgeons, endocrinologists, and physical therapists, is required based on this diversity to provide comprehensive care for affected individuals.