Geleophysic dysplasia: one gene, different phenotypes

Geleophysic dysplasia (GD) is a rare multisystem disorder that affects bones, joints, heart, and skin. Mode of GD inheritance varies and can be autosomal recessive in case of ADAMTSL2 gene mutations and autosomal dominant in case of FBN1 and LTBP3 genes mutations. In the article we present an example of our own examination of two patients from different families, with different GD clinical picture, but with a common trait of pronounced dwarfism resistant to treatment with growth hormone. In the course of usual endocrine tests there has been no primary endocrine pathology detected. We have conducted genetic research in each family by method of exomic sequencing. In both patients we have identified de novo FBN1 heterozygous mutations p.Tyr1696Asp and p.Cys1748Ser. Both children had common clinical symptoms, such as pronounced dwarfism, distinctive facial features, short limbs, as well as joint contractures. However, in one patient we have identified heart pathology, while the other had tracheal stenosis, requiring tracheostomy. Patients with pronounced dwarfism, skeletal anomalies and other specific syndromes (such as tracheal stenosis and heart anomalies) have to undergo genetic testing in order to exclude syndromes of acromelic dysplasia.