ESPE Abstracts

Background: The reasons for tall stature, defined as a height above the 97. percentile or above 2SD from the mean, are heterogeneous. Besides non-pathogenic forms like familial tall stature or constitutional advance of growth there are pathogenic forms like obesity, growth hormone excess, hyperthyreoidism, precocious puberty or some genetic disorders and syndromes that need to be concerned.

Case Report: We report on a 14 years and 6 months old boy who presented at the outpatient clinic with a tall stature of 192,7cm (above the 99. percentile), a narrow trunk and myopia. In his past medical history it was referred to motor development retardation in early childhood with impaired joint mobility of knees and elbows. Familial tall stature, growth hormone excess and constitutional advance of growth had been excluded by physical examination, family history and laboratory tests. The Marfan-like appearance led to genetic testing in consideration of a syndrome associated to tall stature. In our patient we detected a heterozygous pointmutation c.7201A>C in the fibrillin 2 gene (FBN2), which is classified as a variant of unknown significance class 3 (VUS 3). In silico analysis are ranking this VUS 3 differently. FBN2 is encoding for fibrillin-2, a matrix protein involved in the construction of elastic fibres. Mutations in this gene cause congenital contractural arachnodactyly (CCA; Beals-Hecht syndrome), whose prevalence is unknown. Typical symptoms of CCA are long limbs, narrow body, joint contractures, tall stature, crumpled ears and aortic dilatation. To determine the VUS 3 either as a de novo-mutation or as an autosomal-dominant inherited mutation, the patient´s parents were tested subsequently. In the patient´s mother the same VUS was verified and an adjacent screening of the mother regarding typical symptoms of CCA showed an aortic dilatation, whereas the mother had no tall stature and no myopia.

Results: We found a VUS 3 in the FBN2 gene in our patient and his mother revealing an autosomal dominant inheritance. Both of the affected family members showed clinical signs according to congenital contractural arachnodactyly, so that the correlation between the VUS3 and the described symptoms in our individuals seems to be likely.