ESPE Abstracts (2015) 84 P-1-80

Good Clinical Response to the Growth Hormone Therapy in the Patient with Familiar Short Stature Caused by Novel p.Val478Serfs*14 Mutation in ACAN Gene and Isolated Growth Hormone Deficiency

Stepanka Pruhova, Lenka Dusatkova, Petra Dusatkova, Dana Zemkova & Jan Lebl


Second Faculty of Medicine, Department of Paediatrics, Charles University in Prague, University Hospital Motol, Prague, Czech Republic


Background: Recently a heterozygote mutations in the gene ACAN coding the protein aggrecan has been described as a cause of familiar short starture combined with accelerated bone age. The aggrecan is an extracellular proteoglycan in cartilage of growth plates and plays an important role in biological and biomechanical properties of cartilage.

Objective and hypotheses: To provide a genetic screening of ACAN within the families with familiar short stature and describe the potential effect and risks of growth hormone therapy in this patients.

Method: The direct sequencing of the exon and exon – intron boundaries of ACAN.

Results: Novel heterozygote frameshift mutation p.Val478Serfs*14 has been found in the 10-years-old male proband and his father from the family with familiar short stature inherited by the male line (the father has 155 cm (−3.6 SD), his father −4.3 SD (150 cm), fathers brother −3.6 SD and his son −4.3 SD). The mother of the proband has 162 cm (−0.84 SD). The proband was born as SGA for birth length (2920 g/45 cm in 40 GW, −? SD) without any perinatal problems. At the age of 7 years has been found the slightly lower IGF1 level (−1.59 SD) and lower levels of growth hormone in stimulation tests (maximum peak in clonidine test was 3.54 ug/l and in insulin test 3.05 ug/l in the time of glycaemia 2.5 mmol/l). The MRI scan showed the pituitary area without pathology. The growth hormone treatment was started at the age of 7 years and 4 months with the high −3.7 SD (108 cm) at the dosage 0.028 ug/kg/den. After 3.5 years of treatment the high is −2.5 SD, the growth velocity in 1 year of treatment was 10 cm per year, in 2 and 3 years 8 cm per year. The proband had accelerated bone age of 1.5 year at the age of 6 years and the acceleration is stable on the growth hormone therapy. No adverse events has been detected after 3.5 years of treatment.

Conclusion: This is a first description of a novel mutation in ACAN gene as a cause of familiar short stature in the Czech population. The patient has a combination of isolated growth hormone deficiency and FSS. The reaction to the growth hormone is excellent and the bone age remains stabile accelerated.

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