Gene Mutations

On Sunday, April 28, a team of researchers receive the 2019 Human Growth Award at the Pediatric Endocrine Society’s Annual Meeting for their abstract, entitled “Clinical Characterization and Trial of Growth Hormone in Patients with Aggrecan Deficiency: 6 Month Data,” and present this at the PES Presidential Poster Session.

Eirene Alexadrou, M.D., a fellow at Cincinnati Children’s Hospital Medical Center, accept the award and honorarium, while ongoing research is underway. This study start in 2017, with the objective of characterizing the phenotypic spectrum and response to a standardized regimen of growth hormone in a small cohort of 10 patients and their families.

The current abstract now describes six children enroll in a prospective standardize trial of growth hormone therapy. After six months of treatment, the children have increase their height SDS by an average of 0.46, the equivalent of a mean increase height velocity of 9.5 centimeters each year.

The researchers are now performing an in-depth look at joint effects, examining special MRIs of the knees. They found that two of the children had a problem with their knee cartilage called osteochondritis dissecans. They had not yet present with clinical symptoms. The researchers hope that early intervention with physical therapy can help prevent significant joint disease in the future.
Providing growth hormone therapy to children with ACAN gene mutations; which is relatively new in the field of pediatric endocrinology,” notes Dr. Dauber. “Previously, the assumption was that this was just short stature. They’ll continue to diagnose ACAN mutations in a clinical setting; also work with families to reduce the risk of complications; so such as joint problems or early-onset arthritis, which may co-occur with this gene mutation.

Confirm through genetic tests

Her family history reveal clues to an ACAN mutation; which was later confirm through genetic tests. Her mom, M, stands 4’8; her grandmother is 4’9. So her great grandmother was short and her great, great grandfather was 5’1. Short stature and joint problems run in the family. Once mention they had osteochondritis dissecans and a hip replacement; hence they provide a textbook case study for carrying the ACAN mutation.
After the appointment, M share the news with her mother about the possibility of having aggrecan deficiency. After taking genetic tests, M, her mother and M’s daughter learn they all have the ACAN mutation; hence enroll in the study that Dr. Dauber is guiding. Suddenly, it all made sense. After examining family photos; so they trace the ACAN mutation back through four generations.
They could tell what relatives had an alter copy of the ACAN gene. M had it, while her two sisters did not. M’s mother was an only child, so they didn’t have aunts or uncles to compare her mother’s height to; but M’s grandmother was short, while her grandmother’s brother was average height. Although her mother’s family was from Germany; they learn that there is no specific ancestry associate with this mutation.
M and her daughter are happy to be part of this study, which they will participate in for the next few years. M’s mother is also glad to participate. They made a different choice, decades ago, to reject hormone treatment when it was offer to her for undiagnose short stature, but she’s sharing genetic clues, which may influence treatment options for her granddaughter and for her family’s next generation.