Endocrine Abstracts

JOINT2690

Introduction: 3MSyndrome is autosomal recessive inherited dwarfism, characterized by pre and postnatal growth retardation. 3Msyndrome develops as a result of biallelic loss of function mutations in cullin7(CUL7), obscurin-like1(OBSL1), and coiled-coil domain- containing protein8 genes(CCDC8) are responsible for p53 dysfunction, growth hormone(GH) and/or IGF1 resistance. The aim of this study is to evaluate the the growth hormone(GH) axis and response to GH treatment in 3M syndrome patients.

Methods: Medical records of eight patients followed up with short stature in our Pediatric Endocrinology department and diagnosed with 3M syndrome based on the results of genetic tests, between 2015 and 2024 were recorded. Serum basal levels of IGF1 were determined using immunoradiometric assays. All patients underwent a growth hormone stimulation test(GHST) were performed with levodopa and clonidine. Insulin-like growth factor(IGF) generation test was performed on those with sufficient GHST results.

Results: A total of 8 patients(four males and four males)from 7 families with 4,94(3,5–11,7) years median age at the time the GH treatment started were included in this study and were followed for one to eight years. Out of 7 families, six were consanguineous, one unrelated. All of the patients were born at term. The mean SDSs of birth weight and length of the patients were –3,15±1, −4,0±0.60, respectively. The median height SDS at admission was −4,30((−7,27)- (−2,75))SDS, and the median midparenteral height SDS was –0,76SDS((−1,68)- (-0,27)). The partial deficiency was detected in three cases, severe deficiency in one case. IGF generation test was performed in three cases and all were responsive. Despite described growth hormone (GH) insensitivity in 3M syndrome, all our patients either with GH deficiency or with normal GH levels were treated with GH. The percentile improved in all patients. The median annual growth velocity in the first year of treatment (6,1 cm/year) and in last follow up (5,85 cm/year) was higher compared to pre- treatment levels(5,3 cm/year) (p:0,017). The final height SDS of two cases were – 4,3 SDS and – 4,11SDS because of closure of the growth plates.

Discussion: Although the annual height growth rates of patients under treatment are insufficient, their final heights have been found to be higher compared to those of patients who were followed without treatment in the literatüre. Even the absence of worsening in height SDS in patients receiving growth hormone may be considered as a good response to treatment. It is difficult to reach a conclusion about the efficiency of GH treatment in 3M syndrome patients.