ESPE Abstracts (2022) 95 P1-420

ESPE2022 Poster Category 1 Bone, Growth Plate and Mineral Metabolism (46 abstracts)

Skeletal phenotype in patients with the monogenic Mulibrey nanism disorder

Susann Karlberg 1,2,3 , Sanna Toiviainen-Salo 1,2,3 , Marita Lipsanen-Nyman 1 & Outi Mäkitie 1,2,3


1Children’s Hospital and Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 2Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 3Folkhälsan Research Center, Helsinki, Finland

Background: Mulibrey nanism (MUL) is a monogenic growth disorder with typical craniofacial features, perimyocardial heart disease, infertility and predisposition to tumors. MUL is caused by mutations in the TRIM37 gene encoding TRIM37 protein possessing E3 ubiquitin-ligase activity.

Objective and hypotheses: MUL patients have pre- and postnatal growth failure with an average birth length SDS of -3.1 and birth weight SDS of -2.8. Clinically, patients are gracile with relative macrocephaly, thin extremities and narrow shoulders. Facial features include triangular face with high, broad forehead and low nasal bridge. Fibrous dysplasia of long bones has been observed in up to 25% of the patients but the full spectrum of skeletal features remains unknown. We conducted a cross-sectional study in order to further clarify the skeletal phenotype.

Methods: The study included altogether 33 patients with MUl, aged 4.5-48 years (14 females and 19 males, median age 16.7 years) undergoing routine check-ups at the Children’s Hospital. Radiographs of the long bones and spine were assessed for skeletal features. Hospital records were reviewed for clinical characteristics, bone health and fractures.

Results: Radiographic analysis confirmed significant skeletal abnormalities related to MUL. Skeletal changes were present in all patients. The vertebral bodies were anomalous in all patients with ceased growth. The vertebral bodies were high, with an increased ratio between the vertical diameter and the sagittal diameter. Vertebral endplates were concave. The long bones were slender. The metaphyses were broad in comparison with the narrow diaphyses. Bowing of long bones was observed in all patients. Bowing of the radius was most frequent, observed in 31/33 (94%) of patients, followed by bowing of the fibula in 25/33 patients (76%). The cortices of the long bones were thick in all 33 patients and the medullary cavities were narrow. Cortical thickness was most pronounced in the femur and radius. Radiographic changes of fibrous dysplasia were found in 19/33 patients (58%); changes were monostotic in 63% and polyostotic in 37%. Fibrous dysplasia was equally frequent in females and males. Altogether 14/33 patients (42%) had a history of fractures.

Conclusions: Our study confirms that in addition to short stature, patients with MUL have a specific skeletal dysplasia. The characteristic features include high vertebral bodies, slender and curved long bones with thick cortex and narrow medullary cavity, and a high prevalence of fibrous dysplasia and fractures. Our findings suggest an important role for TRIM37 in cellular functions governing skeletal homeostasis.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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