SGMS2 in primary osteoporosis with facial nerve palsy

Sandra Pihlström; Sampo Richardt; Kirsi Määttä; Minna Pekkinen; Vesa M Olkkonen; Outi Mäkitie; Riikka E Mäkitie

doi:10.3389/fendo.2023.1224318

SGMS2 in primary osteoporosis with facial nerve palsy

Front Endocrinol (Lausanne). 2023 Oct 11:14:1224318. doi: 10.3389/fendo.2023.1224318. eCollection 2023.

Authors

Sandra Pihlström^{1

2}, Sampo Richardt^{1

2}, Kirsi Määttä^{1

2}, Minna Pekkinen^{1

2

3}, Vesa M Olkkonen^{4

5}, Outi Mäkitie^{1

2

3

6}, Riikka E Mäkitie^{1

2

7}

Affiliations

¹ Folkhälsan Institute of Genetics, Helsinki, Finland.
² Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
³ Children´s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁴ Minerva Foundation Institute for Medical Research, Helsinki, Finland.
⁵ Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁶ Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
⁷ Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Abstract

Pathogenic heterozygous variants in SGMS2 cause a rare monogenic form of osteoporosis known as calvarial doughnut lesions with bone fragility (CDL). The clinical presentations of SGMS2-related bone pathology range from childhood-onset osteoporosis with low bone mineral density and sclerotic doughnut-shaped lesions in the skull to a severe spondylometaphyseal dysplasia with neonatal fractures, long-bone deformities, and short stature. In addition, neurological manifestations occur in some patients. SGMS2 encodes sphingomyelin synthase 2 (SMS2), an enzyme involved in the production of sphingomyelin (SM). This review describes the biochemical structure of SM, SM metabolism, and their molecular actions in skeletal and neural tissue. We postulate how disrupted SM gradient can influence bone formation and how animal models may facilitate a better understanding of SGMS2-related osteoporosis.

Keywords: SGMS2-related osteoporosis; SMS2; bone and neural tissue; sphingolipids; sphingomyelin metabolism.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Child
Facial Nerve* / metabolism
Facial Nerve* / pathology
Humans
Infant, Newborn
Osteoporosis* / complications
Osteoporosis* / pathology
Paralysis
Skull / metabolism
Sphingomyelins / metabolism
Transferases (Other Substituted Phosphate Groups)* / metabolism

Substances

Sphingomyelins
Transferases (Other Substituted Phosphate Groups)
SGMS2 protein, human

Grants and funding

Academy of Finland (318137, 322647), Sigrid Juselius Foundation, Folkhälsan Research Foundation, Foundation for Pediatric Research (190155, 200196), Nylands Nation at University of Helsinki, Sigrid Jusélius stiftelse, Novo Nordisk Foundation (NNF180C0034982), HUS EVO at Helsinki University Hospital (TYH2021221), Finnish ORL–HNS Foundation, Finnish Medical Foundation.