Clinical and genetic characteristics and orthopedic manifestations of the Saul–Wilson syndrome in two Russian patients

Tatyana V. Markova; Vladimir M. Kenis; Evgenii V. Melchenko; Nina A. Demina; Polina Gundorova; Tatyana S. Nagornova; Elena L. Dadali

doi:10.17816/PTORS33826

Pediatric Traumatology, Orthopaedics and Reconstructive Surgery ›› 2020, Vol. 8 ›› Issue (4) : 451 -460. DOI: 10.17816/PTORS33826

Clinical cases

research-article

Clinical and genetic characteristics and orthopedic manifestations of the Saul–Wilson syndrome in two Russian patients

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Research Centre for Medical Genetics

The Turner Scientific Research Institute for Children’s Orthopedics

H. Turner National Medical Research Centre for Children’s Orthopedics and Trauma Surgery

MD, PhD, clinical geneticist, Diagnostic Сentre. Research Centre for Medical Genetics

MD, PhD, D.Sc., Deputy Director for Development and International Relations, Head of the Department of Foot Pathology, Neuroorthopedics and Systemic Diseases

MD, PhD, orthopedic surgeon, Research Associate, Department of Foot Pathology, Neuroorthopedics and Systemic Diseases

MD, clinical geneticist, Honored Physician of Russia

PhD in Biology, Senior Research Associate, Laboratory of DNA Diagnostics

MD, clinical geneticist, Laboratory of Selective Screening

MD, PhD, DSci, Professor, Head of Department of Diagnostics

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Abstract

Background. Saul–Wilson syndrome (SWS, microcephalic osteodysplastic dysplasia) is a rare genetic variant of skeletal dysplasia and is determined based on the modern classification for “thin bone dysplasias.” To date, 16 patients with SWS from different countries have been identified.

Clinical cases. We presented the first description of the clinical and genetic characteristics of two Russian patients with SWS and compared them with published data. The main clinical manifestations of SWS are characterized by a combination of nanism and pathology of long tubular bones, spine, and eyes. Changes in the phenotype of patients in different age groups were analyzed.

Discussion. In the analysis of the clinical manifestations of the observed patients and patients described in the literature, typical dysmorphic features of the face and radiographic data help in the diagnosis of SWS upon clinical examination. In the majority of the described patients, the nucleotide substitution c.1546G>A is the major mutation in the gene responsible for SWS, which leads to the replacement of the amino acid Gly516Arg in the protein molecule.

Conclusion. Based on the identified specific features of the phenotype of patients with SWS and the presence of a major mutation in the COG4 gene, a priority analysis of gene mutations is necessary. Orthopedic manifestations of SWS can lead to life-threatening conditions (cervical spine instability) and motor limitations (progressive osteoarthritis) and thus should be monitored dynamically.

Keywords

clinical case / Saul–Wilson syndrome / skeletal dysplasia / COG4 gene / major mutation

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Tatyana V. Markova, Vladimir M. Kenis, Evgenii V. Melchenko, Nina A. Demina, Polina Gundorova, Tatyana S. Nagornova, Elena L. Dadali. Clinical and genetic characteristics and orthopedic manifestations of the Saul–Wilson syndrome in two Russian patients. Pediatric Traumatology, Orthopaedics and Reconstructive Surgery, 2020, 8(4): 451-460 DOI:10.17816/PTORS33826

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References

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[1]	Saul RA. Unknown cases. Proc Greenwood Genet Center. 1982;1:102-103.

[2]	Saul RA, Wilson WG. A ‘new’ skeletal dysplasia in two unrelated boys. Am J Med Genet. 1990;35(3):388-393. https://doi.org/10.1002/ajmg.1320350315.

[3]	Hersh JH, Joyce MR, Spranger J, et al. Microcephalic osteodysplastic dysplasia. Am J Med Genet. 1994;51(3):194-199. https://doi.org/10.1002/ajmg. 1320510304.

[4]	Ferreira CR, Xia ZJ, Clement A, et al. A recurrent de novo heterozygous COG4 substitution leads to Saul-Wilson syndrome, disrupted vesicular trafficking, and altered proteoglycan glycosylation. Am J Hum Genet. 2018;103(4):553-567. https://doi.org/10.1016/ j.ajhg.2018.09.003.

[5]	Ungar D, Oka T, Brittle EE, et al. Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function. J Cell Biol. 2002;157(3):405-415. https://doi.org/10.1083/jcb.200202016.

[6]	Reynders E, Foulquier F, Teles EL, et al. Golgi function and dysfunction in the first COG4-deficient CDG type II patient. Hum Molec Genet. 2009;18(17):3244-3256. https://doi.org/10.1093/hmg/ddp262.

[7]	Ferreira CR, Zein WM, Huryn LA, et al. Defining the clinical phenotype of Saul-Wilson syndrome. Genet Med. 2020;22(5):857-866. https://doi.org/10.1038/s41436-019-0737-1.

[8]	Warman ML, Cormier-Daire V, Hall C, et al. Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A. 2011 May;155(5):943-968. https://doi.org/10.1002/ajmg.a.33909.

[9]	Bonafe L, Cormier-Daire V, Hall C, et al. Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet A. 2015;167A(12):2869-2892. https://doi.org/10.1002/ajmg.a.37365.

[10]	Hall JG, Flora C, Scott CI, et al. Majewski osteodysplastic primordial dwarfism type II (MOPD II): Natural history and clinical findings. Am J Med Genet A. 2004;130A(1):55-72. https://doi.org/10.1002/ajmg.a.30203.

[11]	Bober MB, Jackson AP. Microcephalic osteodysplastic primordial dwarfism, type II: A clinical review. Curr Osteoporos Rep. 2017;15(2):61-69. https://doi.org/10.1007/s11914-017-0348-1.

[12]	Mortier GR, Cohn DH, Cormier-Daire V, et al. Nosology and classification of genetic skeletal disorders: 2019 revision. Am J Med Genet A. 2019;179(12):2393-2419. https://doi.org/10.1002/ajmg.a.61366.