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

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

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.

Full Text

Restricted Access

About the authors

Tatyana V. Markova

Research Centre for Medical Genetics

Author for correspondence.
Email: markova@med-gen.ru
ORCID iD: 0000-0002-2672-6294

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

Russian Federation, Moscow

Vladimir M. Kenis

The Turner Scientific Research Institute for Children’s Orthopedics

Email: kenis@mail.ru
ORCID iD: 0000-0002-7651-8485
SPIN-code: 5597-8832
Scopus Author ID: 341189
http://www.rosturner.ru/kl4.htm

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

Russian Federation, Saint-Petersburg

Evgenii V. Melchenko

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

Email: emelchenko@gmail.com

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

Russian Federation, Saint Petersburg

Nina A. Demina

Research Centre for Medical Genetics

Email: ndemina47@mail.ru
ORCID iD: 0000-0003-0724-9004

MD, clinical geneticist, Honored Physician of Russia

Russian Federation, Москва

Polina Gundorova

Research Centre for Medical Genetics

Email: markova@med-gen.ru
ORCID iD: 0000-0001-8703-7997

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

Russian Federation, Moscow

Tatyana S. Nagornova

Research Centre for Medical Genetics

Email: t.korotkaya90@gmail.com
ORCID iD: 0000-0003-4527-4518

MD, clinical geneticist, Laboratory of Selective Screening

Russian Federation, Moscow

Elena L. Dadali

Research Centre for Medical Genetics

Email: markova@med-gen.ru

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

Russian Federation, Moscow

References

  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.

Supplementary files

Supplementary Files
Action
1. Figure: 1. Photo of probands: a - appearance of proband 1; b - appearance of proband 2

Download (148KB)
2. Figure: 2. Photo of proband brushes: a - proband brushes 1; b - proband 2 brushes

Download (155KB)
3. Figure: 3. Magnetic resonance imaging of the brain and spinal cord of the proband 1: 1 - partial hypoplasia of the corpus callosum; 2 - hypoplasia (delayed ossification) of the odontoid process C2

Download (90KB)
4. Figure: 4. Radiograph of hands in frontal projection of proband 1, age - 4 years: 1 - shortened wide phalanges of the fingers; 2 - pseudoepiphyses of the main phalanges of the first fingers; 3 - pseudoepiphyses of the second metacarpal bones

Download (61KB)
5. Figure: 5. X-ray of the hip and knee joints of the proband 1: 1 - dysplastic changes in the acetabulum; 2 - coxa valga; 3 - thin diaphysis of the femur; 4 - hypertubulation of the femur

Download (98KB)
6. Figure: 6. X-ray of the thoracic and lumbar spine in the lateral projection of the proband 1: 1 - hypoplasia of the Th12 vertebral body at the apex of kyphosis; 2 - uneven endplates of the vertebral bodies

Download (66KB)
7. Figure: 7. X-ray of the skull and cervical spine in the lateral projection of the proband 1: 1 - reduction of the facial skull in comparison with the brain; 2 - hypoplasia of the odontoid process C2; 3 - platisponyly

Download (50KB)
8. Figure: 8. X-ray of the hands in frontal projection of proband 2, age - 14 years: 1 - shortened wide phalanges of the fingers; 2 - wide bases (epimetaphysis) of the metacarpal bones

Download (79KB)
9. Figure: 9. X-ray of the hip and knee joints of the proband 2: 1 - dysplastic changes in the acetabulum, narrowing of the joint space; 2 - dystrophic changes and secondary deformity of the proximal femur; 3 - projection narrowing of the obturator openings as an indicator of pelvic inclination

Download (90KB)
10. Figure: 10. Radiograph of the lower extremities in the direct projection of the proband 2: 1 - thin diaphysis of the femur; 2 - hypertubulation of the femur and tibia; 3 - thin diaphysis of the tibia

Download (92KB)
11. Figure: 11. X-ray of the spine in the lateral projection of the proband 1: 1 - unevenness of the endplates of the vertebral bodies; 2 - wedge-shaped deformity of the L1 vertebral body at the apex of kyphosis

Download (68KB)
12. Figure: 12. Radiographs of the cervical spine in the lateral projection of proband 2: a - in the middle position - hypoplasia of the odontoid process C2 (black arrow), an increase in the index of deficit of the height of the odontoid process up to 9 mm (white arrow); b - with head tilted forward - C1 – C2 instability (atlantodental distance - 8 mm, white arrow)

Download (125KB)

Copyright (c) 2021 Markova T.V., Kenis V.M., Melchenko E.V., Demina N.A., Gundorova P., Nagornova T.S., Dadali E.L.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies