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A Dysmorphometric Analysis to Investigate Facial Phenotypic Signatures as a Foundation for Non-invasive Monitoring of Lysosomal Storage Disorders

  • Research Report
  • Chapter
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JIMD Reports - Case and Research Reports, 2012/5

Part of the book series: JIMD Reports ((JIMD,volume 8))

Abstract

Background: Some lysosomal storage disorders (LSDs), including Muccopolysaccharidosis type 1 (MPSI), are associated with characteristic facies. Methods such as three-dimensional (3D) facial scanning and geometric morphometric techniques can potentially generate detailed objective descriptions of these facial phenotypes. This approach can facilitate discriminating the inherent overlap in facial phenotypes within these disease spectra, and the non-invasive monitoring of disease progression and treatment.

Methods: 3D facial images of three MPS I-affected individuals and 400 reference subjects (aged 5–25 years) were obtained using a 3dMD camera (Atlanta, Georgia). Images were fitted with an anthropometric mask, comprising a set of spatially dense quasi-landmarks. A statistical face-space was constructed from the reference image set and the MPS I-affected individuals were compared to this face-space utilising an emerging methodology known as dysmorphometrics. This facilitated simultaneous identification of harmonic and discordant facial regions. A relative significant discordance (RSD) score quantified proportional facial discordance for a given individual, whilst a root-mean-squared-error (RMSE) score measured the degree of facial discordance providing a severity measure.

Results: A consistent facial pattern, with differential severities, primarily affecting the frontal, nasal, infraorbital and cheek regions, was detected in all three individuals. As expected, there was greater discordance (RMSE, RSD) with clinically severe MPS I when compared to attenuated disease.

Conclusions: Objective detection and localisation of MPS I facial characteristics was achieved, and severity scores were attributed. This spatially dense dysmorphometric facial phenotyping technique has the potential to be used for non-invasive treatment monitoring and as a discriminatory tool.

Competing interests: None declared

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Abbreviations

2D:

Two-dimensional

3D:

Three-dimensional

AM:

Anthropometric mask

BMT:

Bone marrow transplantation

EMA:

European medicines agency

ERT:

Enzyme replacement therapy

IDUA:

α-L-iduronidase

LSDs:

Lysosomal storage disorders

MPS I:

Muccopolysaccharidosis type I

MPS IH:

Muccopolysaccharidosis type I, Hurler Syndrome

MPS IHS:

Muccopolysaccharidosis type I, Hurler-Scheie Syndrome

MPS IS:

Muccopolysaccharidosis type I, Scheie Syndrome

NE:

Normal equivalent

PCA:

Principal component analysis

PCs:

Principal components

RMSE:

Root-mean-squared-error

RSD:

Relative significant discordance

SD:

Standard deviation

SMAS:

Submuscular aponeurotic system

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Acknowledgements

The authors would like to thank all participants for their permission to use their images, everyone involved with the 11th International Symposium on MPS and Related Diseases in Adelaide, David Oliver and his colleagues from The Australian MPS and related diseases and Genzyme Australia. This work is supported by the Princess Margaret Hospital (PMH) Foundation in Perth, Western Australia, and has been approved by the PMH Ethics Committee (PMHHEC: 1801/EP, 1443/EP and 1488/EP). Genzyme provided an unrestricted educational grant and had no role in the interpretation or analysis of the data or in the decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Genetic Services of Western Australia, Princess Margaret & King Edward Memorial Hospitals, 4th Floor Agnes Walsh House, 374 Bagot Road, Subiaco, WA, 6008, Australia

    Jack Goldblatt & Gareth Baynam

  2. Cranio-Maxillo-Facial Unit, Princess Margaret Hospital for Children, Perth, WA, Australia

    Mark Walters

  3. Medical Imaging Research Centre, Faculty of Engineering, K.U. Leuven, Leuven, Belgium

    Peter Claes

  4. School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia

    Stefanie Kung, Jack Goldblatt, Peter Le Souef & Gareth Baynam

Authors
  1. Stefanie Kung
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  2. Mark Walters
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  3. Peter Claes
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  4. Jack Goldblatt
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  5. Peter Le Souef
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  6. Gareth Baynam
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Corresponding author

Correspondence to Gareth Baynam .

Editor information

Editors and Affiliations

  1. Sektionen für Humangenetik und Klinische, Medizinische Universität Innsbruck, Schöpfstr. 41, Innsbruck, A-6020, Austria

    Johannes Zschocke

  2. , Biological Sciences, Michigan Technological University, Townsend Drive 1400, Houghton, 49931, Michigan, USA

    K Michael Gibson

  3. , Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, United Kingdom

    Garry Brown

  4. Medical Center, Department of Pediatrics, Radboud University Nijmegen, Geert Grooteplein 9, Nijmegen, 6500 HB, Netherlands

    Eva Morava

  5. Heidelberg University Hospital, Center for Child and Adolescent Medicine, Im Neuenheimer Feld 430, Heidelberg, 69120, Germany

    Verena Peters

Additional information

Communicated by: Verena Peters

Appendices

Authors’ Information

GB (MBBS, DCH, FRACP, PhD) Clinical Geneticist at Genetic Services of Western Australia (GSWA), Senior Clinical Lecturer at the School of Paediatrics and Child Health (SPACH), University of Western Australia. MW (MSc), Senior Research Scientist, Cranio-Maxillo-Facial Unit, Princess Margaret Hospital for Children (PMH), developer of facial assessment tools investigating normal and disordered facial growth patterns. PC (PhD), Computer Science Engineer and research expert on cranio-maxillofacial morphometrics, Catholic University of Leuven, Belgium. Winthrop Professor PLS (MBBS, MRCP, FRACP, MD) Head of SPACH and Consultant Physician at the Department of Respiratory Medicine, PMH. JG (AM, MB ChB, MD, FRACP) Clinical Professor at SPACH and Director of Genetic Services and the Familial Cancer Program of WA. SK (BSc Hons), PhD student at SPACH with a background in anatomy and genetics.

Synopsis

Objective 3D facial phenotyping using dysmorphometrics provides prospective avenues for non-invasive treatment monitoring of metabolic conditions.

Authors’ Contributions

SK wrote the manuscript with major input and revisions from all other authors. MW and GB were involved in drafting of the manuscript, while PC, JG and PLS provided valuable critical feedback. PC developed the fundamentals behind the anthropometric mask, the statistical face-space, dysmorphometrics, and the normal equivalent, with conceptual input from MW. PC also provided the facial mapping of the data and constructed the normative facial model of covariance. Finally, he ran the leave-one-out analysis to establish normative reference discordancy statistics. GB and JG provided clinical insight into investigated syndromes, rallied support from the MPS Society and fostered international collaborations. All authors read and approved the final manuscript.

Guarantor

As guarantor for this article, GB accepts full responsibility for this work and conduct of this study, has had access to the data, and controls the decision to publish.

Competing Interests

The authors declare that they have no competing interests.

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Kung, S., Walters, M., Claes, P., Goldblatt, J., Le Souef, P., Baynam, G. (2012). A Dysmorphometric Analysis to Investigate Facial Phenotypic Signatures as a Foundation for Non-invasive Monitoring of Lysosomal Storage Disorders. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Case and Research Reports, 2012/5. JIMD Reports, vol 8. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2012_152

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  • DOI: https://doi.org/10.1007/8904_2012_152

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  • Print ISBN: 978-3-642-33432-0

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