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Clinical and Molecular Delineation of Cutis Laxa Syndromes: Paradigms for Elastic Fiber Homeostasis

  • Chapter
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Progress in Heritable Soft Connective Tissue Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1348))

  • The original version of this chapter was revised: The book was inadvertently published with incorrect Chapter title which has been corrected now. The correction to this chapter is available at https://doi.org/10.1007/978-3-030-80614-9_16

Abstract

Cutis laxa (CL) syndromes are a large and heterogeneous group of rare connective tissue disorders that share loose redundant skin as a hallmark clinical feature, which reflects dermal elastic fiber fragmentation. Both acquired and congenital-Mendelian- forms exist. Acquired forms are progressive and often preceded by inflammatory triggers in the skin, but may show systemic elastolysis. Mendelian forms are often pleiotropic in nature and classified upon systemic manifestations and mode of inheritance. Though impaired elastogenesis is a common denominator in all Mendelian forms of CL, the underlying gene defects are diverse and affect structural components of the elastic fiber or impair metabolic pathways interfering with cellular trafficking, proline synthesis, or mitochondrial functioning. In this chapter we provide a detailed overview of the clinical and molecular characteristics of the different cutis laxa types and review the latest insights on elastic fiber assembly and homeostasis from both human and animal studies.

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Change history

  • 06 January 2022

    The book was inadvertently published with incorrect Chapter title. The title has been corrected in Chapter 13 now.

Abbreviations

AA :

Ascorbic acid

ADAMTS:

a Disintegrin and metalloproteinase with thrombospondin motifs

ADCL :

Autosomal dominant cutis laxa

ALDH :

Aldehyde dehydrogenase

Apo C-III :

Apolipoprotein CIII

ARCL :

Autosomal recessive cutis laxa

ARCL1 :

ARCL Type 1

ARCL2 :

ARCL Type 2

ARCL3 :

ARCL Type 3

ARD :

Aortic root dilatatio

ATS :

Arterial tortuosity syndrome

CDG :

Congenital disorder of glycosylation

CFC :

Cardiofaciocutaneous

CHST14 :

Carbohydrate sulfotransferase 14

CL :

Cutis laxa

CRISPR :

Clustered regularly interspaced short palindromic repeats

DBS :

De Barsy syndrome

DSE :

Dermatan sulfate epimerase

EBP :

Elastin binding proteins

ECM :

Extracellular Matrix

EDS :

Ehlers Danlos syndrome

EGR1 :

Early growth response 1

ELN :

Elastin

ER :

Endoplasmic reticulum

FLN :

Fibulin

GLUT10 :

Glucose transporter 10

GO :

Geroderma osteodysplastica

HGPS :

Hutchinson-Gilford progeria syndrome

IUGR :

Intra-uterine growth retardation

KD :

Knockdown

KI :

Knockin

KO :

Knockout

LAP :

Latency-associated protein

LOX :

Lysyl oxidase

LTBP :

Latent transforming growth factor β

MACS :

Macrocephaly, alopecia, cutis laxa and scoliosis

MD :

Menkes disease

MFS :

Marfan syndrome

MGUS :

Monoclonal gammopathy of undetermined significance

MO :

Morpholino

NGS :

Next-generation sequencing

OHS :

Occipital horn syndrome

P5CSΔ1 :

Pyrroline-5-carboxylate synthase enzyme

PAR1 :

Protease activating factor–1

PLOD1 :

Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase

PYCR1 :

Pyrroline-5-carboxylate reductase 1

SCARF :

Skeletal abnormalities, cutis laxa, craniostenosis, ambiguous genitalia, retardation and facial abnormalities

TALDO :

Transaldolase

TEM :

Transmission electron microscopy

TIEF :

Transferrin-isoelectric focusing analysis

VSMC :

Vascular smooth muscle cell

VUR :

Vesicourethral reflux

VUS :

Variants of unknown significance

UPR :

Unfolded protein response

WRS :

Wiedeman-Rautenstrauch syndrome

WSS :

Wrinkly skin syndrome

XRCL :

X-linked recessive cutis laxa

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Ethical Statement

This work is supported by the Special Research Fund, Flanders of Ghent University (Belgium, grant 01N04516C to B.C.), the Research Foundation Flanders (project G035620N to B.C.) and the European Academy of Dermatovenereology (Switzerland, EADV project PPRC-2018-50 to B.C.). B.C. is a senior clinical investigator of the Research Foundation Flanders. The Ghent University Hospital is a member of the European Reference Network for skin disorders (ERN-skin). Clinical pictures are published after written informed consent of the patient or, in case of minors, their legal guardian. Previously published pictures are reprinted with permission. Clinical pictures were not masked due to scientific and educational reasons, allowing for better patient recognition and care.

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Authors and Affiliations

  1. Center for Medical Genetics Ghent, Department of Dermatology, Department of Biomolecular Medicine, Ghent University Hospital, Ghent University, Ghent, Belgium

    Aude Beyens

  2. Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium

    Lore Pottie & Patrick Sips

  3. Department of Biomolecular Medicine, Ghent University, Ghent, Belgium

    Lore Pottie & Patrick Sips

  4. Center for Medical Genetics Ghent, Department of Biomolecular Medicine, Ghent University Hospital, Ghent University, Ghent, Belgium

    Bert Callewaert

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  1. Aude Beyens
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  2. Lore Pottie
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  3. Patrick Sips
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  4. Bert Callewaert
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Correspondence to Bert Callewaert .

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Editors and Affiliations

  1. Department of Pathology, College of Veterinary Medicine, and Department of Basic Sciences, AU/UGA Medical Partnership, The University of Georgia, Athens, GA, USA

    Jaroslava Halper

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Beyens, A., Pottie, L., Sips, P., Callewaert, B. (2021). Clinical and Molecular Delineation of Cutis Laxa Syndromes: Paradigms for Elastic Fiber Homeostasis . In: Halper, J. (eds) Progress in Heritable Soft Connective Tissue Diseases. Advances in Experimental Medicine and Biology, vol 1348. Springer, Cham. https://doi.org/10.1007/978-3-030-80614-9_13

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