High rate of autonomic neuropathy in Cornelia de Lange Syndrome

M J Pablo; P Pamplona; M Haddad; I Benavente; A Latorre-Pellicer; M Arnedo; L Trujillano; G Bueno-Lozano; L M Kerr; S A Huisman; F J Kaiser; F Ramos; A D Kline; J Pie; B Puisac

doi:10.1186/s13023-021-02082-y

High rate of autonomic neuropathy in Cornelia de Lange Syndrome

Orphanet J Rare Dis. 2021 Oct 30;16(1):458. doi: 10.1186/s13023-021-02082-y.

Authors

M J Pablo^{1

2}, P Pamplona^{1

3}, M Haddad^{1

3}, I Benavente², A Latorre-Pellicer¹, M Arnedo¹, L Trujillano^{1

4}, G Bueno-Lozano^{1

5}, L M Kerr⁶, S A Huisman^{7

8}, F J Kaiser⁹, F Ramos^{1

4}, A D Kline¹⁰, J Pie¹¹, B Puisac¹²

Affiliations

¹ Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain.
² Unit of Neurophysiology, San Jorge University Hospital, Huesca, Spain.
³ Unit of Neurophysiology, Miguel Servet University Hospital, Zaragoza, Spain.
⁴ Unit of Clinical Genetics, Department of Pediatrics, Hospital Clinico Universitario "Lozano Blesa", CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain.
⁵ Department of Pediatrics, Hospital Clinico Universitario "Lozano Blesa", Growth, Exercise, Nutrition and Development (GENUD) Research Group, Zaragoza, Spain.
⁶ Division of Pediatric Neurology, Department of Paediatrics, University of Utah Health, Salt Lake City, UT, USA.
⁷ Department of Pediatrics, Amsterdam UMC, Amsterdam, The Netherlands.
⁸ Prinsenstichting, Purmerend, The Netherlands.
⁹ Institute of Human Genetics, University Hospital Essen University of Duisburg-Essen, Essen, Germany.
¹⁰ Harvey Institute of Human Genetics, Greater Baltimore Medical Center, Baltimore, MD, USA.
¹¹ Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain. juanpie@unizar.es.
¹² Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain. puisac@unizar.es.

Abstract

Background: Cornelia de Lange Syndrome (CdLS) is a rare congenital disorder characterized by typical facial features, growth failure, limb abnormalities, and gastroesophageal dysfunction that may be caused by mutations in several genes that disrupt gene regulation early in development. Symptoms in individuals with CdLS suggest that the peripheral nervous system (PNS) is involved, yet there is little direct evidence.

Method: Somatic nervous system was evaluated by conventional motor and sensory nerve conduction studies and autonomic nervous system by heart rate variability, sympathetic skin response and sudomotor testing. CdLS Clinical Score and genetic studies were also obtained.

Results: Sympathetic skin response and sudomotor test were pathological in 35% and 34% of the individuals with CdLS, respectively. Nevertheless, normal values in large fiber nerve function studies.

Conclusions: Autonomic nervous system (ANS) dysfunction is found in many individuals with Cornelia de Lange Syndrome, and could be related to premature aging.

Keywords: Autonomic neuropathy; CdLS; Cornelia de Lange Syndrome; NIPBL gene; Peripheral neuropathy; Small fiber nerve; Sudomotor test; Sweat gland density.

Publication types

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

MeSH terms

Autonomic Nervous System
Cell Cycle Proteins / genetics
De Lange Syndrome* / genetics
Humans
Mutation / genetics
Phenotype

Substances

Cell Cycle Proteins