Small fiber neuropahty in CdLS
INTRODUCTION: Cornelia de Lange Syndrome (CdLS) is a genetic disease with manifestations in different body systems (gastrointestinal, genitourinary, cardiac, otolaryngologic, ophthalmologic, musculoskeletal, skin, encrodrine, behavioral and neurodevelopmental, with typical facial features and growth alterations).
The manifestations in the neurologic system consist of seizures, intellectual disability and sleep disturbances. The patients present also with symptoms such as increased pain threshold, blotching of the skin, abnormalities of sweating, abnormal reactions to cold and heat, and gastro-intestinal symptoms, suggesting a compromise of the Autonomic Nervous System functions. At this moment, there is not enough evidence to support this.
OBJECTIVES:
To show the compromise of the autonomic nervous system in patients with CdLS.
MATERIAL AND METHODS:
We studied the peripheral and autonomic nervous system in the Neurophysiology lab in a group of 20 patients with CdLS. The test used for the study of the peripheral nervous system were motor and sensory conduction studies. The most sensitive test to study the small fibers is a skin biopsy with axonal marker PGP 9.5 (small sensory skin fibers, gold standard) and laser evoked potentials (Aδ fibers). Unfortunately, this equipment is not available in all the Neurophysiology labs, so we used the following test to study the autonomic nervous system: Heart-rate variability at rest, sympathetic skin response and Sudomotor test for the autonomic nervous system.
RESULTS:
The study of the peripheral nervous system (motor and sensory conduction studies) was normal in all the patients. The study of the heart rate variability at rest was normal as well in all the patients.
The sudomotor test showed a reduction in the sweat glands density in 54.5% of the patients. The sympathetic skin response test showed asymmetrical responses in lower limbs in 40.9% of the patients.
CONCLUSION:
Despite the fact that the most objective tests to study the small fiber nerves are not available in our lab, the abnormalities observed in the studies of the sweat gland density and sympathetic skin response tests suggest damage in the autonomic fibers compatible with small fiber neuropathy, without somatic neuropathy (thick fiber, fast conducting nerves preserved). Further studies are needed to confirm our results.
Conflicts of interest: none.
- REFERENCES;
- Christopher J. Mathias and Sir Roger Bannister. Autonomic Failure. A Textbook of Clinical Disorders of the Autonomic Nervous System. Oxford: Oxford University Press, 1992.
- Ferrer T, Ramos MJ, Pérez-Sales P, Pérez-Jiménez A, Alvarez E. “Sympathetic sudomotor function and aging”. Muscle Nerve 18 (1995): 395-401.
- Low PA and Zimmerman IR. Development of an Autonomic Laboratory. Clinical Autonomic Disorders. Boston: Little, Brown and Co, 1993.
- Kline AD, Moss JF, Selicorni A, Bisgaard AM, Deardorff MA, et al. “Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement”. Nat Rev Genet 19 (2018):649-666.
- Kline AD, Krantz ID, Sommer A, Kliewer M, Jackson LG et al. “Cornelia de Lange Syndrome: Clinical Review, Diagnostic and Scoring Systems, and Anticipatory Guidance”. Am J Med Genet A 143A (2007):1287-96.
CdLS World Conference 219, Germany an Netherlands, Ahrweiler, published on 31 jul. 2019
