Clin Auton Res (2002) 12 (Suppl 1) : I/1© Steinkopff Verlag 2002

Felicia B. Axelrod Genetic disorders as models to understand autonomic dysfunction

Introduction

At the 12th International Symposium of the AmericanAutonomic Society in October 2001 in Palm Springs,California, a focused satellite symposium was dedicatedto Genetic Disorders as Models to Understand Auto-nomic Dysfunction. The impetus for choosing this sub-ject for in-depth discussion was the recent identificationof the mutations causing familial dysautonomia, themost common of the genetic disorders associated withautonomic and sensory dysfunction. This monograph isa compilation of the lectures given at that symposium.

The complexities of the autonomic nervous systemand its intimate relationship with sensory function areespecially well illustrated in the diversity of a group ofgenetic disorders known as Hereditary Sensory andAutonomic Neuropathies (HSAN). Each HSAN consistsof a genetically and pathologically homogenous popula-tion producing a number of excellent models to furtherour knowledge regarding development and mechanismsof the autonomic and sensory nervous systems.

All of the HSAN disorders affect autonomic and sen-sory function, but there are definite phenotypic differ-ences that are believed secondary to specific genotypicdifferences.Although each disorder affects developmentof the autonomic and sensory nervous systems, the ex-tent of impairment and subsequent manifestations de-pend upon the specific genetic abnormality. This is theera of the genome so it is quite appropriate that auto-nomic researchers also look more closely at the geneticmodels causing autonomic dysfunction to provide in-sight into understanding development of the autonomicnervous system and the reason for frequent associatedsensory perturbations.

Because each HSAN provides a genetically homoge-nous population, as a group they can provide insight, as

well as speculation, into the pathophysiology of adultonset autonomic disorders in which there is neuronaldegeneration.In addition their defined populations lendthemselves to studies and treatment trials. At this pointseven such disorders have been recognized (Table 1) andspecific genetic mutations have been identified for threeof these disorders.

This monograph focuses on the two most commonHSAN disorders, familial dysautonomia (FD) and con-genital insensitivity to pain with anhidrosis (CIPA).These two disorders are also known as HSAN type IIIand type IV,respectively.The clinical manifestations, therecent advances in genetics and the specific autonomicand sensory tests that can be used to differentiate thedisorders are discussed by individuals who are recog-nized experts in the area.

It is also appropriate to acknowledge the vision andsupport of the Dysautonomia Foundation in preparingthis monograph. For almost 50 years, the DysautonomiaFoundation has provided financial and motivational re-sources for clinical and basic research in this field.Through grants they have supported the DysautonomiaTreatment and Evaluation Center at New York UniversityMedical Center. This facility has facilitated centraliza-tion of care leading to improved morbidity and mortal-ity for individuals affected with FD. The Center has alsobeen able to conduct retrospective and prospectivestudies leading to analysis and trials of new treatments,as well as clinical research to further understand patho-physiology. In addition the Foundation has sponsoredgenetic research at the laboratories of Drs. Gusella andSlaugenhaupt at Massachusetts General Hospital fromwhich genetic discoveries and extensive background in-formation fostered initial haplotype reports and even-tual specific identification of the gene.We now acknowl-edge their support in this venture as we recognize thatmuch of the work presented in this monograph is alsoan expression of their achievements.