Structural autonomic disorders (producing structural damage to the autonomic nervous system or autonomic centers) are far less common than functional autonomic disorders (reflected in abnormal function of a fundamentally normal autonomic nervous system) in children and teenagers. This article focuses on this uncommon first group in the pediatric clinic. These disorders are grouped into 2 main categories: those characterized by hypoventilation and those that feature an autonomic neuropathy.
Key points
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Several disorders present with autonomic dysregulation and aberrant respiration. These include: familial dysautonomia, ROHHAD syndrome, congenital central hypoventilation, Rett syndrome and Prader Willie.
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Fabry disease is an x-linked disorder that can affect males as well as females. Pain is typically the first symptom. Fabry disease is often under diagnosed early in life and in females due to the nonspecific symptoms.
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There are 5 types of hereditary sensory and autonomic neuropathies (HSAN). HSAN II-V present in infancy or childhood and are autosomal recessive. HSAN I is autosomal dominant, with presentation mainly in adults and a few in adolescents.
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HSAN III (familial dysautonomia) affects mainly individuals of Ashkenazi or Eastern European Jewish descent. It is diagnosed by genetic testing. Early symptoms include poor feeding, oropharyngeal inoordination, decreased pain and temperature sensation, orthostatic hypotension, etc. Acquired autonomic ganglionopathies have antibodies to the ganglionic acetylcholine receptor, blocking the transmission in the sympathetic and parasympathetic branches, and present with moderate to severe orthostatic hypotension and absent axon reflexes.
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The autoimmune autonomic neuropathies affect the distal nerve endings, presenting with chronic pain starting usually in the feet. They can also develop gastrointestinal, urologic and cardiovascular symptoms.
Structural autonomic disorders (producing structural damage to the autonomic nervous system or autonomic centers) are far less common than functional autonomic disorders (reflected in abnormal function of a fundamentally normal autonomic nervous system) in children and teenagers. This article focuses on this uncommon first group in the pediatric clinic. These disorders are grouped into 2 main categories: those characterized by hypoventilation and those that feature an autonomic neuropathy.
Disorders of hypoventilation and autonomic dysregulation
Several disorders harbor both aberrant respiratory control and autonomic regulation, including familial dysautonomia (FD), rapid onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome, congenital central hypoventilation syndrome (CCHS), Rett syndrome, and Prader-Willi syndrome (PWS). Two disorders present very early in life, CCHS and ROHHAD syndrome. The first is fairly well understood, most often due to a specific genetic mutation, whereas ROHHAD is currently diagnosed based on clinical presentation, with no clearly established pathophysiology. This article also briefly covers Rett syndrome and PWS to aid with the consideration of differential diagnosis ( Table 1 ). Because an autonomic neuropathy dominates the pathophysiology of FD, it will be discussed in the second group.
| CCHS | ROHHAD | Rett Syndrome | PWS | |
|---|---|---|---|---|
| Usual onset of disease | Usually birth, but can be later | ∼1.5–9 y | 6–18 mo | At birth |
| Onset of breathing disorder | Birth | Variable | 3–5 y of age | After 1 y of age |
| Obesity | No | Yes | No | Yes, starts between 12 mo and 6 y of age |
| Genetic mutation | PHOX 2 B | Unknown | MECP2 | Mutation in chromosome 15 |
| Autonomic disorder | Fainting, ↓HF-HRV, OH | ↑LF and LF/HF | ↓LF meal response |
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