Alacrima is the earliest and most consistent
clinical sign of Allgrove syndrome (tearless crying) and may lead to severe
keratopathy and corneal ulcerations. However, a hypoglycemic seizure is the
most common initial presentation, and unrecognized adrenal crisis is still
the leading cause of death in this population. Hyperpigmentation of the
skin, developmental delay, seizures (not hypoglycemic), dysphagia
(achalasia), hypernasal speech (secondary to velopharyngeal incompetence),
and microcephaly are frequent findings. The face often has been described as
long and thin, with a long philtrum, narrow upper lip, and down-turned
mouth. Even in the absence of dysphagia, almost all patients show some
degree of esophageal dysmotility. Megaesophagus is a potential complication.
A history of vomiting, reflux, and dysphagia is frequent and may be
responsible for failure to thrive. Autonomic dysfunction presents with
abnormal sweating, abnormal pupillary reflexes with anisocoria, and poor
heart rate variability with postural hypotension. Other neurologic
manifestations may include polyneuropathy with sensory and motor components,
hyperreflexia, ataxia, muscle weakness parkinsonism (in adults), impaired
visual evoked potentials, and mild mental retardation. Bulbospinal
amyotrophy has been described in several patients. Because autonomic
dysfunction and amyotrophy both are common, some researchers have suggested
that autonomic dysfunction and amyotrophy both be added to the eponym,
making it a AAAAA (5A) instead of AAA (3A) syndrome. Hyperkeratosis
palmoplantaris has been found in many affected individuals. Abdominal CT may
reveal atrophy of the adrenal glands. Autopsy in one patient showed gross
atrophy of the zona fasciculata and reticularis of the adrenals, whereas the
zona glomerulosa was normal.