Most WS1 patients (>60%) have been shown to exhibit neurological symptoms at a mean age of 40 years (range 5–44 years)
[5], but in some cases, onset is earlier
[9][28]. De Heredia et al. found the onset of neurological complications at the mean age of 23 years, with two peaks of greater frequency, one at 13 years and the other at 30 years
[7]. Cerebellar ataxia of the trunk is the most common manifestation (45%), and a neurological counseling one or two times a year is recommended
[11]. Other neurological abnormalities are peripheral neuropathy (39%), cognitive impairment (32%), epilepsy (26%), and lastly, dysarthria, dysphagia, and nystagmus (10%)
[11]. Severe complications, such as aspiration pneumonia, can be prevented by swallowing therapy. Esophageal dilatation and esophagomyotomy are useful in some cases. Neurological symptoms, such as loss of the gag reflex, decreased ability to taste and smell, orthostatic hypotension, anhidrosis, hypohidrosis or hyperhidrosis, constipation, gastroparesis, hypothermia, or hyperpyrexia, may often be reported
[11]. Atrophy of the brain, cerebellum, and brainstem are abnormalities found by nuclear magnetic resonance imaging (MRI) in 54% of WS1 patients
[11]. Respiratory failure or dysphagia are common causes of mortality
[5][11]. Thus far, the progression of neurological manifestations cannot be slowed down, as there is no therapy. Psychiatric disorders, such as severe depression with suicide attempts, psychosis, sleep abnormalities, verbal impulsivity, and physical aggression, can complicate the clinical picture in WS1 patients. Moreover, a predisposition to psychiatric diseases was found in
WFS1 heterozygotes
[29]. Cognitive performance is generally normal. However, Chaussenot et al. found that 32% of 59 studied WS1 patients had cognitive impairment
[11]. It has been suggested that the smell and sleep alterations can be used as indicators to follow-up WS1 patients with psychiatric manifestations
[30].