Table 2.
Clinical phenocopies of human hyperekplexia.
| Phenocopy | Comparisons with human startle |
|---|---|
| ACQUIRED HYPEREKPLEXIA | |
| Sub-acute anti-glycine receptor antibody mediated condition that responds to immunosuppression and plasma exchange (Hutchinson et al., 2008) | Similarities Truncal rigidity, muscle spasms and stimulus induced startle |
| Differences Features not present from early life immunosuppression clearly efficacious. Apnoea attacks not described | |
| PAROXYSMAL EXTREME PAIN DISORDER | |
| Autosomal dominant condition recently shown to be a sodium channelopathy involving SCN9A (previously known as familial rectal pain syndrome; Fertleman et al., 2007) | Similarities Onset in neonatal period or infancy, persists throughout life. Dramatic syncopes with bradycardia and sometimes asystole. |
| Tonic attacks are triggered by factors such as defecation, cold wind, eating, and emotion | |
| Differences Autonomic manifestations predominate initially, with skin flushing in all and harlequin colour change. Later attacks of excruciating deep burning pain often in the rectal, ocular, or jaw | |
| JUMPING FRENCHMEN OF MAINE/LATAH SYNDROME | |
| Culturally bound neuropsychiatric syndromes thought to be an anxiety/somatisation disorder (Meinck, 2006) | Similarities Excessive response to startle |
| Differences Echopraxia (involuntary repetition of another's words or actions) and echolalia (repetitive vocalisations) | |
| STARTLE EPILEPSY | |
| Startle epilepsy is a reflex epileptic seizure precipitated by a sudden stimulus; most patients are young and have infantile cerebral hemiplegia (Meinck, 2006) | Similarities Surprising stimuli induce motor reactions – consciousness can be preserved in seizures |
| Differences Neuro-imaging will almost certainly be abnormal | |
| STIFF PERSON SYNDROME | |
| Progressive axial stiffness and intermittent spasms mainly evoked by unexpected stimuli; associated with auto-antibodies to either gephyrin (Butler et al., 2000) or GAD (Meinck, 2006) | Similarities Stimulus induced hypertonia, startles and falls. Hypertonia can preferentially affect lower-limbs |
| Differences Stiffness/hypertonia is much more prolonged than the paroxysmal attacks seen in hyperekplexia | |
| TOURETTE'S SYNDROME | |
| Motor and vocal tics, associated with an exaggerated startle reflex, behaviour change and stereotypy (Bakker et al., 2006) | Similarities Startle response, symptoms precipitate by stressors |
| Differences Vocalisations and obsessive/compulsive behaviours. Motor tics can be complex and appear semi-purposeful | |
| CRISPONI SYNDROME | |
| An autosomal recessive syndrome initially described in 12 different families in southern Sardinia; caused by mutations in the CRLF1 gene (Crisponi, 1996; Crisponi et al., 2007) | Similarities Evident at birth. Marked muscular contraction of the facial muscles in response to tactile stimuli or during crying, contractions slowly disappear as infant calms. Generalised seizures (albeit rare) and mild psychomotor delay in some. Low GABA levels in CSF have been described |
| Differences Abundant salivation simulating a tetanic spasm. Neck muscle hypertonia. Facial anomalies (large face, chubby cheeks, broad nose with anteverted nostrils and long philtrum). Bilateral camptodactyly. Hyperthermia | |
| SYMPTOMATIC STARTLE AND MYOCLONUS | |
| Neuropsychiatric – anxiety states including generalised anxiety disorder, post traumatic stress disorder Cerebral – Children with cerebral palsy, post-traumatic or hypoxic encephalopathy, para neoplastic syndromes Brainstem – particularly pontine patholog yeg Multiple system atrophy (Bakker et al., 2006) | Similarities Symptoms will be exaggerated by stressors. Stimulus sensitive (e.g. touch) can be seen following hypoxic brain injury. Children with cerebral palsy may have a positive nose-tap test |
| Differences Acquired cause often clear, for example late adult onset of multi system atrophy. Hypertonia not a feature of anxiety syndromes | |