Table 1.

Main clinical characteristics. BEAR brainstem evoked acoustic responses, F female, M male, mo month, n/a not applicable, yrs. years

	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6	Patient 7	Patient 8	Patient 9
Gender	F	F	F	M	F	M	M	M	F
Current age	2 yrs	2 yrs	21 mo	7 yrs	7 yrs	6 yrs	22 yrs	26 yrs	29 yrs
Affected siblings	No	No	No	No	No	No	Yes, patient 8	Yes, patient 7	No
Consanguinity	No	No	No	No	No	No	Yes	Yes	No
Age at onset	2 months	First days of life	First days of life	First year of life	Second year of life	13 months	4 years	Second year of life	14 months
Signs/symptoms at onset	No smiling, failure to thrive	No crying, absent visual contact	Abnormal movements, restlessness	Global developmental delay, poor facial expression	Mild motor delay	Abnormal gait	Psychomotor retardation	Mild delay in language acquisition	Abnormal gait, prone to falling
Age at last examination	17 mo	2 yrs.	16 mo	5 yrs	5 yrs	4 yrs.	21 yrs	26 yrs	29 yrs
Axial hypotonia	Yes	Yes, if relaxed. Severe opisthotonus in agitated episodes	Severe	No	No	Mild	No	No	No
Head balance	Suboptimal	Suboptimal at 2 mo, lost at 4 mo	Suboptimal	Suboptimal at three mo	Normal	Normal	Normal	Normal	Normal
Ataxia	No intentional movements	No intentional movements	No	Yes	Mild gait ataxia	Yes	No	No	Head titubation
Pyramidal signs	No	Yes	No	Yes	No	Yes	No	No	Mild pyramidal signs (legs)
Extrapyramidal signs	Yes, choreic movements and opisthotonus	Yes, choreic movements	Yes, choreic movements and opisthotonus	Yes, dystonia and bradykinesia	No	Yes, dystonia	Severe, compatible with Parkinsonism; no tremor	Severe, compatible with Parkinsonism; in addition (rubral) tremor (3/s), increasing with action	Yes, (rubral) tremor (3/s), increasing with action; mild posturing
Eye movements	Saccadic pursuit	No fixation	Short periods of fixation	Normal	Normal	Saccadic pursuits and hypometric saccades	Saccadic pursuit	Saccadic pursuit and hypometric saccades	Saccadic pursuit
Highest motor achievement	Some head balance	Some head balance	Some head balance, tries to reach for objects	Walks with posterior walker, manages to walk 20 steps without support	Walking without support	Walking without support	Walking without support	Walking without support	Walking without support (age 14 mo), wheelchair dependent from age 12 yrs
Swallowing problems	Mild	Severe	Severe (nasogastric tube)	Yes, especially with liquids (prone to aspiration)	No	No	No	Severe dysphagia	Yes
Speech and language	None	None	None	Delayed (uses about 20 words, difficult to understand)	Mild delay in language development, at age 4 yrs., stutter	Speech delay, dysarthria	Severe dysarthria	Language deterioration from age 5 yrs., now anarthric	Severe dysarthria
Cognition	Severe global delay	Severe global delay assumed	Severe global delay	Not formally tested but seems normal	Mild learning difficulties	Not formally tested but seems normal	Learning disability	Learning disability	Normal
Epilepsy	Yes, myoclonic jerks from age 15 mo	No	No	No	No	No	No	No	No
Dentition	Abnormal (lack of maxillary incisors)	Abnormal (delayed dentition, deciduous molars first teeth to erupt)	Abnormal (lack of maxillary incisors)	Abnormal (delayed eruption of maxillary incisors)	Normal	Normal	Normal	Abnormal (first teeth to erupt maxillary incisors, 2 persisting decidual teeth)	Abnormal (molars first to erupt, incisors erupted at 4y of age)
Puberty development	n/a	n/a	n/a	n/a	n/a	n/a	Normal	Normal	Normal
Growth	Failure to thrive	Failure to thrive	Failure to thrive	Failure to thrive	Normal	n/a	Very low weight due to inadequate intake	Very low weight due to inadequate intake	Normal
Head circumference	Normal	Normal	Normal	Normal	Normal	Normal	Normal	Normal	Normal
Myopia	Not tested	Not tested	Not tested	No	Mild myopia	No	No	No	Mild myopia
Hearing loss	Not tested	Not tested	Abnormal BEAR	BEAR normal	Not tested, clinically normal	Not tested, clinically normal	Not tested, clinically normal	Not tested, clinically normal	Not tested, clinically normal
Other	n/a	Laboured breathing	Prone to respiratory tract infections; bacterial meningitis	n/a	n/a	n/a	n/a	n/a	n/a