Recessive mutations in ATP8A2 cause severe hypotonia, cognitive impairment, hyperkinetic movement disorders and progressive optic atrophy

Table 1 Clinical characteristics of individuals with ATP8A2 mutations

Patients	1	2	3	4	5	6	7	8	9	10	11	Total^a
Gender	F	F	F	F	M	F	M	M	F	F	F
Symptom onset	Birth	Birth	Birth	Birth	6 mos	4 mos	Birth	6 mos	Birth	Birth	1 mos
Current age (years)	5y	2.5y	2.7y	6y	5y	9y	15y	16y^b	28y	8.5y	5.5y
Gestational age (wk)	40	39	41	40	39	39	40	40	Term	40	39
Birth weight (kg)	4.14	3.57	3.09	4.55	2.62	2.70	2.90	N/a	N/a	3.19	2.87
Clinical features
Hypotonia onset	Birth	Birth	Birth	Birth	Infancy	Infancy	Birth	Infancy	Birth	Birth	Infancy
Hypotonia persists?	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	100%
Muscle weakness	Yes	Yes	Yes	N/a	No	Yes	Yes	N/a	N/a	Yes	Yes	80%; 8/10
Optic Atrophy	Yes	N/a	Yes	Yes	Yes	No	No	Yes	N/a	Yes	Yes	78%; 7/9
Ophthalmoplegia	No	No	No	Yes	No	No	No	Yes	Yes	Yes	Yes	45%
Ptosis	No	No	Yes	Yes	No	No	No	No	Yes	No	Yes	36%
Hearing Loss	No	No	No	Yes	Yes	No	No	No	No	No	No	18%
Seizures	No	No	No	No	No	No	No	Yes	Yes	No	No	18%
Feeding difficulties	Yes, G-tube	Yes, G-tube	Yes	No	Yes	Yes	Yes	Yes	Yes, G-tube	Yes	Yes	91%
Sleep disturbance	Yes	Yes	No	N/a	No	Yes	No	No	No	No	Yes	40%; 4/10
Movement disorder
Chorea or choreoathetosis	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	100%
Dystonia	Yes	No	Yes	Yes	No	No	No	No	No	No	Yes	36%
Facial dyskinesia	No	No	No	No	No	No	No	No	No	Yes	Yes	18%
Current head size (OFC)	25%ile	25%ile	5%ile	< 2%ile	10%ile	2%ile	15%ile	< 3%ile	< 2%ile	25%ile	< 2%ile
Current weight	25%ile	83%ile	60%ile	N/A	< 3%ile	< 2%ile	< 2%ile	< 3%ile	< 2%ile	< 3%ile	< 3%ile
Current length/height	85%ile	90%ile	40%ile	N/A	25%ile	< 2%ile	< 2%ile	< 3%ile	< 2%ile	5%ile	20%ile

^aDenominator = 11 unless otherwise indicated; F female, M male, y years old, mos months old, wk weeks, N/a not available, %ile percentile, OFC occipitofrontal head circumference, NCS/EMG nerve conduction study and electromyography, BAER brainstem auditory evoked response, ^bDeceased

ISSN: 1750-1172