Table 1 Clinical features of individuals with SLC12A5 mutations.

Age, gender

4 years 8 months, female

3 years 1 month, female

1 year 11 months, male

20 years, female

Mutations

c.279 + 1G > C, p.Glu50_Gln93del; c.572C > T, p.Ala191Val

c.279 + 1G > C, p.Glu50_Gln93del; c.572C > T, p.Ala191Val

c.967T > C, p.Ser323Pro; c.1243A > G, p.Met415Val

c.953G > C, p.Trp318Ser; c.2242_2244del, p.Ser748del

Diagnosis

EIFMS

EIFMS

EIFMS

Intractable epilepsy (Possible EIFMS)

Initial symptom

Clonic seizure followed by tonic phase at day 1

Tonic seizure at day 3

Apneic episodes at 1.5 months

Upward eye deviation and cyanosis at day 1

Initial interictal EEG

Normal sleep background activity with slow waves over the left posterior area at 2 months

Normal sleep background activity at 2 months

Normal at 2 months

Unknown

Course of seizures

Focal tonic seizures at day 6; apnea, asymmetrical tonic posture with flushed face, twitching of fingers, left or right eyelid or mouth, eye deviation to the left or right at 1 month; seizure-free between 16 and 40 months; tonic seizures with vocalization, motion arrest with staring since 3 years 4 months

Upward eye deviation, tonic posture of arms followed by pedaling movements at day 3; apnea and clonic seizures of the left or right extremities at 1 month; seizure-free between 3 to 11 months; clonic seizures of one extremity evolving into other extremities, hyperventilation, tonic extension of the arms with apnea since 11 months

Apneic episode with loss of consciousness at 2 months; tonic seizures of extremities at 2.5 months; cyanotic starry-eyed episodes at 5 months; bilateral eye gazing and deviation of the head to either the right or the left, focal clonic movements involving different limbs at 6 months; brief, blank stare, deviation of eyes to one side, tonic posturing at 7 months

Clonic-tonic seizure at 2 days; upward eye deviation, tongue spasm, tonic posturing of unilateral extremities, tonic-clonic seizure at 6 months

Follow-up EEG

Runs of increment rhythmic θ activity over the bilateral frontocentroparietal areas during sleep at 13 months; occasional runs of HVS over the left frontal area and several spikes over the right frontal area during sleep at 3 years 6 months

Generalized high-voltage slow background of 2 Hz delta activity and no epileptiform activity during wakefulness at 1 year 9 months

Diffusely attenuated background with ventilation artifact at 6 months; normal EEG background with some spikes over the frontal region at 9 months; no electrographic seizures

Sharp waves over the left central and frontal region at 10 years; slow back ground activity of 5 Hz

Effective drugs

KBr, high-dose PB, AZM for apnea

KBr, high-dose PB, VPA

TPM, LEV, KD

Intractable (none)

Head control

1 year, but still unstable at 4 years 8 months

4 months to 5.5 months, regressed and lost head control from 5.5 months, regained some head control by 11 months.

1 year

Rolling over

2 years 6 months, but incomplete at 4 years 6 months

4 months to 5.5 months, regressed after 5.5 months, able to roll over again at 9–10 months

2 years

Sitting

Sits unsupported by 23 months, but still slightly unsteady

Meaningful words

Muscle tonus

Hypotonia

Hypotonia

Hypotonia

Hypotonia

Involuntary movements

Head circumference

34.0 cm (+0.3 SD) at birth; 43 cm (−4.7 SD) at 4 years 8 months

33.7 cm (+0.7 SD) at birth; 45.2 cm (−2.0 SD) at 3 years

35 cm (25^th centile) at birth; 46cm (3^rd centile) at 23 months

33 cm (−0.1 SD) at birth; 47.2 cm (−4.0 SD) at 10 years

Brain MRI

Thin corpus callosum, frontal and temporal lobes atrophy, delayed myelination at 2 months; same findings at 13 months

Thin corpus callosum, frontal lobe atrophy, delayed myelination, arachnoid cyst in the left posterior fossa at 5 months

Mild brain atrophy at 3 months

Subdural hygroma; bilateral hippocampal atrophy with high intensity on FLAIR image, mild atrophy of the cerebellum, delayed myelination of the temporal lobe at 10 years; progression of cerebellar atrophy at 20 years