Table e-2: Clinical features of 23 patients out of 17 families without mutations, arranged by decreasing age (at death) of the index patient

Patient (m/f)/ origin / Con-sang-uini-ty / Age (death) / Age at onset / Preg-nancy / Micro-cephaly (age: SD#) / Feeding difficulties (age tube fed) / Respira-tory failure (age) / Motor develop-ment / Speech develop-ment / Oph-thalmo-logic findings / Neurologi-cal findings / EMG/ muscle biopsy neuro-genic / ENG / CNS changes
11-1 (f)/ Austria / - / 7 yrs / 1 yr / Normal / n.a. / + (7 yrs) / n.a. / Sitting / None / n.a. / Hypotonia / +/+ / Normal / CH
12-1 (m)/ Pakistan7 / + / (4 yrs) / 4 mos / Normal / + (4 yrs) / + (4 yrs) / + / Head control / None / Normal / Hypotonia, spasticity and brisk reflexes in legs / +/+ / Normal / CH, megacisterna magna
13-1 (f)/ Africa / - / (2 5/12 yrs) / 3 mos / Normal / - (2 2/12 yrs: +0.5) / + (1.5 yrs) / + (12-15 mos) / None / None / Strabis-mus, reduced VEPs / Hypotonia, brisk reflexes / +/+ / Normal / CH
14-1 (f)/ Ger-many / - / 2 yrs / Birth / Normal / + (8 mos:-2) / - / - / Head control / None / Reduced vision / Hypotonia / +/n.a. / Normal / PCH
15-1 (f)/ Iran / + / (16 mos) / 4 mos / Normal / - (9 mos: -1.8) / + / - / Head control / None / Strabis-mus / Hypotonia / +/+ / Normal / CH, hypoplastic corpus callosum
16-1 (m)/ The Nether-lands / - / (10 mos) / Birth / Normal / - / + (4+7 mos) / + (4+7 mos) / None / None / Normal / Hypotonia, AMC / +/ (unspecific) / Normal motor NCV, absent SNAP / CH, delayed myelination, enlarged ventricles
17-1 (m)/ Turkey 7 / + / (3 mos) / Birth / Normal / - (birth: +1) / n.a. / + (birth) / None / None / Normal / Hypotonia / +/+ / Reduced motor NCV (6-9 m/s), absent SNAP / CH, enlarged ventricles
17-2 (m)/ Turkey7 / + / (2 wks) / Pre-natal / PH / - (birth: +1) / n.a. / + (birth) / None / None / Normal / Hypotonia, seizures from 2 dys / +/n.a. / Not measureable / CH
18-1 (f)/ Spain / - / (3 mos) / Pre-natal / PH / - / n.a. / + (birth) / None / None / n.a. / Hypotonia, axial spasticity / +/n.a. / Normal / CH, enlarged ventricles
19-1 (m)/ Spain / + / (3 mos) / Pre-natal / PH / - / + (birth) / + (birth) / None / None / n.a. / Hypotonia / +/+ / Reduced motor NCV, small and dispersed MAP (median nerve), absent SNAP / CH, mega cisterna magna
20-1 (m)/ Spain / - / (2.5 mos) / Pre-natal / PH / - / + / + / None / None / Pale papillae, reduced VEPs / Hypotonia, AMC / +/+ / Normal motor NCV, absent SNAP / CH, mega cisterna magna
21-1 (f)/ Ger-many / - / 2 mos / Pre-natal / PH / - (1 mo: + 0.5) / +(birth) / + (birth) / None / None / Normal / Hypotonia, AMC, newborn seizures / +/n.a. / Normal NCV, no MAP (tibial nerve), no SNAP (median nerve) / CH, mega cisterna magna, enlarged ventricles
22-1 (m)/ Norway / - / (2 mos) / Birth / Normal / + (3wks: -2) / + (birth) cleft lip / + (birth) / None / None / n.a. / Hypotonia,hyps-arrhythmia / n.a./+ / n.a. / PCH
23-1 (f)/ Pakistan8 / + / (1 mo) / Pre-natal / PH, IUGR / n.a. / + (birth) / + (birth) / None / None / Normal / Hypotonia, AMC / n.a./un-specific / Normal / CH, midbrain hypoplasia, enlarged ventricles
23-2 (f)/ Pakistan8 / + / (1.5 mos) / Pre-natal / PH, joint contractures / n.a. / + (birth) / +(birth) / None / None / Normal / Hypotonia, AMC, brisk reflexes / +/un-specific / n.a. / CH, midbrain hypoplasia, enlarged ventricles
24-1 (m)/ Ireland / + / (1 mo) / Pre-natal / Fetal akinesia, PH / n.a. / + (birth) / + (birth) / None / None / Normal / Hypotonia, seizures / Normal/
n.a. / n.a. / PCH, mega cisterna magna
25-1 (m)/ Italy / - / (18 dys) / Pre-natal / PH / n.a. / + (birth) / + (birth) / None / None / n.a. / Hypotonia / n.a./+ / n.a. / CH
25-2 (f)/ Italy / - / (2 dys) / n.a. / n.a. / n.a. / + (birth) / + (birth) / None / None / n.a. / Hypotonia / n.a./+ / n.a. / CH
26-1 (m)/ Canada / - / (2 dys) / Pre-natal / PH / n.a. / + (birth) / + (birth) / None / None / n.a. / Hypotonia, AMC / +/+ / n.a. / PCH
27-1 (m)/
The Nether-lands 3 / - / (1.5 hrs) / Birth / Normal / - (birth: 0) / + (birth) / + (birth) / None / None / n.a. / Hypotonia / n.a./n.a. / n.a. / n.a.
27-2 (f)/
The Nether-lands2 / - / (2 hrs) / Pre-natal / PH / n.a. / + (birth) / + (birth) / None / None / n.a. / Hypotonia / n.a./n.a. / n.a. / n.a.
27-3 (m)/
The Nether-lands2 / - / (1 dy) / Birth / Normal / n.a. / + (birth) / + (birth) / None / None / n.a. / Hypotonia, seizures from birth, AMC / n.a./n.a. / n.a. / PCH

CNS= central nervous system, CH=cerebellar hypoplasia, PCH=pontocerebellar hypoplasia, SD= standard deviation, AMC= arthrogryposis multiplex congenita, PH=polyhydramnios, IUGR= intrauterine growth retardation, EMG=electromyogram, ENG=electroneurogram, NCV= nerve conduction velocity, MAP = motor action potential, SNAP= sensory nerve action potential, VEPs= visual evoked potentials, yrs=years, mos=months, wks= weeks, dys= days, n.a.=not available,+=present, -=absent

# SD for head circumference according to WHO standards (

1