Table 1 Genetics, clinical, and MRI findings of cases in this study

1

8 m

F

EXOSC3

NM_016042.4

c.395A > C

p.D132A

Missense (Homozygous)

P

PM3, PP1, PS3, PM2, PP3

0.07%

0.03%

Deleterious

Cerebral atrophy, cerebellar atrophy

Hypotonia, hyperreflexia, spasticity, No hearing or visual impairment, neurodevelopmental delay, seizure (died at three years old)

Pontocerebellar hypoplasia, type 1B

2

2 y

M

EXOSC3

NM_016042.4

c.395A > C

p.D132A

Missense (Homozygous)

P

PM3, PP1, PS3, PM2, PP3

0.07%

0.03%

Deleterious

Cerebellar atrophy

Severe developmental delay, psychomotor regression, mental retardation, Poor head control, speech delay, hypotonia in legs, muscle weakness, spasticity

Pontocerebellar hypoplasia, type 1B

3

10 m

F

TSEN2

NM_001145394.2

c.749A > G

p.D250G

Missense (Homozygous)

VUS

PM2, BP4

0.0004%

N.A

Benign

N.A

Severe FTT, severe developmental delay, developmental regression (normal up to 4 month), microcephaly, refractory seizure and hypotonia (died at age of 6 years old)

Pontocerebellar hypoplasia type 2B

4

3 y

M

SEPSECS

NM_006493.4

c.208T > C

p.C70R

Missense (Homozygous)

VUS

PM2, PP3

N.A

N.A

Deleterious

N.A

Truncal hypotonia, mental retardation, developmental delay, delay in walking, speech delay, febrile seizure and strabismus

Pontocerebellar hypoplasia type 2D

5

4 y

M

SEPSECS

NM_016955.4

c.1274A > G

p.H425R

Missense (Homozygous)

VUS

PM2, PP3

0.0003%

N.A

Deleterious

Cystic cerebellar degeneration

Developmental and motor delay, mental retardation, febrile seizure, spasticity, nystagmus, ataxia and neuropathy (pain sensation)

Pontocerebellar hypoplasia type 2D

6

3.5 y

M

TSEN54

NM_207346.3

c.1160G > T

p.R387L

Missense (Homozygous)

VUS

PM2

0%

N.A

Deleterious

Atrophy of cerebellum vermis

Meconium aspiration, developmental delay, motor delay, muscle weakness, speech delay, ataxia

Pontocerebellar hypoplasia type 2A/4/5

7

2.5 y

M

TOE1

NM_025077.4

c.1476C > G

p.F492L

Missense (Homozygous)

VUS

PM2

N.A

N.A

Deleterious

Delayed in white matter myelination

Developmental delay, ambiguous genitalia, strabismus, spasticity, hyperreflexia, microcephaly

Pontocerebellar hypoplasia, type 7

8

1 y

M

AMPD2

NM_001368809.2

c.1858C > A

p.R620S

Missense (Homozygous)

P

PM2, PM3, PM5, PP2, PP3

N.A

N.A

Deleterious

Periventricular white matter abnormality, elevated lactate level in MRS

Progressive microcephaly, Absent development, seizure, axial hypotonia, spasticity, poor fixation of eye

Pontocerebellar hypoplasia, type 9

9

4 y

F

CLP1

NM_006831.3

c.784C > G

p.L262V

Missense (Homozygous)

VUS

PM2

0.0005%

N.A

Deleterious

No Abnormal findings in MRI

Motor delay (lack of independent walking), lack of speech, hypotonia, hyperreflexia, epileptic vertigo or dizziness (EVD)

Pontocerebellar hypoplasia, type 10

10

4.5 y

F

CLP1

NM_006831.3

c.419G > A

p.R140H

Missense (Homozygous)

P

PP1,  PP3, PS3,   PM2

0.0018%

0.0008%

Deleterious

Cortical atrophy, enlarged ventricular

Poor growth, progressive microcephaly, hypotonia, tonic seizure and developmental and motor delay (lack of independent sitting or walking), lack of speech, scoliosis, sensory neuropathy, strabismus

Pontocerebellar hypoplasia, type 10

11

8 m

M

CLP1

NM_006831.3

c.419G > A

p.R140H

Missense (Homozygous)

P

PP1,  PP3, PS3,   PM2

0.0018%

0.0008%

Deleterious

cerebral and cerebellar atrophy, Leukodystrophy

Seizure, developmental delay, progressive microcephaly, hypertonia, spasticity (died at age of 20 months)

Pontocerebellar hypoplasia, type 10

12

13 m

M

TBC1D23

NM_001199198.3

c.458T > C

p.M153T

Missense (Homozygous)

VUS

PM2

0.0004%

0.0017%

Deleterious

generalized brain atrophy

Delayed psychomotor development, Intellectual disability, language delay, inability to walk, hypotonia (early infancy), muscle atrophy, generalized spasticity, dysphagia, recurrent respiratory infections, happy demeanor, autistic features

Pontocerebellar hypoplasia, type 11