Table 1 overview of clinical, genetic and brain MRI’s data of TAOK1-related NDDs reported patients (including our clinical report). Extensive information are in Supplementary Materials. Abbreviations SD = Standard Deviations; ADHD = Attention Deficit Hyperactivity Disorder; ASD = Autism Spectrum Disorder; PVNH = Periventricular Nodular Heterotopia; CC = corpus callosum. Notes (a) = patient N #23 reported by Van Woerden et al. 2021 is originally described by Xie et al. 2016 (Xie et al., 2016); (b) = Macrocephaly is defined as OFC ≥ 2 SD; (c) = “global developmental delay” refers to a delay in two or more developmental domains (gross motor/fine motor, cognitive, speech/language, personal/social, activities of daily living) in children younger than 5 years of age; (d) = “autism and autistic features” refers either to children with established diagnosis of ASD and children with mild autistic traits that do not satisfy the diagnostic criteria for ASD by standard scales

Gender

males: 14/23

males: 5/8

males 2/4

male

female

male

males: 23/38 (58%)

Type of mutation

frameshift 5/23

splicing 3/23

missense 5/23

nonsense 6/23

exon deletion 1/23

large deletion 3/23

frameshift 1/8

missense 4/8

nonsense 3/8

frameshift 2/4

splicing 1/4

missense 1/4

frameshift

splicing

nonsense

frameshift 9/38

splicing 5/38

missense 10/38

nonsense 10/38

large deletion 3/38

exon deletion 1/38

Inheritance

de novo 16/19

inherited 3/19

de novo 8/8

de novo 2/4

inherited 2/4

De novo

De novo

N/A

de novo: 28/33 (84%)

inherited: 5/33

Brain MRI

normal 11/17

unspecific findings 6/17 (arachnoid cyst, incomplete hippocampal inversion, hydrocephalus, thinning of CC, ventriculomegaly, Chiari I malformation, delayed myelination).

1/1 “leukodystrophy”

4/4 unspecific findings (arachnoid cyst, ventriculomegaly, mild bilateral parietal volume loss, multifocal subcortical gliosis consistent with perinatal injury)

N/A

N/A

PVNH, arachnoid cyst, thinning of CC

11/23: normal (48%)

11/23 unspecific findings

1/23: PVNH (+ unspecific findings)

Dysmorphic facial features

9/9 (mostly high forehead, downslanting palpebral fissures, bulbous nose, micrognathia)

6/8 (mostly large or high forehead, downslanting palpebral fissures, low set ears).

3/4 (mostly prominent forehead)

N/A

frontal bossing

high forehead, long and pronounced philtrum, bulbous nose, uplifted earlobes

20/23 (87%)

Macrocephaly^(b)

8/20

3/8

3/4

Yes

Yes

Yes

16/35 (46%)

Global developmental delay^(c)

18/20

6/8

4/4

N/A

No

Yes

29/34 (85%)

Intellectual disability

15/21

4/8

2/2

No

No

No

21/34(69%)

ADHD or attention issues

4/20

2/8

1/3

N/A

No

No

7/33 (21%)

ASD or autistic features^(d)

5/17

2/8

2/3

Yes

No

Yes

11/31 (35%)

Hypotonia

12/21

6/8

4/4

N/A

No

No

22/35 (63%)

Joint hypermobility

7/21

2/8

3/3

N/A

N/A

No

12/33 (36%)

Seizures

2/2

1/8

1/4 (complex febrile seizures)

N/A

N/A

No

4/15 (27%)

Eyes/visual problems

7/19 strabismus, refraction’s abnormality, cataracts

1/8

2/4 (strabismus, ptosis, refraction’s abnormality)

N/A

N/A

acquired left-eye esophoria

11/32 (34%)

History of feeding difficulties

11/20 (swallowing difficulties, reflux, drooling)

1/1 (swallowing and oral motor difficulties)

3/4

N/A

N/A

No

15/26 (58%)