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
| Paper | van Woerden 2021(a) | Dulovic-Mahlow 2019 | Hunter 2022 | Wang 2023 | Basel-Salmon 2021 | OUR PATIENT | TOTAL |
|---|---|---|---|---|---|---|---|
| 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%) |