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Bone et al. J Transl Genet Genom 2022;6:169-78 https://dx.doi.org/10.20517/jtgg.2021.56 Page 173

Table 1. Demographics and Clinical Features
Gender (M:F) 11:5
Genotype: Deletions – 5 (3 large deletions involving multiple genes)
Missense – 6
Nonsense – 3
Duplication – 1
Age Range at first EEG 15 months to 9 years
(mean, SD) (3.75 years, SD 2.25 years)
Clinical Features Developmental Delay – 16
Epilepsy – 5
Breath-Holding Spells – 7
EEG Abnormalities Epileptiform Discharges – 4
Focal Slowing – 5
Generalized Slowing – 5
MRI Abnormalities Normal : Abnormal – 4:9
Hypoplasia or Atrophy – 6
Corpus Callosal Dysplasia – 4
Gliosis – 2
Myelination Abnormalities – 2
Microcephaly – 1
This table summarizes the patient demographics, clinical features, genotype, EEG findings, and MRI Brain findings. SD: standard deviation. EEG:
electroencephalogram.

abnormal brain MRIs among patients with an abnormal EEG compared to patients with only normal EEGs
(8/9 vs. 3/7, P = 0.03). When assessed individually, there was not a significant difference in the rates of
abnormal MRI brain among patients with epileptiform discharges, generalized slowing, or focal slowing. To
assess the relationship between developmental motor abilities and abnormal EEGs, we dichotomized delays
in ambulation to at least 1-year delayed or at least 3-year delayed onset of ambulation. There was no
significant relationship between abnormal EEGs and delayed ambulation of 1-year or greater, but there was
a higher prevalence of abnormal EEGs among those patients with a 3-year or greater delay in ambulation (P
= 0.2 vs. 0.03, respectively).

We also assessed genotype-phenotype correlations. Our cohort included a range of genotypes: large
deletions (5/16), missense variants (6/16), nonsense variants (3/16), and one duplication. Because of prior
studies demonstrating a higher prevalence of epilepsy in patients with missense variants, we evaluated the
relationship between clinical severity in those with missense variants in comparison to non-missense
variants. Rates of abnormal EEGs, abnormal brain MRIs, diagnosis of epilepsy, and delayed ambulation
were similar between both groups. Delayed ambulation was a ubiquitous finding among all 16 individuals.
Epilepsy was present in 2/5 with a large deletion, 2/7 with a missense variant, and 1/3 with a nonsense
variant. Abnormal EEGs were present in 3/5 with a large deletion, 4/7 with a missense variant, and all 3 with
a nonsense variant. The one patient with a duplication did not have epilepsy, and his EEG was normal .
[1]

DISCUSSION
This review of EEGs in patients with PTHS showed that there was no characteristic pattern, and
approximately half of the patients had normal EEGs. In patients with abnormal EEGs, focal epileptiform
abnormalities were more common than generalized, and none of the patients had only generalized spikes.
In contrast to a recently published series of 21 patients with PTHS in which 4.8% of their cohort (1/21
patients) had no epileptiform discharges on prolonged EEG (3), we found a much higher proportion of
normal EEGs (7/16, 43%). However, both studies support the finding that there is no characteristic
signature EEG pattern in PTHS and focal epileptiform discharges with focal-onset seizures appear to be
more common than generalized discharges and seizures . This variance could be explained by varying
[3]