Table 1.
Summary of genetic results and neurodevelopmental profiles for six novel patients
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | |
|---|---|---|---|---|---|---|
| Sex | M | F | M | M | M | M |
| Technology used to identify KMT2A variant | WGSa | WESb | WGSa | WGSa | WESb | Targeted sequencing |
| KMT2A variantc | p.(Ala3442Profs*17) | p.(Ser2363Leufs*12) | p.(Val2057Tyrfs*18) | p.(Glu2566Lysfs*14) | p.(Leu2848Pro) | p.(Arg2699*) |
| Inheritance | De novo | De novo | De novo | De novo | De novo | De novo |
| Other variants | None | Maternally inherited 295 kb deletion chr4q31.3d (chr4:151,378,576-151,673,967) | Maternally inherited PAX1 p.(G166A)d, e | None | Maternally inherited CHRNA4 c.(274-1 G > A)d, f | None |
| Age at Neurodevelopmental Assessment | 10 y 3 m | 12 y 2 m | 13 y 1 m | 25 y 3 m | 5 y1m | 5y 9 m |
| Intellectual Disability Diagnosis | + | + | + | − | + | + |
| IQ (percentile) | <1st | 3rd | <1st | 4th | <1st | <1st |
| Overall Adaptive Skills (percentile) | 4th | 1st | <1st | 9th | <1st | <1st |
| Language Skills (OWLS-IIg percentile) | <1st | <1st | <1st | 32nd | <1st | 1st |
| Receptive Vocabulary (PPVT-4h percentile) | 16th | 9th | 1st | 70thi | <1st | 7th |
| Expressive Vocabulary (EVT-2j percentile) | 7th | 5th | <1st | N/Ak | <1st | 1st |
| ASD Diagnosis | + | − | + | + | + | + |
| Rigidity/ Poor flexibility | + | + | + | + | + | + |
| Anxiety Symptoms | − | +l | + | − | − | + |
| Attention Concerns | +m | +m | + | − | + | + |
| Emotional Regulation Concerns (Dysregulation) | + | + | + | −n | + | + |
| Externalizing Behaviours | + | − | + | − | + | + |
aWhole-genome sequencing
bWhole-exome sequencing
cKMT2A transcript used is NM_0011904.1
dVariant of unknown significance, not clinically significant
ePAX1 transcript used is NM_006192
fCHRNA4 transcript used is NM_000744.6
gOral and Written Language Scales, Second Edition
hPeabody Picture and Vocabulary Test, Fourth Edition
iBased on previous assessment at 19 y
jExpressive Vocabulary Test, Second Edition
kEVT-2 not administered. Expressive language skills from OWLS-II
lHas diagnosis of Generalized Anxiety Disorder
mHas diagnosis of Attention Deficit Hyperactivity Disorder
nBehavior Rating Inventory of Executive Function not administered due to age. Information based on Antisocial Personality Problem Scale on the Adult Behavior Checklist as well as parent report