Table 1.
Comparison of frequency of observed features between NF1 p.Met992del patients in this cohort, the Koczkowska et al cohort [20], and molecularly unsegregated NF1 cohorts detailed in the literature [3, 21–25].
| NF1 feature | Frequency | Comparison of current cohort to Koczkowska et al. [20] (P value from 2-tailed Fisher’s exact test) | Comparison of those with p.Met992deli with classic phenotype (P value from 2-tailed Fisher’s exact test) | |||||
|---|---|---|---|---|---|---|---|---|
| Current cohort | Koczkowska et al. [20] [n = 135] (%) | Molecularly unsegregated NF1 patient cohort (%) [3, 21–25] | ||||||
| <7 years [n = 7] (%) | ≥7–18 years [n = 16] (%) | ≥19 years [n = 17] (%) | All* [n = 41] (%) | |||||
| ≥6 Café-au-lait (CAL) macules (HP:0000957) | 6/7 (85.7) | 14/16 (87.5) | 17/17 (100) | 38/41 (92.7) | 119/135 (88.2) | 4058/4419 (91.8) [21, 24] | →P = 0.57 | →P = 0.21 |
| Intertriginous frecklinga (HP:0000997 and HP:0030052) | 2/7 (28.6) | 10/16 (62.5) | 13/17 (76.5) | 26/41 (63.4) | 73/124 (58.9) | 3335/4242 (78.6) [21, 24] | →P = 0.71 | ↓P < 0.0001 |
| Lisch nodules (HP:0009737) | 0/7 (0) | 0/11 (0) | 2/6 (33.3)b | 2/25 (8.0) | 13/101 (12.9) | 2637/3983 (66.2) [21, 24] | →P = 0.73 | ↓P < 0.0001 |
| Cutaneous neurofibroma | 0/6 (0) | 0/16 (0)c | 0/17 (0) | 0/40 (0) | 0-1/128 (0-0.8) | 336/506 (66.4) [21, 25] | →P = 1.00 | ↓P < 0.0001 |
| Subcutaneous dermal neurofibroma (HP:0100698) | 0/7 (0) | 0/16 (0) | 1/17 (5.9) | 1/41 (2.4) | 0-3/124 (0-2.4) | 260/471 (55.2) [21, 25] | →P = 1.00 | ↓P < 0.0001 |
| Plexiform neurofibroma (HP:0009732) | 0/7 (0) | 0/16 (0) | 0/17 (0) | 0/41 (0) | 0/128 (0) | 1182/4419 (26.7) [21, 24] | →P = 1.00 | ↓P < 0.0001 |
| Spinal neurofibromasd (HP:0009735) | 0/0 (0) | 0/4 (0) | 0/2 (0) | 0/6 (0) | 0/118 (0) | 33/139 (23.7) [21] | →P = 1.00 | ↓P < 0.0001 |
| Optic gliomad (HP:0009734) | 0/4 (0) | 0/8 (0) | 0/2 (0) | 0/15 (0) | 1/164 (0.6) | 16/141 (11.3) [21] | →P = 1.00 | ↓P < 0.0001 |
| Other neoplasm (HP:0002664) | 0/7 (0) | 0/16 (0) | 1/17 (5.9)e | 1/41 (2.4) | 13/126 (10.3) | 397/3643 (19.9) [22] | →P = 0.19 | →P = 0.37 |
| Scoliosis (HP:0002650) | 0/7 (0) | 4/16 (25.0) | 2/17 (11.8) | 6/41(14.6) | 11/125 (8.8) | 101/663 (15.2) [21, 25] | →P = 0.37 | →P = 0.11 |
| Short staturef (HP:0004322) | 1/6 (16.7) | 1/12 (8.3) | 2/9 (22.2) | 4/27 (14.8) | 11/71 (15.5) | 29/124 (23.4) [3] | →P = 1.00 | →P = 0.17 |
| Macrocephalyg (HP:0000256) | 1/6 (16.7) | 1/7 (14.3) | 1/11 (9.1) | 3/24 (12.5) | 26/87 (29.9) | 39/115 (33.9) [3] | →P = 0.12 | →P = 0.25 |
| Pulmonary stenosis (HP:0001642) | 0/6 (0) | 0/13 (0) | 0/16 (0) | 0/36 (0) | 4/113 (3.5) | 25/2322 (1.1) [23] | →P = 0.57 | →P = 0.09 |
| Learning difficulty/cognitive impairmenth (HP:0100543) | 4/6 (66.7) | 10/16 (62.5) | 5/17 (29.4) | 19/40 (47.5) | 50/129 (38.8) | 43/138 (31.2) [21] | →P = 0.36 | →P = 0.10 |
*One age unknown at review
aMust be more than one freckle observed to be included.
bOne patient unilateral, one patient bilateral, total n number of patients represents those in which a dedicated eye examination was done.
cNeurofibromas had to be histologically confirmed to be included. One patient aged 11 reported to have multiple cutaneous lesions but no histology available.
dFrequency only measured from cases who had undergone MRI imaging.
eBladder cancer identified in 70-year-old female.
fShort stature defined as height/length <3rd centile, no specific growth charts are available for Asian / Hispanic populations and therefore these individuals were excluded.
gMacrocephaly defined as head circumference >98th centile.
hOne comparator group used for learning difficulty (older classical cohorts not utilised as definitions of learning difficulty have changed over time). One patient excluded as <1 year of age and therefore level of learning difficult to assess.
iKoczkowska et al. cohort combined with present cohort.
↑NF1 c.2970_2972del cohort has a statistically significant higher frequency of this feature.
→NF1 c.2970_2972del cohort has an equivalent frequency.
↓NF1 c.2970_2972del cohort has a statistically significant lower frequency of this feature.