Table 2.
Comparison of Clinical Features of the Arg1809 Cohort with the NF1 p.Met992del Cohort (Upadhyaya et al., 2007) and Previously Reported Large‐Scale NF1 Patient Cohorts
| Number of patients (%) | P value (2‐tailed Fisher's exact test) | ||||||
|---|---|---|---|---|---|---|---|
| NF1 feature | p.Arg1809a | p.Met992delb | Legiusc | Previous NF cohortsd | p.Arg1809 versus p.Met992del | p.Arg1809 versus Legius syndrome | p.Arg1809 versus previous NF cohorts |
| >5 CALMs (and size appropriate for age) | 124/136 (91.2) | 46/47 (97.9) | 110/142 (77.5) | 1210/1297 (93.3)B,C,E | 0.0018 ↗ | ||
| Skinfold freckling (SF)e | 54/80 (67.5) | 30/47 (63.8) | 42/89 (47.2) | 661/960 (68.9) B,C,E | 0.0086 ↗ | ||
| >5 CALMs and SF, age ≥9 year | 52/80 (65) | 22/34 (64.7) | 35/92 (38) | estimated at 95% (95) | 0.0005 ↗ | <0.0001 ↘ | |
| Lisch nodules | 10/91 (11.0); 10/119 (8.4) | 3/30 (10) | 0 (n unknown) | 82/88 (93.2) A | <0.0001 (<0.0001) ↘ | ||
| Cutaneous neurofibromasf | 5g/39 (12.8); 5g/59 (8.5) | 0/18 (0) | 0/68 (0) | 99/99 (100) A | <0.0001 (<0.0001) ↘ | ||
| Major external plexiform neurofibromase | 0/78 (0); 0/107 (0) | 0/41 (0) | 0/95 (0) | 7/115 (6.1) A | 0.0429 (0.0146) ↘ | ||
| Symptomatic optic pathway glioma, age ≥5 yr | 0/98 (0)h; 0/119 (0)i | 0/46 (0) | 0/118 (0) | 66/1383 (4.8)A,E, G,H,I | 0.0193 (0.0081) ↘ | ||
| Noonan syndrome featuresj | 32/122 (26.2) | 4 (all from 1 family) | 19 reported | 12/94 (12.8) | |||
| Pulmonic stenosis | 13/105 (12.4) | 4/47 (8.5) | 3 reported | 25/2322 (1.1) F | <0.0001 ↗ | ||
| Short staturek | 29/82 (35.4) | 5/47 (10.6) | 10/85 (11.8) | 109/684 (15.9) A,B | 0.0019 ↗ | 0.0004 ↗ | <0.0001 ↗ |
| Macrocephaly | 20/80 (25) | 4/45 (8.9) | 25/111 (22.5) | 239/704 (33.9) A,B | 0.0335 ↗ | ||
| Scoliosisl | 6/71 (8.5) | 2/20 (10) | 5 reported | 11/96 (11.5) A | 0.0467 ↘ | ||
| Pectus abnormalities | 9/125 (7.2) | 7/45 (15.6) | 15 reported | 36/127 (28.3) D | <0.0001 ↘ | ||
| Cognitive impairment/ learning disorders | 71/127m | 8/47 (17) | 15/53 (learning disabilities); 12/56 (psychomotor developmental delays); 11/52 (A(D)HD, autistic behaviour)n | 190/424 (44.8) A,E | |||
First value are data from this study; second values are the data combined from this and previous studies (Ekvall et al., 2014; Nyström et al., 2009; Pinna et al., 2015; Santoro et al., 2015); between round brackets: percentages.
Upadhyaya et al. (2007).
Data compiled from Brems et al. (2007) (excluding UAB31,43,48,88, as these are included in Messiaen et al. (2009)) (Denayer et al., 2011; Messiaen et al., 2009; Pasmant et al., 2009; Spurlock et al., 2009). For some features, total number of cases assessed for a given feature is unknown; only the number of observations is known and is stated here as summarized by Brems et al. (2012).
Previous NF1 cohorts used for comparison: A: Huson et al. (1988); B: Khosrotehrani et al. (2005); C: Huson et al. (1989aa, Huson et al., 1989b); D: Cnossen et al. (1998); E: McGaughran et al. (1999); F: Lin et al. (2000); G: Listernick et al. (1994); H: Singhal et al. (2002); I: Blazo et al. (2004).
In patients ≥9 years in this study and ≥10 years in other studies.
In patients ≥19 years in this study and ≥20 years in other studies.
Five individuals with few (1–6) small, subdermal “possible neurofibromas,” none were biopsied and therefore none have been histologically confirmed, therefore this is a very conservative estimate.
Including 31 aged ≥5 years who had an MRI and no asymptomatic OG present.
Including 34 aged ≥5 years who had an MRI and no asymptomatic OG present.
A patient was classified as having “Noonan‐syndrome features” when at least 2 of the following features were present: short stature, low set ears, hypertelorism, midface hypoplasia, webbed neck, or pulmonic stenosis.
Short stature defined as ≤PC3 in the Arg1809 and Met992del cohort, in Huson et al. (1988), but as <PC5 in the Legius cohort.
In patients ≥9 years in this and previous studies.
Three individuals with said normal development and ADD (2) and ADHD (1) were counted as normal but included toward the total number of cases in the denominator.
Data as summarized in Brems et al. (2007).