Table 1 Demographic and clinical characterization of individuals with the NF1 p.Met992del pathogenic variant

From: Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

NF1 feature

N (%)

≤8 years

9–18 years

≥19 years

All ages

Mutation-positive individuals [proband:relative]

45 [41:4]

50 [43:7]

40 [19:21]

135 [103:32]

Male:female

15:30

27:23

18:22

60:75

Fulfilling the NIH criteria if the family history is taken into account

31/43 (72.1)

43/49 (87.8)

23/39 (59)

97/131 (74.1)

Fulfilling the NIH criteria if solely taking the physical signs into account

20/43 (46.5)

36/49 (73.5)

20/39 (51.3)

76/131 (58)

>5 CALMs

41/45 (91.1)

48/50 (96)

30/40 (75)h

119/135 (88.2)

Skinfold freckling

20/39 (51.3)

35/48 (72.9)

18/37 (48.7)

73/124 (58.9)

Lisch nodules

3/34 (8.8)

6/43 (14)

4/24 (16.7)

13/101 (12.9)

Skeletal abnormalitiesa

5/39 (12.8)

9/48 (18.8)

7/38 (18.4)

21/125 (16.8)

Major external plexiform neurofibromas

0/44 (0)

0/46 (0)

0/38 (0)

0/128 (0)

Cutaneous neurofibromasb

0/43 (0)

0/47 (0)

0–1/38 (0–2.6)i

0–1/128 (0–0.8)

Subcutaneous neurofibromasb

0/42 (0)

0/46 (0)

0–3/36 (0–8.3)i

0–3/124 (0–2.4)

Symptomatic spinal neurofibromas

0/39 (0)

0/45 (0)

0/34 (0)

0/118 (0)

Symptomatic OPGsc

0/43 (0)

0/47 (0)

0/33 (0)

0/123 (0)

Asymptomatic OPGsd

0/11 (0)

1/19 (5.3)

0/11 (0)

1/41 (2.4)

Other neoplasmse

0/42 (0)

5/47 (10.6)

8/37 (21.6)

13/126 (10.3)

Cognitive impairment and/or learning disabilities

14/42 (33.3)

24/49 (49)

12/38 (31.6)

50/129 (38.8)

Noonan-like featuresf

3/42 (7.1)

6/43 (14)

6/34 (17.7)

15/119 (12.6)

Short statureg

2/24 (8.3)

6/32 (18.8)

3/15 (20)

11/71 (15.5)

Macrocephaly

12/32 (37.5)

8/40 (20)

6/15 (40)

26/87 (29.9)

Pulmonic stenosis

3/38 (7.9)

1/44 (2.3)j

0/31 (0)

4/113 (3.5)

  1. CALMs, café-au-lait macules; NF1, neurofibromatosis type 1; NIH, National Institutes of Health; OPG, optic pathway glioma.
  2. aAll bone abnormalities included, that is, scoliosis (n = 11), pectus abnormality (n = 9), mild winging of the scapula (n = 1), rib abnormality (n = 1), dysplastic vertebrae (n = 1), kyphosis (n = 1), and bilateral club feet (n = 1).
  3. bAt least two cutaneous/subcutaneous neurofibromas were required to be considered as “positive for the criterion of neurofibromas.”
  4. cThe absence of symptomatic OPGs was determined by ophthalmological examination and/or by magnetic resonance image (MRI).
  5. dIncluding only individuals without signs of symptomatic OPGs who underwent MRI examination.
  6. eAll “other” neoplasms, not including OPGs and neurofibromas, included, that is, astrocytomas (n = 3), oligodendroglioma (n = 1), lipomas (n = 5), angiolipoma (n = 1), hypothalamic glioma (n = 1), brain tumor with hamartomatous aspect by MRI of the encephalon (n = 1), neuroblastoma (n = 1), and craniopharyngioma (n = 1).
  7. fAn individual was classified as having Noonan-like phenotype when at least two of the following features were present: short stature, low-set ears, hypertelorism, downslanted palpebral fissures, midface hypoplasia, ptosis, webbed neck, and/or pulmonic stenosis.
  8. gAs no specific growth curves are available for the Hispanic and Asian populations, Hispanic and Asian individuals were excluded as having short or normal stature.
  9. hA possible explanation for a decreasing prevalence of CALMs in individuals ≥19 years is the fact that CALMs become fainter with age and some may even disappear entirely.
  10. iFour individuals with few (2–6) cutaneous or subcutaneous “neurofibromas”; none were biopsied and therefore none have been histologically confirmed.
  11. jThe presence of pulmonic stenosis was reported in the individual’s newborn period.
Back to article page