Table 3.

Studies that have investigated children with isolated CALM but no other NF1-associated disease features and without an affected first-degree relative by means of comprehensive genetic testing of the NF1 gene (and the SPRED1 gene)

Total number of patients investigated	Age of the patients	Number of CALM	Number of patients with pathogenic variants in the NF1 gene	Number of patients with pathogenic variants in the SPRED1 gene	Number of patients without a pathogenic variant	References
44	≤ 9 Years	≥ 6	28 (63.6%)	1 (2.3%)	15 (34.1%)	Giugliano et al. (2019)
71	0–7 Years (N = 42);  > 7 Years (N = 8); age unknown (N = 21)	≥ 6	34 (47.9%)a	3 (4.2%)b	25 (35.2%)	Castellanos et al. (2020)
95	≤ 14 Months	≥ 6	84 (88.4%)	Not investigated	11 (11.6%)	Ben-Shachar et al. (2017)c
65	> 14 Months and ≤ 29 months	≥ 6	45 (69.2%)	Not investigated	20 (30.8%)	Ben-Shachar et al. (2017)c
38	≤ 14 Months	< 6	6 (15.8%)	Not investigated	32 (84.2%)	Ben-Shachar et al. (2017)c

^aIn addition to 34 pathogenic NF1 variants, 7 patients with missense NF1 variants of unknown significance (VUS) were identified. Thus, the total number of NF1 variants identified was N = 41 (57.8%)

^bIn addition to 3 pathogenic SPRED1 variants, two patients with SPRED1 variants of unknown significance (VUS) were identified. Thus, the total number of SPRED1 variants identified was N = 5 (7%)

^cIn this study, patients under suspicion of segmental NF1 were excluded but children were not tested for possible generalized mosaic NF1