BACKGROUND: Piebaldism is a rare, autosomal dominant, and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SLUG genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder.
METHODS: In this paper, we report a case of piebaldism with café-au-lait macules resulting from a novel mutation of KIT gene c.1982C > T (p.Thr661Ile) in a three-generation Chinese family. The whole-exome sequencing, mitochondrial gene 3000X, and bioinformatics tools were used to identify the mutation in this new-found pedigree. In addition, we searched the databases of \"Punmed, Chinese National Knowledge Infrastructure, CMJD, WANFANG MED ONLINE\", reviewed 88 cases of piebaldism caused by KIT gene mutation, and summarized the relationship between clinical phenotype and genotype of piebaldism through logistic regression and other statistical methods.
RESULTS: The proband and her affected mother carried a heterozygous c.1982C > T missense mutation (p.Thr661Ile) on KIT gene. Bioinformatics analysis hinted that it had potential pathogenicity. The data showed that piebaldism patients with cafè-au-lait macules had KIT mutations almost located in the intracellular tyrosine kinase domain and were mostly related to the severe clinical phenotype of piebaldism.
CONCLUSIONS: The new heterozygous c.1982C > T missense mutation on KIT caused piebaldism with café-au-lait macules in this Chinese family. This study provides a new reference index for clinicians to judge the severity of clinical phenotypes of piebaldism, broadens the understanding of the correlation between clinical phenotypes and genotypes of piebaldism, and provides reference of genetic counseling and prenatal diagnosis for affected families.

BACKGROUND: Conventional high fluence Q-switched (HFQS) Alexandrite 755-nm are widely used in clinical café-au-lait macules (CALMs) treatment. There have been recent concerns regarding the efficacy and safety of low fluence Q-switched (LFQS) Nd: YAG 1064-nm lasers.
OBJECTIVE: To evaluate the efficacy and safety of the conventional HFQS and LFQS laser in the treatment of CALMs.
METHODS: Within 3 months, 20 patients underwent prospective self-controlled split-lesion treatments with HFQS once or twice depending on the recovery rate, and with LFQS six times biweekly. Then the more effective laser was selected for continued treatments. Efficacy outcomes were evaluated by a visual analog scale (VAS) biweekly during the comparative trail. Recovery process, side effects and recurrence were recorded during the trial and follow-up visit. Patient and physician preferences for laser selection were also recorded.
RESULTS: The average VAS scores of areas treated with HFQS and LFQS were 2.92 ± 0.86 and 2.93 ± 1.13, respectively (p > 0.05). The most significant efficacy change of LFQS was after the fourth laser treatment (VAS score: 1.82-2.37, p < 0.001). 11 lesions treated with LFQS and 7 with HFQS achieved an optimal treatment response (3.67 ≤ VAS ≤ 4). Three patients relapsed on one side (one on LFQS, two on HFQS) and five on both sides. Adverse effects included temporary hypopigmentation, hyperpigmentation, uneven pigmentation, and mottled hypopigmentation. Doctors thought 80% of patients were suitable for LFQS. 70% of patients preferred LFQS posttreatment.
CONCLUSIONS: The efficacy difference between the LFQS 1064-nm laser and HFQS 755-nm laser in treating CALMs in a 3-month comparative trial was statistically insignificant. LFQS is preferred by doctors and patients and is likely to help more patients achieve treatment efficacy than the HFQS within a short time, with fewer temporary adverse reactions, and a more even pigmentation. But it can cause mottled hypopigmentation. The LFQS had obvious lesion clearance after the fourth treatment.

Many types of lasers have been used to treat café-au-lait macules (CALMs) since the introduction of the selective photothermolysis theory. However, the efficacy and safety of picosecond lasers, compared with those of nanosecond lasers, have not been researched. To compare the efficacy and safety of 755 nm picosecond laser (PS-755 nm), Q-switched (QS) Alexandrite 755 nm nanosecond laser (QS-755 nm), and QS Nd:YAG 532 nm nanosecond laser (QS-532 nm) for treating CALMs.
Forty-one patients received several treatments at 3-month intervals. Lesions were divided into two or three approximately equal parts, which were randomly treated with PS-755 nm, QS-755 nm, and QS-532 nm. The safety and efficacy of three lasers were determined based on blinded visual assessments and self-reports of patients three months after the comparative trial.
Visual assessment 3 months after the comparative trial revealed that there was no statistically significant difference among the sites treated by QS-755 nm (2.84 ± 1.11), QS-532 nm (2.63 ± 1.06), and PS-755 nm (2.74 ± 1.05) lasers. Five (26.32%) of 19 patients showed lesion recurrence. Adverse effects included acneiform miliaris, hypopigmentation, and hyperpigmentation, which were resolved within 12 months. Five (26.32%) of 19 patients who showed lesion recurrence 1-5 months after laser treatment had lightened or cleared at least 50% of the lesion. 46.67% of patients were satisfied or very satisfied with the outcome of the overall treatment.
PS-755 nm, QS-755 nm, and QS-532 nm laser treatments were equally effective in treating and improving CALMs. PS-755 nm caused fewer adverse effects. Individuals can react differently to different types of lasers. Patch tests should be conducted before the treatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Neurofibromatosis 1 (NF1) is one of the most common dominantly inherited genetic disorders worldwide, with an age-dependent phenotypic expression. Exploring the mutational spectrum and clinical presentation of NF1 patients at different ages from a diverse population will aid the understanding of genotype-phenotype correlations.
In this study, 95 Chinese children with clinical suspicion of NF1 mainly due to the presence of multiple café-au-lait macules (CALMs) were subjected to medical exome-sequencing analysis and Sanger confirmation of pathogenic variants. Clinical presentations were evaluated regarding dermatological, ocular, neurological, and behavioral features.
Pathogenic or likely pathogenic NF1 variants were detected in 71.6% (68/95) of patients; 20 pathogenic variants were not previously reported, indicating that Chinese NF1 patients are still understudied. Parental Sanger sequencing confirmation revealed 77.9% of de novo variants, a percentage that was much higher than expected. The presence of a higher number of NF1-related features at young ages was correlated with positive diagnostic findings. In addition to CALMs, neurological and behavioral features had a high expression among Chinese NF1 children. We attempted to correlate short stature with the locations of the pathogenic variants across the NF1 gene. It is interesting to notice that variants detected in the C-terminal region of the NF1 gene were less likely to be associated with short stature among the NF1 patients, whereas variants at the N-terminal were highly penetrant for the short stature phenotype.
Novel NF1 pathogenic variants are yet to be uncovered in under-studied NF1 patient populations; their identification will help to reveal novel genotype-phenotype correlations.

Neurofibromatosis 1 (NF1) is a common autosomal dominant condition caused by mutations in the NF1 gene. The appearance of multiple café-au-lait macules is an early sign of the condition, which often alert physicians to follow up and further examine the patient for the possibility of NF1. In order to determine the predictive value of multiple café-au-lait macules at early age for NF1 in Chinese patients, we recruited 19 children who shared the common sign of multiple café-au-lait macules from a general pediatric clinic in Shanghai. All the patients were clinically evaluated following the National Institutes of Health criteria for NF1 and molecular tested for sequence variants and copy number changes. Nine children met the clinical diagnostic criteria of NF1, and molecular tests confirmed all nine patients with pathogenic variants including two genomic deletions, two novel frame-shift variants, four novel nonsense and a splicing variants. In addition, four children who did not meet the diagnostic criteria were also found to carry pathogenic NF1 variants. Overall, 68.4% (13/19) of children with café-au-lait macules and various other clinical presentations were molecularly confirmed with NF1. This study demonstrated that the majority of Chinese children with multiple café-au-lait macules who came to seek for medical attention had NF1. Molecular testing is necessary to be used as an adjunct and sometimes as the main tool for confirming and diagnosing children of NF1 at early age.