Fanconi Anaemia associated with café au lait spots: A rare case report.

Fanconi Anaemia is an autosomal recessive disorder, which is characterised by progressive pancytopenia, café au lait spots (>50%), bruising, petechie, recurrent infections, short height (50%), and thumb and radial bone anomalies (40%). Herein, is presented a case of a lean emaciated female child, who presented with the chief complaints of fever, loose stools and decreased appetite for one month reported at Sindh Government General Hospital, Karachi, on February, 1, 2023. She had cutaneous findings of hyperpigmentation and café au lait spots and a tri-phalangeal thumb. On investigation, pancytopenia and a low reticulocyte count of 0.7% was also observed. Karyotype and chromosomal breakage test induced by Diepoxybutane confirmed her as a case of Fanconi Anaemia.

The treatment of infantile giant café au lait spot using golden parameter therapy with a high fluence 1064-nm Q-switched Nd: YAG laser.

BACKGROUND: Infantile café au lait spot is a brown macule with various sizes (diameter: 0.5 cm-30 cm). Infantile giant café au lait spot (IGCALS) is a huge (diameter >20cm) irregular-shaped benign hyperpigmented skin disorder that arises in infants. There has been no clearly established laser treatment consensus for the treatment of IGCALS because infants are too fragile to receive laser treatment with long hours and broad areas along with the possibility of undesirable cosmetic results. OBJECTIVES: This study investigated the safety and efficacy of Golden Parameter Therapy (GPT) using a high fluence 1064-nm Q-switched Nd:YAG laser (QSNL) for IGCALS treatment. METHODS: This study included 24 Korean patients with IGCALS. Twenty-one patients who were treated with a 1064-nm QSNL weekly for 30-50 treatment sessions with GPT. The parameters included a spot size of 7 mm, a fluence of 2.2 J/cm2 and a pulse rate of 10 Hz with one pass using a sliding-stacking technique over the IGCALS. In control group, three patients were treated with a 532-nm picosecond laser monthly for three treatment sessions with a spot size of 3 mm, a fluence of 1 J/cm2 and a pulse rate of 2 Hz. RESULTS: After the last treatment, 21 patients with IGCALS reached the complete removal of pigmented lesions, which can be considered optimal cosmetic results without any side effects such as purpura, crust, post-inflammatory hyperpigmentation, iatrogenic punctate leukoderma, and scarring. There are no recurrences in any patients after 6-21 months' follow-up, but treatment failure occurred in three patients who were treated with 532 nm picosecond laser. CONCLUSIONS: Convincingly, we argue that early intervention before 12 months of age with GPT using a high fluence 1064 nm QSNL is a safe, applicable and effective treatment for IGCALS, minimizing side effects without any recurrences.

[Clinical and genetic analysis of three children with Legius syndrome due to variants of SPRED1 gene].

OBJECTIVE: To explore the clinical and genetic characteristics of three children with Leguis syndrome. METHODS: Three children suspected as Legius syndrome at the Henan Children's Hospital for precocious puberty or short stature from June 6, 2019 to August 25, 2022 were selected as the study subjects. Clinical data of the children were collected. All children were subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing. RESULTS: All of the children (including 2 females and 1 male, and aged 4 years and 6 months, 8 years, and 14 years and 8 months, respectively) had typical café de lait spots. Child 1 also had precocious puberty, and children 2 and 3 had short statures. Genetic testing revealed that all of them had harbored heterozygous variants of the SPRED1 gene, including c.751C>T (p.Arg251Ter194) in child 1, c.229A>T (p.Lys77Ter368) in child 2, and c.1044_1046delinsC (p.R349fs*11) in child 3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.751C>T (p.Arg251Ter194) variant was predicted to be likely pathogenic, whilst the other two were known pathogenic variants. CONCLUSION: All of the three children were diagnosed with Leguis syndrome due to variants of the SPRED1 gene, which had manifested as multiple café de lait spots in conjunct with precocious puberty or short statures.

Jaffe-Campanacci syndrome; a case series and review of the literature.

BACKGROUND: Jaffe-Campanacci syndrome is a rare syndrome, characterized by multiple non-ossifying fibromas (NOF) and cafe-au-lait patches. The name was coined in 1982 by Mirra after Jaffe who first described the case in 1958. Although it's suggested there is a relation with Neurofibromatosis type 1, there is still no consensus on whether Jaffe-Campanacci syndrome is a subtype or variant of neurofibromatosis-1(NF-1). CASE PRESENTATION: In this article, we present a case series of 2 patients. The first case is a 13-year-old male with Jaffe-Campanacci syndrome who presented with a distal femur fracture. His father had positive features of both Jaffe-Campanacci syndrome and NF-1, while his sister only had features of NF-1, so we presented both. CONCLUSION: Jaffe-Campanacci has a clear relationship with type 1 neurofibromatosis, which still has to be genetically established. Due to the presence of several large non-ossifying fibromas of the long bones, it is linked to a significant risk of pathological fractures. We concur with previous authors, that an osseous screening program should be performed for all patients with newly diagnosed type 1 neurofibromatosis, to identify non-ossifying fibromas and assess the potential for pathological fracture. Moreover, siblings of patients with NF-1 should be screened for multiple NOFs that may carry a high risk of pathological fractures.

The 730 nm picosecond titanium sapphire laser for treatment of café-au-lait macules in all skin types.

OBJECTIVES: Café-au-lait macules (CALM) are benign birthmarks presenting as uniformly pigmented, well demarcated, brown patches that can be distressing to patients, especially when located in cosmetically sensitive areas. As with all pigmentary lesions in skin of color patients, CALMs have been particularly challenging to treat. Here we present the first case series characterizing treatment parameters and clinical outcomes utilizing the 730-nm picosecond titanium sapphire laser for the treatment of CALMs. This device provides an additional safe and effective treatment option for these challenging cases. METHODS: We performed a retrospective review of patients treated at a single institution between April 2021 and December 2023. Clinical photographs were graded by 3 outside board-certified dermatologists using a 5-point visual analog scale. RESULTS: Fourteen patients (age range: 10 months-66 years, mean age: 27.4 years, Fitzpatrick skin types II-VI) were treated for CALM on the face (11) or body (3). On average, patients received 4.3 treatments, with treatment intervals ranging from 4 to 40 weeks. Treatment remains ongoing with the 730-nm picosecond laser for eight patients. Overall, patients were rated to have a mean improvement of 26%-50%. Two patients (FST III and VI) achieved 100% clearance after 4-5 treatment sessions. Our study included four patients whose CALM were of the smooth bordered "coast of California" subtype, three of whom had a mean improvement rating of only 1%-25%. The fourth patient had near complete resolution. Follow up for these patients has ranged from 6 weeks to 1.5 years. Of the patients treated, one patient experienced transient post-inflammatory hyperpigmentation and another transient post-inflammatory hypopigmentation, while a third patient experienced mild persistent guttate hypopigmentation. Three patients experienced partial recurrence indicating that maintenance treatments may be needed in some patients. CONCLUSION: The 730-nm picosecond titanium sapphire laser is a safe and efficacious treatment option, in the right morphologic setting, to improve the cosmetic appearance of CALMs in a wide range of ages and skin types. To our knowledge, this is the first reported treatment of CALMs with picosecond lasers in FST V and VI patients. Our study also supports prior studies which have found that CALM with smooth-bordered "coast of California" morphology have a poor response to laser therapy as compared to those with jagged or ill-defined bordered "coast of Maine" morphology.

Novel variants in TNRC6B cause global developmental delay with speech and behavioral abnormalities, short stature, low body weight, café-au-lait spots, and metabolic abnormality.

BACKGROUND: TNRC6B deficiency syndrome, also known as global developmental delay with speech and behavioral abnormalities (MIM 619243), is a rare autosomal dominant genetic disease mainly characterized by facial dysmorphism, developmental delay/intellectual disability (DD/ID), speech and language delay, fine and motor delay, attention deficit and hyperactivity disorder (ADHD), and variable behavioral abnormalities. It is caused by heterozygous variant in the TNRC6B gene (NM_001162501.2, MIM 610740), which encodes the trinucleotide repeat-containing adaptor 6B protein. METHODS: In this study, two Chinese patients with TNRC6B deficiency syndrome were recruited, and genomic DNA extraction from peripheral blood leukocytes of these parents and their family members was extracted for whole-exome sequencing and Sanger sequencing. RESULTS: Here, we report two unrelated Chinese patients diagnosed with TNRC6B deficiency syndrome caused by novel de novo likely pathogenic or pathogenic TNRC6B variants c.335C>T (p.Pro112Leu) and c.1632delC (p.Leu546fs*63), which expands the genetic spectrum of TNRC6B deficiency syndrome. The clinical features of the patients were DD/ID, delayed speech, ADHD, behavioral abnormalities, short stature, low body weight, café-au-lait spots, metabolic abnormalities, and facial dysmorphism including coarse facial features, sparse hair, frontal bossing, hypertelorism, amblyopia, strabismus, and downslanted palpebral fissures, which expands the phenotype spectrum associated with TNRC6B deficiency syndrome. CONCLUSION: This study expands the genotypic and phenotypic spectrum of TNRC6B deficiency syndrome. Our findings indicate that patients with TNRC6B deficiency syndrome should be monitored for growth and metabolic problems and therapeutic strategies should be developed to address these problems. Our report also suggests the clinical diversity of TNRC6B deficiency syndrome.

[Research progress on the pathogenic mechanisms, diagnosis and treatment of McCune-Albright syndrome].

McCune-Albright syndrome is a rare chimeric disorder due to mutations in the postzygotic GNAS gene. It belongs to the group of guanine nucleotide-binding protein diseases, affecting a wide range of individuals. It is characterized by fibrous dysplasia, café-au-lait skin macules, and precocious puberty with other variable clinical manifestations. At present, there are difficulties in the molecular diagnosis of McCune-Albright syndrome, and there is a lack of effective clinical treatments to halt or reverse the course and regression of the disease. This article summarizes the clinical manifestations, diagnosis, pathogenic molecular mechanisms, treatment and relevant fertility guidelines of McCune-Albright syndrome, with a view to further research and therapy of McCune-Albright syndrome.

Epilepsy in Legius syndrome: Coincidence or causation?

Legius syndrome is a rare genetic disorder, caused by heterozygous SPRED1 pathogenic variants, which shares phenotypic features with neurofibromatosis type 1 (NF1). Both conditions typically involve café-au-lait macules, axillary freckling, and macrocephaly; however, patients with NF1 are also at risk for tumors, such as optic nerve gliomas and neurofibromas. Seizure risk is known to be elevated in NF1, but there has been little study of this aspect of Legius syndrome. The reported epilepsy incidence is 3.3%-5%, well above the general population incidence of ~0.5%-1%, but the few reports in the literature have very little data regarding epilepsy phenotype. We identified two unrelated individuals, both with Legius syndrome and epilepsy, and performed thorough phenotyping. One individual's mother also had Legius syndrome and now-resolved childhood epilepsy, as well as reports of more distant relatives who also had multiple café-au-lait macules and seizures. Both probands had experienced childhood-onset focal seizures, with normal brain MRI. In one patient, EEG later showed apparently generalized epileptiform abnormalities. Based on the data from this small case series and literature review, seizure risk is increased in people with Legius syndrome, but the epilepsy prognosis appears to be generally good, with patients having either self-limited or pharmacoresponsive courses.

Genetically confirmed coexistence of neurofibromatosis type 1 and Cherubism in a pediatric patient.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder typified by various combination of numerous Café-au-lait macules, cutaneous and plexiform neurofibromas, freckling of inguinal or axillary region, optic glioma, Lisch nodules and osseous lesions. Cherubism is a rare genetic syndrome described by progressive swelling of the lower and/or upper jaw due to replacement of bone by fibrous connective tissue. Patients are reported in the literature with NF1 and cherubism-like phenotype due to the NF1 osseous lesions in the jaws. The purpose of this case report is the description of a young male genetically diagnosed with both NF1 and cherubism. METHODS AND RESULTS: A 9 years and six month old patient with clinical findings of NF1 and cherubism in whom both diseases were genetically confirmed, is presented. The patient was evaluated by a pediatrician, a pediatric endocrinologist, an ophthalmologist, and an oral and maxillofacial surgeon. A laboratory and hormonal screening, a histological examination, a chest X-ray, a magnetic resonance imaging (MRI) of the orbit and a digital panoramic radiography were performed. Genetic testing applying Whole Exome Sequencing was conducted. CONCLUSIONS: A novel and an already reported pathogenic variants were detected in NF1 and SH3BP2 genes, respectively. This is the first described patient with coexistence of NF1 and cherubism. The contribution of Next Generation Sequencing (NGS) in gene variant identification as well as the importance of close collaboration between laboratory scientists and clinicians, is highlighted. Both are essential for optimizing the diagnostic approach of patients with a complex phenotype.

Treatment With Selumetinib for Café-au-Lait Macules and Plexiform Neurofibroma in Pediatric Patients With Neurofibromatosis Type 1.

This case report describes 4 patients with a rare autosomal dominant multisystem disorder resulting from NF1 variants that leads to café-au-lait macules and neurofibromas.

Pathogenesis and treatment of a giant occipital bone defect with meningoencephalocele in an NF1 child: case report and review of the literature.

Autosomal dominantly inherited neurofibromatosis type I (NF1) is a systemic disorder caused by a mutation of a gene on chromosome 17q11.2 and characterized by multiple café-au-lait spots, lentiginous macules, Lisch nodules of the iris, and tumors of the nervous system. Bony manifestations such as scoliosis, dysplasia of the greater sphenoidal wing, tibial pseudoarthrosis, short stature, and macrocephaly have been reported in approximately 50% of patients. However, calvarial bone defects are rare. After screening 324 articles, 23 cases (12 adult and 11 pediatric patients) of occipital bone defects in NF1 patients were selected. All patients had a single/multiple bone defect over the lambdoid suture. Adjacent benign plexiform neurofibromas were observed in 14 patients (60.8%, 7 adults and 7 children); one adult patient was diagnosed with neurofibrosarcoma. Meningoencephalocele over the occipital defect was noted in 8 cases (34.78%, all adults). Cranioplasty was performed in only 17.39% of patients. Histologic examination was performed in 7 of the 15 patients with associated neurofibromas/neurofibrosarcomas. Biopsy of the bone margins surrounding the defect was performed in only one case. Pathologic examination of the herniated parieto-occipital or cerebellar tissue was not performed in any of the patients studied. We report the case of a 9-year-old girl with NF1 and a significant occipital bone defect and performed a systematic review of the relevant literature to highlight the challenges in treating this condition and to investigate the underlying mechanisms contributing to bone defects or dysplasia in NF1.

Reflectance confocal microscopy as a complementary diagnostic tool for greyish-brown dermatoses in children.

Mastocytosis, lichen planus pigmentosus (LPP), fixed drug eruption (FDE) and café-au-lait macules (CALM) have a similar appearance, often lead to misdiagnosis and missed diagnoses. At the outpatient clinic at Tianjin Children's Hospital in 21 patients with mastocytosis, 18 with LPP, 11 with FDE and 12 with CALM we evaluated the characteristics and distinguishing features of their dermatoses using reflectance confocal microscopy (RCM). In mastocytosis, the dermal papillary rings generally had a significantly increased bright refractive index and the superficial dermis was filled with moderate refractive flocculent material. In LPP, the dermal papillary rings were absent and numerous different-sized cellular structures were densely distributed in the superficial dermis. In FDE, the dermal papillary rings were intact with a significantly increased bright refractive index. In CALM, normal dermal papillary rings were detected with a uniformly slightly increased refractive index and no obvious abnormality in the superficial dermis. RCM allows for real-time visualization of the major key diagnostic and distinguishing features of four greyish-brown dermatoses in children.

Clinical signs and genetic evaluation of patients with neurofibromatosis type 1 with and without optic pathway gliomas in a center in Turkey.

PURPOSE: Optic pathway gliomas (OPGs) occur in 15% of patients with neurofibromatosis type 1 (NF1). Their location renders biopsy or surgical resection difficult because of the risk of vision loss. Therefore, only a few NF1-OPGs have been used for tissue diagnosis, and only a few analyses have been published on the molecular changes that drive tumorigenesis. METHODS: Due to this reason, we evaluated 305 NF1 patients, 34 with OPG and 271 without OPG for germ line mutations. All subjects underwent clinical examination and DNA analysis of NF1, confirming the diagnosis of NF1. RESULTS: Clinically, the group with OPG had a significantly higher incidence of bone dysplasia (P < 0.001) and more café-au-lait spots (P = 0.001) compared to those in the group without OPG. The frequency of Lisch nodules was on the borderline of statistical significance (P = 0.058), whereas the frequency of neurofibromas did not differ significantly (cutaneous, P = 0.64; plexiform, P = 0.44). Individuals with OPG mostly had mutations in the first one-third of the NF1 gene compared with that in patients who did not have OPG. Some identical mutations were detected in unrelated families with NF1-OPG. CONCLUSION: The observation of certain phenotypic features and the correlation between genotype and phenotype might help to determine the risk of developing OPG with NF1.

Neurofibroma: Case Series with Clinical Features and Recommendations.

Neurofibroma is an autosomal benign disorder. It can be localized, diffuse or invasive like plexiform neurofibroma that involves the nerves, muscle, tissues, skeleton. It represents itself as a destructive variant of neurofibroma, mostly present as orbital or periorbital neurofibroma or may be associated with autosomal dominant disease. Clinical diagnosis of neurofibromatosis (NF) according to National Institutes of Health (NIH) criteria should have more than two of the seven features including lisch nodules, cafe'- au-lait spots, plexiform neurofibroma, optic glioma, freckling, first degree relative with NF or dysplasia of cortical bones. However, proper early diagnosis is still crucial due to its various presentation such as cheek mass, painless swelling on skin, chalazion, intratracheal tumor, genital swelling or ptosis. It is reported that neurofibroma often represents as ocular or facial swelling. Here we are presenting features of neurofibroma of eight cases of patients from Civil Hospital, Karachi. These cases had main complain of overhanging skin mass mainly on orbital or periorbital region that damage the area and with poor daily activities. Multiple nodules on face and body along with them Cafe'-au-lait spots and lisch nodules were main signs. While, other signs i.e. ptosis, pterygium, telecanthus and muddy discoloration of conjunctiva need further evaluation for correlation with neurofibromatosis. Debulking surgery was planned for most of the cases but the huge disfigurement caused by overhanging skin mass and nodules made it a challenge for plastic surgeons to provide good outcomes with minimum damage. Keywords: neurofibroma; lisch nodules; ptosis; Cafe'-au-lait spot; periorbital; overhanging skin.

[McCune-Albright syndrome: a case report and literature review]. / Syndrome de McCune-Albright : à propos d'un cas et revue de la littérature.

McCune-Albright syndrome is an inherited disease characterized by the association of fibrous dystrophy of bone, café-au-lait skin spots and precocious puberty revealing endocrine hyperactivity. Genetically, this disease is due to a mutation of the Gs protein responsible for activation of adenylate cyclase with excessive production of cAMP. The particular morphology of café-au-lait spots should suggest early diagnosis. Its treatment depends on the endocrinopathy from which the patient suffers and the extent of the fibrous dysplasia. Bisphosphonates have proven their effectiveness on bone pain and the limitation of fibrous dysplasia. Surgery retains its place in complicated forms. We report a rare case of McCune-Albright syndrome complicated by a femur fracture in a 12-year-old girl and we discuss the clinical and paraclinical characteristics of this pathological entity.

[Analysis of clinical features and variants of NF1 gene in 12 patients with Neurofibromatosis type 1].

OBJECTIVE: To explore the types of NF1 gene variants and clinical characteristics among patients with Neurofibromatosis type I (NF1). METHODS: Clinical data of 12 patients diagnosed at Ningbo Women and Children's Hospital between December 2019 and May 2022 were retrospectively analyzed. The probands and their family members were subjected to high-throughput sequencing, and candidate variants were verified by Sanger sequencing and chromosome microarray analysis. RESULTS: The 12 patients had ranged from 4 months to 27 years old, with a male-to-female ratio of 2 : 1. Cafè-au-lait spots were found in all patients. 83.3% of them also had axillary and/or inguinal freckling, 58.3% had neurofibromas, and 16.7% had congenital pseudarthrosis of the tibia. Five types of NF1 gene variants were identified in the patients, including 5 nonsense variants, 4 frameshift variants, 1 missense variant, 1 splice variant, 1 large deletion involving the whole gene. Six patients were found to harbor de novo variants, 2 had inherited the variants from their parents, and 4 were not verified for their parental origin. The c.3379del (p.Thr1127Glnfs*15) and c.6628_6629del (p.Glu2210Thrfs*10) variants were unreported in literature and databases. CONCLUSION: Most NF1 patients may present with Cafè-au-lait spots initially and are due to pathogenic variant of the NF1 gene. High-throughput sequencing can efficiently identify such variants among the patients and enable the definite diagnosis.

[Analysis of a child with Verheij syndrome due to variant of PUF60 gene].

OBJECTIVE: To explore the clinical phenotype and genetic variant in a child with Verheij syndrome (VRJS). METHODS: A child who had presented at the Soochow University Affiliated Children's Hospital and Wujiang District Children's Hospital in July 2022 for "elevated scapula since early childhood" was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child had manifested elevated scapulae, torticollis, neck asymmetry, facial dysmorphism, dispersed café-au-lait spots, limited mobility of upper limbs and shoulder joints, and intellectual disability. Sequencing revealed that he has harbored a de novo heterozygous c.405dupT (p.Ile136Tyrfs*4) variant of the PUF60 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PVS1+PS2_moderate+PM2_supporting). Combined his clinical features and result of genetic testing, the child was diagnosed with VRJS due to variant of the PUF60 gene. CONCLUSION: The clinical manifestations of VRJS include facial dysmorphism, intellectual disability, elevated scapulae, vertebral fusion, other skeletal malformations, without significant abnormalities of the heart, kidney, and eyes, which need to be distinguished from Klippel-Feil syndrome. Above finding has expended the mutation spectrum of the PUF60 gene and provided a reference for delineation of the genotype-phenotype correlation of the VRJS.

Clinical, Radiologic, and Histopathologic Features that Distinguish a Pigmented Plexiform Neurofibroma from a Congenital Melanocytic Nevus.

A 13-year-old Hispanic boy with no significant medical etymology presented with a chief complaint of widespread brown macules and patches. He had a large and evenly pigmented brown patch, with a centrally located 2.2 cm × 1.2 cm soft and darkly pigmented plaque, which became more apparent with tension applied to the surrounding skin (Figure 1). The patient's mother stated that the plaque was present since birth and had increased in size over time. The clinical differential diagnoses included a congenital melanocytic nevus (CMN), a large café au lait macule (CALM), and a Becker's nevus with a congenital smooth muscle hamartoma.

Case Report: Severe McCune-Albright syndrome presenting with neonatal Cushing syndrome: navigating through clinical obstacles.

Background: Café-au-lait skin macules, Cushing syndrome (CS), hyperthyroidism, and liver and cardiac dysfunction are presenting features of neonatal McCune-Albright syndrome (MAS), CS being the rarest endocrine feature. Although spontaneous resolution of hypercortisolism has been reported, outcome is usually unfavorable. While a unified approach to diagnosis, treatment, and follow-up is lacking, herein successful treatment and long-term follow-up of a rare case is presented. Clinical case: An 11-day-old girl born small for gestational age presented with deterioration of well-being and weight loss. Large hyperpigmented macules on the trunk, hypertension, hyponatremia, hyperglycemia, and elevated liver enzymes were noted. ACTH-independent CS due to MAS was diagnosed. Although metyrapone (300 mg/m2/day) was started on the 25th day, complete remission could not be achieved despite increasing the dose up to 1,850 mg/m2/day. At 9 months, right total and left three-quarters adrenalectomy was performed. Cortisol decreased substantially, ACTH remained suppressed, rapid tapering of hydrocortisone to physiological dose was not tolerated, and supraphysiological doses were required for 2 months. GNAS analysis from the adrenal tissue showed a pathogenic heterozygous mutation. During 34 months of follow-up, in addition to CS due to MAS, fibrous dysplasia, hypophosphatemic rickets, and peripheral precocious puberty were detected. She is still regularly screened for other endocrinopathies. Conclusion: Neonatal CS due to MAS is extremely rare. Although there is no specific guideline for diagnosis, treatment, or follow-up, addressing side effects and identifying treatment outcomes will improve quality of life and survival.

[MULTIPLE CAFÉ-AU-LAIT MACULES AND INTERTRIGINOUS FRECKLING: BEYOND THE RASOPATHIES].

INTRODUCTION: Piebaldism is the dominantly inherited skin disorder clinically characterized by congenital stable and well circumscribed patches of leukoderma (depigmented skin) of ventral distribution, involving central forehead, frontal chest and abdomen and central portion of limbs, and by localized poliosis (white hair). Inherited or de novo mutations in proto-oncogene KIT, encoding the transmembrane tyrosine kinase receptor c-kit, underly the majority of piebaldism cases. Piebaldism is a disorder characterized by incomplete penetrance and variable expressivity.