Au Lait Spots Research Articles

Three case reports of patients indicating the diversity of molecular and clinical features of 16p11.2 microdeletion anomaly

Background16p11.2 microdeletion is a known chromosomal anomaly associated mainly with neurocognitive developmental delay, predisposition to obesity, and variable dysmorphism. Although this deletion is relatively rare among the general population, it is one of the serious known genetic aetiologies of obesity and autism spectrum disorder.Case presentationThis study presents three cases of deletions within the 16p11.2 region. Every child had mild variable craniofacial abnormalities, hand or foot anomalies and developmental and language delays. The first proband had obesity, epilepsy, moderate intellectual disability, aphasia, motor delay, hyperinsulinism, and café au lait spots. The second proband suffered from cardiac, pulmonary, and haematological problems. The third proband had motor and language delays, bronchial asthma, and umbilical hernia. Although each patient presented some features of the syndrome, the children differed in terms of their clinical pictures. Genetic diagnosis of 16p11.2 microdeletion syndrome was made in children at different ages based on multiplex ligation probe-dependent amplification analysis and/or microarray methods.ConclusionsOur reports allow us to analyse and better understand the biology of 16p11.2 microdeletion throughout development. However, the variability of presented cases supports the alternate conclusion to this presented in available literature regarding 16p11.2 deletion, as we observed no direct cause-and-effect genotype/phenotype relationships. The reported cases indicate the key role of the interdisciplinary approach in 16p11.2 deletion diagnostics. The care of patients with this anomaly is based on regular health assessment and adjustment of nervous system development therapy.

Managing Chronic Health Needs in Child Care and Schools—Neurofibromatosis (NF) and Tuberous Sclerosis Complex (TSC)

Patient Education| 2021 Managing Chronic Health Needs in Child Care and Schools—Neurofibromatosis (NF) and Tuberous Sclerosis Complex (TSC) Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Share Icon Share Facebook Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Managing Chronic Health Needs in Child Care and Schools—Neurofibromatosis (NF) and Tuberous Sclerosis Complex (TSC). Pediatric Patient Education 2021; 10.1542/ppe_document128 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All AAP SitesAll PublicationsPediatric Patient Education Search Advanced Search Subjects: Managing Chronic Health Needs in Child Care There are many types of neurocutaneous syndromes (syndromes that include skin findings). The most common is neurofibromatosis (NF). There are 7 types of NF. Although they are all different, they all have skin and neurologic findings. Neurofibromatosis type 1 (NF1) is the most common type, and, while it is inherited, half of the cases are new mutations. Tuberous sclerosis complex (TSC) is less common but can involve seizures, lesions on the face, and learning difficulties. Half of children with TSC have normal intelligence and a third have profound intellectual disabilities. Neurofibromatosis type 1 occurs at approximately 1 in 3,500 births in the United States; TS, at approximately 1 in 6,000. Neurofibromatosis type 1: The findings and the course of the condition vary greatly. Children with NF1 are often born with many light-brown birthmarks, called café au lait spots, or the spots... © 2019 American Academy of Pediatrics. All rights reserved. You do not currently have access to this content.

The Patients' Experiences of Burden of Neurofibromatosis: A Qualitative Study.

Background:Neurofibromatosis Type 1 (NF1) is a common autosomal disorder; the criteria for the diagnosis of NF1 includes café au lait spots, freckling, and Neurofibromas (NF). Skin symptoms have a major impact on patients' Quality of Life (QOL) but little is known about the burden of the disease on patients. The aim of this study was to explore the experiences of patients with NF.Materials and Methods:Using purposive sampling, 20 participants were enrolled in this qualitative content analysis study. The study was carried out between 2019 and 2020. Unstructured interviews and field notes were used to gather data. Data collection was stopped when data saturation was achieved.Results:Data analysis revealed 14 subcategories and 4 categories including “failing and falling behind in life”, “deprivation and restriction”, “social isolation”, and “ineffective adaptation to the disease”, which indicate the perception of patients with NF.Conclusions:In addition to the physical burden due to physical complications and problems, NF imposes a high degree of psychological and social burden on patients causing mental conflicts, which in turn results in them failing and falling behind in life. These findings illustrate the need to develop strategies and use multidisciplinary approaches to support patients, and thus to reduce the burden of NF.

A Case of Solitary Neurofibroma of the Cheek

Neurofibroma is a benign peripheral nerve sheath tumor consisting of an admixture of Schwann cells, fibroblasts, perineurial-like cells, and axons. It is usually considered as a part of neurofibromatosis type-1 （von Recklinghausen disease）. Solitary neurofibroma is an uncommon tumor of the oral and maxillofacial region. A man in his 40s was referred to our hospital with the chief complaint of a mass in the right cheek. Physical examinations revealed a well-defined, elastic-soft, mobile, painless 25-mm mass in the cheek. Ultrasonography revealed a hyperechoic mass with clear borders, internal nonuniformity, and a low blood flow signal. Magnetic resonance imaging revealed that the mass was adjacent to the masseter muscle, and had a relatively homogenous and equal signal intensity with the muscle on T1-weighted image, and high signal intensity on T2-weighted image. The tumor was surgically resected under general anesthesia. Microscopic examination showed random rearrangement of spindle cell proliferation, and positive immunostaining for the S-100 protein and CD34. The tumor was diagnosed as a neurofibroma. Neither café au lait spots nor other tumors were observed on physical examination. The final diagnosis was solitary neurofibroma arising in the cheek. Three years after the surgery, the patient showed no signs of tumor recurrence.

Optic nerve glioma in neurofibromatosis: Radiological clues to diagnosis in a young child

ABSTRACTA 13-month-old boy presented with delay in attainment of milestones. On examination, he had café au lait spots and central hypotonia. MRI brain with contrast revealed bilateral bulky enhancing optic nerves with involvement of chiasma. Mid-orbit downward kinking and pseudo-cerebrospinal fluid sign classical of optic nerve glioma (OPG) with neurofibromatosis1 (NF1) could be well appreciated in the MRI. Correct identification of OPG may help in the diagnosis of NF1 in a young child, as other phenotypic features appear later in childhood.

Pediatric case of bilateral tibia varum with pseudoarthrosis and macrocephaly-primary report

This report describes a case study of a two and half years old male child with bilateral tibia varum and non-united fracture at the left tibia, referred for Physiotherapy. He was a term child, born to a NCM couple with no neurological complications. No history of early sepsis or systemic complications were reported. All milestones were attained in time. Child had age related social and communication skills. On evaluation, he has Macrocephaly, multiple cafe au lait spots, freckles at groin and axilla. This case was diagnosed as Neurofibromatosis Type 1. Physiotherapy objectives and plans are described and are open for discussion.

Neurofibromatosis: A Genetic Disorder of Nervous System

Neurofibromatosis is a hereditary issue of the sensory system. Tumors structure on your nerve tissues. Predominantly, neurofibromatosis problems influence the development and improvement of nerve cell tissue. The problems are known as neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). NF1 is the more normal kind of neurofibromatosis. Schwannomatosis has as of late been recognized as a third and more uncommon sort of neurofibromatosis, however specialists don’t think a lot about it yet. You may likewise hear NF1 called Recklinghausen sickness, von Recklinghausen illness, von Recklinghausen’s phakomatosis, von Recklinghausen’s neurofibromatosis, neurofibroma (various), neurofibromatosis-pheochromocytoma-duodenal carcinoid condition, or fringe neurofibromatosis. It causes numerous bistro au lait spots (patches of tan or light earthy colored skin) and neurofibromas (delicate, beefy developments) on or under your skin. It can likewise cause extended or distorted bones and ebb and flow of the spine (scoliosis). Incidentally, tumors may create in the mind, on cranial nerves, or on the spinal rope. About half to 75% of individuals with NF1 likewise have learning inabilities. NF2 is likewise called two-sided acoustic neurofibromatosis, vestibular schwannoma neurofibromatosis, or focal neurofibromatosis. It’s substantially less basic than NF1 and is portrayed by numerous tumors on the cranial and spinal nerves. Tumors that influence both of the hear-able nerves and hearing misfortune starting in the youngsters or mid 20s are by and large the primary indications of NF2.

Fibrous Dysplasia of the Spine-A Case Involving the Polyostotic Form Isolated to the Thoracolumbar Spine.

Fibrous dysplasia of the spine in a polyostotic form is very rare, with fewer than 36 cases discussed in the literature and there is no such case in Indonesia that has been reported. The aim of this report is to present a case from Indonesia of polyostotic fibrous dysplasia isolated in the spine. We report a case of a 38-year-old Sundanese man with a 1-year history of progressive back pain and weakness of both lower extremities. There was no history leading to infection and no previous trauma. A physical examination revealed kyphoscoliotic deformity, a café au lait spot, tenderness at the thoracolumbar region, and neurological deficits. Laboratory studies were within normal ranges. Plain radiographs showed lytic lesion and kyphoscoliosis. Magnetic resonance imaging showed an endosteal scalloping, infiltrative process, expansion, and destruction in the vertebral bodies from T2 to L5. The findings of an aggressive destructive process was highly suspicious of a malignant process, relying on differential diagnosis and metastases, plasma cell myeloma, bone tumor and chronic infectious spondylitis. Histology revealed an irregularly oriented osteoid without osteoblastic rimming but surrounded by fibroblastic proliferation with a C-shaped sign. Investigations revealed a diagnosis of polyostotic fibrous dysplasia of the thoracolumbar spine in isolation. The patient underwent T5-S1 stabilization and bone grafting. At 1 year postoperative, the patient was asymptomatic; there was no recurrence and minimal neurological deficit with grade II on the modified McCormick scale. A case of the polyostotic form of fibrous dysplasia of the spine in isolation has never been reported in Indonesia. The extreme rarity of this type of presentation can pose a diagnostic dilemma, and in cases isolated to the spine, surgical treatment with posterior stabilization, decompression, and bone grafting gives a good functional outcome.

Paediatric Extensive Cervical Plexiform Neurofibroma Mimicking a Parotid Lesion

Neurofibromatosis Type 1 (NF1), also known as von Recklinghausen’s disease is a multisystem genetic disorder that occurs with an incidence of 1 in 4000 live births. Plexiform nmeurofibroma (PN) is a rare important variant of NF1, seen in 5 to 15% of cases. We report a 7-year-old boy, without family history of neurofibromatosis presented with left neck swelling associated with multiple café au lait spots for one-year duration. Computed tomography of head and neck revealed an extensive soft tissue lesion involving the left parapharyngeal, carotid space and parotid space encasing the left internal and common carotid artery until its origin at the arch of aorta with erosion of the basiocciput. He underwent transcervical excision of the lesion, which was confirmed histopathologically as PN.

McCune Albright Syndrome: A Case Report

McCune Albright syndrome (MAS) is a very rare genetic disease characterised by any two of the following three findings: café au lait spots, polyosteotic fibrous dysplasia and endocrine disorders. The clinical presentation of MAS may vary depending on which of the various components of the syndrome predominate. Here, we report one case of MAS presenting with precocious puberty.

Diagnosis of congenital pigmented macules in infants with reflectance confocal microscopy and machine learning

To the Editor: Congenital pigmented macules (CPMs) can be clinically and dermoscopically equivocal in infants, making the differential diagnosis between café au lait spots (CLSs) and congenital melanocytic nevus (CMN) difficult. Reflectance confocal microscopy (RCM) may reveal morphologic patterns, differentiating CMN from CLS at the bedside and changing management and follow-up of these lesions.

Café Au Lait Spot is Marker for Pheochromocytoma in Hypertensive Crisis With a Wide-Differential Diagnosis: A Case Report

Café Au Lait Spot is Marker for Pheochromocytoma in Hypertensive Crisis With a Wide-Differential Diagnosis: A Case Report

Genetic analysis of a child with global developmental delay and neurofibromatosis type 1

To explore the genetic basis for a child with global developmental delay and neurofibromatosis type 1 (NF1). The patient underwent clinical examination. Whole exome sequencing (WES) was carried out to detect pathogenic genetic variants. The child had cafe au lait spots all over her body, pigmentation in the back, and global developmental delay as assessed by Gese II. Cranial MRI revealed globular abnormal density in the lower hemisphere of left posterior cranial fossa. WES detected a novel variant of the NF1 gene, c.6513-6515del (p.Tyr2171), which was strongly correlated with her clinical phenotype. The same variant was not found in either parent and was unreported previously. The c.3842T>G variant of the NF1 gene probably underlay the NF1 and global developmental delay in this child, for whom prompt symptomatic treatment and regular follow-up were recommended.

Hypopigmented macules in neurofibromatosis type 1: A case control study

To the Editor: Neurofibromatosis type 1 (NF1) is an autosomal dominant, neurocutaneous disorder. In most cases, cutaneous pigmentary manifestations are the main diagnostic clue. NF1 is characterized by hyperpigmentation—café au lait macules (CALMs), skinfold freckling, and melanotic plexiform neurofibromas. However, hypopigmented lesions have received little attention in patients with NF1. Riccardi1Riccardi V.M. Neurofibromatosis and Albright's syndrome.Dermatol Clin. 1987; 5: 193-203Abstract Full Text PDF PubMed Google Scholar described the presence of hypopigmented macules (HMs) in approximately 2% to 3% of patients with NF1 in 1987. Studies regarding the physiopathology of HM in NF1 are lacking. This study aimed to characterize the prevalence of HMs in our pediatric patients diagnosed with NF1. A case-control prospective study design was used to compare the prevalence of HMs in 108 patients diagnosed with NF1 (younger than 18 years) and 137 healthy age-matched control individuals. All patients included in the cases cohort had a confirmed diagnosis of NF1. We required a third National Institutes of Health criterion or genetic testing in children who exclusively showed CALMs and skinfold freckling. The patients were enrolled from October 2014 to January 2017. We also assessed the number, location, size, and morphology of HMs in our patients. Well-circumscribed lesions, those with early onset in life, and stable hypomelanosis were considered HMs. Patients with postinflammatory hypomelanosis and other possible causes of hypopigmentation as well as vitiligo or nevus anemicus (NA) were excluded. All HMs became erythematous after rubbing, unlike NA. All participants signed informed consent. We observed that 13.9% (n = 15) of patients showed HMs. In the control group 4.4% (n = 6) children presented with HMs. The prevalence of HMs in the cases group was significantly higher than in the control group (Pearson chi-square test P value = .008). Demographic and clinical characteristics are shown in Table I. The HM sizes ranged from 0.5 to 9 cm, and all presented with well-defined or sharp margins (Fig 1 and Supplemental Fig 1; available via Mendeley at https://doi.org/10.17632/6w3g76nyxr.2). Parents recalled the presence of HMs from birth in 4 (22.2%) children.Table IDemographic and clinical characteristicsClinical featuresPatients with NF1 (N = 108)Control individuals (N = 137)HMs, n (%)15 (13.9)6 (4.4)Age when HMs first noticed, y Mean4.24.7 Range0-103-13Sex, n (%)P = .132P = 1 Male9 (60)3 (50) Female6 (40)3 (50)Distribution Solitary, n (%)12 (80)6 (100) Range1-2 Mean ± SD1.2 ± 0.41Location, n (%) Thorax6 (40)3 (50) Legs5 (33.3)1 (16.6) Abdominal3 (20)0 Arms2 (13.3)1 (16.6) Lumbar1 (6.6)1 (16.6) Neck1 (6.6)0Size, cm, n (%) <14 (22.2)2 (33.3) 1-513 (72.2)4 (66.6) >51 (5.6)0Morphology, n (%) Ash-leaf6 (33.3)0 Rounded5 (27.8)3 (50) Oval5 (27.8)3 (50) Polygonal2 (11.1)0HM, Hypopigmented macule; SD, standard deviation. Open table in a new tab HM, Hypopigmented macule; SD, standard deviation. Although CALMs are present in almost all patients with NF1, the prevalence of circumscribed hypomelanosis has not been characterized. The differential diagnosis for HMs included tuberous sclerosis complex (TSC) hypomelanotic macules, NA, vitiligo, pityriasis alba, postinflammatory hypopigmentation, and piebaldism. The simultaneous occurrence of NF1 and TSC in a single individual is extremely rare,2Samanta D. Bosanko K.B. Zarate Y.A. An infant with ash-leaf and café au lait spots: a case of double phakomatosis.Acta Neurol Belg. 2016; 117: 323-324Crossref PubMed Scopus (1) Google Scholar and our patients did not show other signs of TSC. The HMs observed in patients with NF1 fulfilled the Coupe clinical diagnostic criteria and could be considered nevus depigmentosus (ND).3Coupe R.L. Unilateral systematized achromic naevus.Dermatology. 1967; 134: 19-35Crossref Scopus (40) Google Scholar,4Kim S.K. Kang H.Y. Lee E.S. Kim Y.C. Clinical and histopathologic characteristics of nevus depigmentosus.J Am Acad Dermatol. 2006; 55: 423-428Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar ND is the best characterized congenital, stable throughout life, well-circumscribed hypopigmented lesion.3Coupe R.L. Unilateral systematized achromic naevus.Dermatology. 1967; 134: 19-35Crossref Scopus (40) Google Scholar ND occurs in approximately 0.4% to 0.7% of infants,5Baselga E. Disorders of hypopigmentation.in: Schachner L.A. Hansen R.C. Pediatric Dermatology. 4th ed. Mosby Elsevier, Philadelphia, PA2012: 719-722Google Scholar so the HM prevalence in our series (13.9%) was higher than expected. Thus, our results suggest a statistical relationship between NF1 and HMs (P < .008). However, the pathophysiologic explanation of the higher prevalence of HMs in the NF1 population remains unknown. We conclude that HMs are a common finding in NF1. This finding could be either a coincidence or truly associated with NF1. Basic research investigations are needed to achieve a better knowledge of HM physiopathology.

Satisfaction from surgical treatment and its’ influence on comfort of feeling in patients with Recklinghausen disease

&lt;b&gt;Background:&lt;/b&gt; Neurofibromatosis type 1 (NF-1) is one of the most common autosomal dominant disorders. Multiple benign dermal neurofibromas, café au lait spots, axillary and inguinal freckling are the hallmarks of NF-1. &lt;br&gt;&lt;b&gt;Aim:&lt;/b&gt; The aim of this paper is to verify if surgical treatment performed in patients with NF-1 is satisfactory to them and to describe demographic factors characteristic for patients with Recklinghausen disease. &lt;br&gt;&lt;b&gt;Methods: &lt;/b&gt;A special questionnaire was prepared for the study, which contained 45 questions. Seventeen patients with neurofibromatosis type 1 agreed to fill in the questionnaire aged from 22 to 61 years. &lt;br&gt;&lt;b&gt;Results:&lt;/b&gt; Surgical treatment in patients was started between 6 and 45 years of age. All patients declared their will to continue surgical treatment. After treatment patients felt more comfortable, more self-confident and sociable. The first symptoms of neurofibromatosis were seen at about 13 years of life in most patients. All women who gave birth noticed progression of the disease during pregnancy. &lt;br&gt;&lt;b&gt;Conclusions: &lt;/b&gt;Performed surgical treatment raises life comfort and increases self-confidence in patients with neurofibromatosis type 1. Due to visible skin changes in neurofibromas it is worth referring patients to Plastic Surgery Departments. Doctors dealing with patients with NF-1 should inform them about the potential heredity of the disease and that puberty and pregnancy intensify the process of skin neurofibroma development.

Neurofibromatosis type 1 associated with hypophosphatemic osteomalacia due to hypersecretion of fibroblast growth factor 23: a case report

BackgroundNeurofibromatosis type 1 is characterized by multiple café au lait spots and cutaneous and plexiform neurofibromas, and is one of the most common autosomal dominant hereditary disorders caused by mutations of the neurofibromatosis type 1 tumor suppressor gene. Osteomalacia in neurofibromatosis type 1 is very rare and is characterized by later onset in adulthood. In humans, fibroblast growth factor 23, which is a causative factor of tumor-induced osteomalacia, is not only a paracrine and autocrine factor, but is also a physiological regulator of phosphate balance in normal serum.Case presentationOur patient was a 65-year-old Japanese woman whose neurofibromas began to appear when she was in elementary school. At age 28, she was diagnosed as having neurofibromatosis type 1. A spinal compression fracture and multiple rib fractures were identified in 2012 and 2017, respectively. Her laboratory findings revealed hypophosphatemia due to renal phosphate wasting and a high serum level of fibroblast growth factor 23. Neurofibromas located on the surface of her right forearm and left upper arm, in which a slight abnormal accumulation of tracers was observed on 111indium-pentetreotide scintigraphy, were surgically removed, but there was no improvement in hypophosphatemia or serum fibroblast growth factor 23 after surgery. Therefore, we administered eldecalcitol, which also failed to produce improvement in abnormal data. Subsequent combination with dibasic calcium phosphate hydrate led to improvement in some of the abnormalities, including hypophosphatemia. Immunohistochemical staining using anti-human fibroblast growth factor 23 antibody revealed slightly positive results, however, only one out of three amplifications of the fibroblast growth factor 23 gene was observed by real-time polymerase chain reaction, and no clear fibroblast growth factor 23 gene expression in the resected neurofibromas could be confirmed.ConclusionsWe here describe a first rare case of a 65-year-old woman with neurofibromatosis type 1 associated with hypophosphatemic osteomalacia in which a high serum fibroblast growth factor 23 level was confirmed.

SAT-073 Testicular Abnormalities in the Absence of Precocious Puberty in Mccune-Albright Syndrome

Background: Mc-Cune Albright Syndrome (MAS) is a rare disorder characterized by skeletal lesions, skin hyperpigmentation and hyperfunctioning endocrinopathies. Gonadotropin-independent precocious puberty is the most common endocrinopathy, known to be more common in females than males, but little is known about male gonadal pathology in MAS. Clinical case: 3-year-old boy presented with worsening unilateral limp and was noted to have a pathologic femoral fracture. Bone scan demonstrated extensive fibrous dysplasia in the long bones and skull base. He had a large café au lait spot on the back. He was diagnosed with MAS on clinical criteria.At 4 years of age, initial exam was normal without signs of precocious puberty. Linear growth followed the 70th percentile, on track for his genetic background (mid parental height 70th percentile). Initial hormonal work up showed normal thyroid function, prolactin, growth factors and pre-pubertal gonadotropins and testosterone.At 6 years of age, he started to demonstrate bilateral testicular enlargement of 4-6 mL with pubic hair Tanner stage I. Bone age was concordant with chronologic age. Gonadotropins and testosterone level were pre-pubertal. Testicular ultrasound showed bilateral enlargement with punctuate densities without evidence of hydrocele or mass.By 8 years of age, he had further testicular enlargement to 8 mL bilaterally, normal penile length 5.5 cm (6.2 ± 1.0) and no pubic hair. Biochemical evaluation showed normal thyroid function and pre-pubertal gonadotropins and testosterone. Repeat testicular ultrasound showed heterogeneous echotexture representing microlithiasis, without a focal mass. Conclusion: Macroorchidism can be present in the absence of gonadotropin independent precocious puberty in MAS. Testicular ultrasound evaluation is important, as hyper-hypoechoic lesions, bilateral microlithiasis, focal calcifications, are the most common testicular abnormality in males with MAS.Microlithiasis, due to calcium deposits within the seminiferous tubules, have been described often in this condition, and should be considered a marker of male MAS. The natural history of male fertility and testicular cancer risk in the context of microlithiasis and testicular calcifications is unknown. Close observation and testicular imaging at baseline and after age 5, to characterize subclinical involvement, are an appropriate course to follow.

MON-072 A 2 -Year Old Girl with Turner Syndrome and Neurofibromatosis Type 1

Introduction: Turner syndrome (TS) occurs due to loss of either all or part of the X chromosome, in some or all the cells of the body. The most consistent features of TS are short stature and premature ovarian failure. Neurofibromatosis type 1 (NF1) is an inheritable in an autosomal dominant manner tumor predisposition syndrome and is caused by loss-of-function mutations in the tumor suppressor NF1 gene (neurofibromin 1). Literature review indicated rare cases with NF1 and TS (1). We report the sixth girl with mosaic TS and NF1 who presented with optic nerve glioma. Case report: A 2-year-old female presented to us due to short stature. Her height was 2,5 SD lower than the mean parental height curve, and her bone age was delayed only by 3 months. She already had a normal (46XX) peripheral blood karyotype (70 mitoses). She had abnormal body proportions and with short limbs with unremarkable café au lait spots. Additionally, to the short stature laboratory investigation we ordered a gene panel to exclude hypochondroplasia, and a Karyotype in fibroblasts culture from oral cavity sample. The results revealed low IGF-1 and mosaic TS in 14%. We preformed 2 provocative tests which revealed low growth hormone peak < 5 ng/ml. A brain and pituitary MRI to exclude pituitary lesions or structural abnormalities revealed gliomas of the optic chiasma and the right optic nerve with characteristic NF1 “spots” (regions of signal abnormality in T2 sequences) involving the basal ganglia, cerebellum and the right temporal lobe. DNA sequencing targeted to a gene panel related to NF1 and NF2 revealed a novel de novo heterozygous NF1 gene mutation in exon 28 [3764Α>G];[=]p.[Gln1255Arg]. Discussion: NF1- Gliomas are most commonly seen in young children, (mean 4.5 years). Only 1/3 of affected children will require therapeutic intervention. However early diagnosis, of optic gliomas is important. Our patient was completely asymptomatic by the time of diagnosis and no other symptom or sign of NF1 was apparent. Ophthalmologic examination was normal, but visual electrophysiologic testing was abnormal as far the right optic nerve is concerned. The oncology team decided to preform chemotherapy. In TS impaired growth is related to resistance in GH. Some studies suggested that there could be a relationship between GHD and NF1 even in the absence of an organic pituitary damage. In our patient it has been decided not to treat with GH and closely track the patient’s growth. Conclusion: Coexistence of NF1 with TS is rare. Awareness is needed as early identification and treatment of CNS gliomas can prevent visual loss and severe co-morbidities.1.Rare Presentation of Neurofibromatosis and Turner Syndrome in a Pediatric Patient. Pediatr Rep. 2017 Jun 26; 9(2): 6810

Pediatric Lymphoma and Solid Tumors Associated With Cancer Susceptibility Syndromes.

The aim of this study was to determine cancer susceptibility syndromes (CSSs) in children with lymphoma and solid tumors and to evaluate their effects on overall survival rates. Between 2006 and 2019, the oncologic charts of 672 patients who were followed-up with a diagnosis of lymphoma and solid tumor in our clinic were retrospectively reviewed. CSSs were detected in 42 children (6.25%). The most common CSS was DNA damage repair defects/genetic instability (in 18 of 42 patients with CSSs, 42.8%). In the patients with CSSs, 48 different cancers developed. The most common types of cancer were lymphoma (n: 10, 21%) and high-grade glial tumor (n: 9, 19%). The lymphoma subgroups were very rare childhood lymphomas, such as gray zone lymphoma and marginal zone lymphoma. The overall survival rates for patients with DNA damage repair defects/genetic instability; with CSSs other than DNA damage repair defects/patients with genetic instability syndrome; and without any CSS, were 9.7%, 65.1%, and 68.7%, respectively. The overall survival rate for patients with DNA damage repair defects/patients with genetic instability syndrome was lower than both patients with CSSs other than DNA damage repair defects/genetic instability syndrome (P=0.002) and those without any CSS (P<0.0001). CSSs should be kept in mind in children with cafe au lait spots; syndromic features; a family history of cancer, especially in siblings; and rare childhood cancers.

Localized Hypertrophic Neuropathy as a Neoplastic Manifestation of KRAS-Mediated RASopathy.

Localized hypertrophic neuropathy is a rare Schwann cell proliferation that usually affects single nerves from the extremities, and it is of unclear etiology in its pure form. RASopathies are a defined group of genetic diseases with overlapping clinical features, usually secondary to germline mutations in genes encoding either components or regulators of the RAS/MAPK pathway. Herein, we report an 11-year-old boy presenting with café au lait spots and right leg length discrepancy. A fascicular nerve biopsy of the tibial nerve demonstrated a Schwann cell proliferation with prominent onion-bulb formation, satisfying criteria for localized hypertrophic neuropathy. Molecular genetic analysis demonstrated identical KRAS mutations (c38_40dupGCG) in the peripheral nerve lesion and melanocytes from café au lait spots, but not in blood, supporting a diagnosis of a KRAS-mediated rasopathy with mosaicism. Immunohistochemical staining in the peripheral nerve lesion demonstrated strong pERK staining consistent with downstream MAPK pathway activation. This report suggests that at least a subset of localized hypertrophic neuropathies are bonafide, well-differentiated Schwann cell neoplasms developing through oncogenic RAS signaling, which provides new insights into the controversial entity historically known as localized hypertrophic neuropathy.