Search

Background: Postcontrast magnetic resonance imaging (MRI), obtained under anesthesia, is often used to evaluate brain parenchymal and vascular abnormalities in young children, including those with Sturge-Weber syndrome. However, anesthesia and contrast administration may carry risks. We explored the feasibility and potential diagnostic value of a noncontrast, nonsedate MRI acquisition in Sturge-Weber syndrome children and their siblings with a wide range of cognitive and behavioral functioning. Methods: Twenty children (10 with Sturge-Weber syndrome and 10 healthy siblings; age: 0.7-13.5 years) underwent nonsedate 3-tesla (T) brain MRI acquisition with noncontrast sequences (including susceptibility-weighted imaging) prospectively along with neuropsychology assessment. All images were evaluated for quality, and MRI abnormalities identified in the Sturge-Weber syndrome group were compared to those identified on previous clinical pre- and postcontrast MRI. Results: Nineteen participants (95%) completed the MRI with good (n = 18) or adequate (n = 1) quality, including all children with Sturge-Weber syndrome and all 5 children ≤5 years of age. The Sturge-Weber syndrome group had lower cognitive functions than the controls, and both groups had several children with behavioral issues, without an apparent effect on the success and quality of the MR images. Susceptibility-weighted imaging detected key venous vascular abnormalities and calcifications and, along with the other noncontrast sequences, provided diagnostic information comparable to previous clinical MRI performed with contrast administration under anesthesia. Conclusion: This study demonstrates the feasibility and the potential diagnostic value of a nonsedate, noncontrast MRI acquisition protocol in young children including those with cognitive impairment and/or behavioral concerns. This approach can facilitate clinical trials in children where safe serial MRI is warranted. [ABSTRACT FROM AUTHOR]

People with Neurofibromatosis Type 1 (NF1) suffer disfigurement and pain when hundreds to thousands of cutaneous neurofibromas (cNFs) appear and grow throughout life. Surgical removal of cNFs under anesthesia is the only standard therapy, leaving surgical scars. Effective, minimally-invasive, safe, rapid, tolerable treatment(s) of small cNFs that may prevent tumor progression. Safety, tolerability, and efficacy of 4 different treatments were compared in 309, 2-4 mm cNFs across 19 adults with Fitzpatrick skin types (FST) I-IV: radiofrequency (RF) needle coagulation, 755 nm alexandrite laser with suction, 980 nm diode laser, and intratumoral injection of 10 mg/mL deoxycholate. Regional pain, clinical responses, tumor height and volume (by 3D photography) were assessed before, 3 and 6 months post-treatment. Biopsies were obtained electively at 3 months. There was no scarring or adverse events > grade 2. Each modality significantly (P <.05) reduced or cleared cNFs, with large variation between tumors and participants. Alexandrite laser and deoxycholate were fast and least painful; 980 nm laser was most painful. Growth of cNFs was not stimulated by treatment(s) based on height and volume values at 3 and 6 months compared to baseline. Intervention was a single treatment session; dosimetry has not been optimized. Small cNFs can be rapidly and safely treated without surgery. [ABSTRACT FROM AUTHOR]

Cobb syndrome is a rare neurocutaneous disease characterized by multiple spinal vascular anomalies and vascular skin lesions affecting the corresponding dermatome. We present a case of a 12-year-old boy with history of spinal arteriovenous malformation (AVM) extending from T4-T5 status post partial embolization 3 years ago and hyperpigmented patch overlying his thoracic back region presenting with 2 days of back pain and lower extremity numbness and weakness. He had multiple Type III AVMs within the spinal and paraspinal tissues involving the T4-T7 vertebral elements, most extensively T4 and T5. The largest aneurysm located at the confluence of the main AVM nidus was a 4 mm anterior spinal artery aneurysm, which was embolized with partial embolization of the main AVM nidus, resulting in complete aneurysm occlusion. This report provides valuable insight on the natural history, recurrence risk, and treatment options of Cobb syndrome to aid in early diagnosis and improve outcomes. [ABSTRACT FROM AUTHOR]

Background: A distally based sural flap is a workhorse flap used to reconstruct the distal lower leg and foot. It developed a bad reputation due to venous congestion, leading to flap failure. Herein, we present a new modification in the form of proximal catheterization and distal ligation of the short saphenous vein to relieve flap congestion. Methods: Twenty patients underwent reconstruction with distally based sural artery flaps for defects around the ankle, distal leg, and foot from June 2019 to March 2021. Distal ligation with proximal catheterization of the short saphenous vein was performed to reduce the risk of venous congestion. Results: Early flap congestion was observed in five flaps (25%). The venous congestion was relieved by draining congested blood through the catheter. The total amount of blood removed was around 80–100 mL in the first 2 days postoperatively. The flaps healed uneventfully as two flaps with distal 2-cm necrosis healed with dressing. Conclusions: Distal ligation of the short saphenous vein may prevent venous overloading from the foot and reduce sural flap venous congestion. Proximal catheterization of the vein to relieve flap congestion is an effective flap safety tool. Level of evidence: Level V, Risk/Prognostic. [ABSTRACT FROM AUTHOR]

Trigeminal trophic syndrome is an uncommon condition characterized by paresthesia, itch, and self-inflicted wounds following the trigeminal dermatome(s). Similar processes adhering to cervical nerve distributions have been reported, calling into question the specificity of trigeminal trophic syndrome for the trigeminal network. Herein, we report patient with trigeminal trophic syndrome adhering to the C2 dermatome, a previously unreported distribution.

Abstract Background: Nevus sebaceous of Jadassohn is defined as a rare congenital malformation characterized as a non-hereditary hamartoma of the adnexal structures of the skin. Its etiology is not yet well understood, but it is believed to be related to post-zygotic mutations in the HRAS, NRAS and KRAS genes. Objective: To describe the clinical manifestation of nevus sebaceous, as well as the main management techniques addressed in the medical literature. Moreover, the present study discusses a case report of a congenital linear nevus in the left retroauricular region found in a male patient, without extracutaneous manifestations. Method: A narrative review of the literature was carried out. Discussion: Nevus sebaceous occurs as lesions with a linear or oval appearance, with a smooth or verrucous texture, generally alopecic and with very variable color. Moreover, nevus sebaceous is one of the components of the so-called linear nevus syndrome or Schimmelpenning-Feuerstein-Mims syndrome, which is associated with multisystemic complications. The treatment of the lesions is still controversial; however, most experts indicate surgical excision as the most frequently adopted treatment method, in addition to multidisciplinary follow-up when the diagnosis of Schimmelpenning-Feuerstein-Mims syndrome is established. Conclusion: The linear nevus syndrome constitutes a rare manifestation; however, its diagnosis should be considered in children born with nevus sebaceous. There is no consensus yet on the best therapy, but surgical removal has shown to be a viable option.

Chedíak-Higashi Syndrome (CHS) is a rare autosomal recessive disorder caused by mutations in the Lysosomal Trafficking Regulator (LYST) gene, leading to defective lysosomal function in immune cells, melanocytes, and neurons. Clinically, CHS is characterized by a spectrum of symptoms, including immunodeficiency, partial oculocutaneous albinism, bleeding tendencies, neurodevelopmental deficits and progressive neurodegenerative symptoms. The severity of CHS correlates with the type of LYST mutation: the classic form, linked to nonsense or frameshift mutations, presents early in childhood with severe immune dysfunction, recurrent infections, and a high risk of hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory state. Without timely treatment, including hematopoietic stem cell transplantation (HSCT), prognosis is poor, with high mortality in early life. Atypical forms, associated with missense mutations, manifest later with milder immunologic symptoms but inevitably progress to neurological impairment, including cognitive decline and motor dysfunction. Diagnosing CHS is complex due to its rarity, phenotypic variability, and overlap with other disorders. A thorough approach, incorporating clinical evaluation, peripheral blood smear for giant granules in leukocytes, and genetic testing for LYST mutations, is crucial for accurate diagnosis. Management of CHS requires a multidisciplinary approach, focusing on HSCT for immunologic and hematologic stabilization and symptomatic and supportive care for neurological symptoms. Even those patients who undergo stabilizing HSCT eventually develop neurological difficulties. This review provides an in-depth exploration of CHS, covering its epidemiology, clinical presentation, molecular genetics, diagnostic challenges, and current management strategies, while emphasizing the necessity of a comprehensive, multidisciplinary approach to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex (TSC) is a rare neurocutaneous disorder of mTOR pathway dysregulation resulting from pathogenic variants in the TSC1 or TSC2 genes. Expression of this disorder may involve abnormal tissue growth and dysfunction within the brain, kidneys, heart, lungs, eyes, skin, bones, and teeth. Neurological manifestations can include subependymal giant cell astrocytomas (SEGAs), high rates of infantile spasms, drug-resistant epilepsy, developmental delay, cognitive impairment, autism spectrum disorder, and other neurobehavioral manifestations. Here we review the potential clinical manifestations of TSC by system, recommended diagnostic and surveillance testing, genetic testing, currently available therapeutic options, and considerations for education and social support resources given the unique challenges of this multi-system disorder. [ABSTRACT FROM AUTHOR]

First described in the late 1800′s, Sturge-Weber syndrome is one of the more common neurocutaneous disorders. In most cases, it is caused by a somatic mosaic variant in the GNAQ gene driving aberrant overgrowth in endothelial cells which leads to capillary-venous malformations. Characteristic findings are unilateral facial port-wine stain, ipsilateral parieto-occipital leptomeningeal angioma with calcifications and atrophy, and ipsilateral glaucoma, though there is significant variability. The predilection for facial skin and brain is likely due to common embryologic progenitors. The risk of brain involvement is increased with a hemifacial, forehead, or medial facial port-wine stain. Neurologic features include epilepsy, stroke-like episodes, transient or permanent hemiparesis and visual field deficit, headaches, and cognitive and behavioral impairment. Magnetic resonance imaging reveals contrast-enhancing leptomeningeal angiomatosis, progressive atrophy, calcifications, and ipsilateral dilated choroid plexus. The treatment of glaucoma typically requires surgery and port-wine stains are treated with laser therapy. Retrospective data from small cohorts show potential benefits of presymptomatic treatment with anti-seizure medications and/or low dose aspirin. Epilepsy surgery can benefit those with a greater degree of hemiparesis and intractable seizures. Low-dose aspirin has proven effective in lowering the frequency and severity of recoverable stroke-like events. Sirolimus has been reported preliminarily to have satisfactory results regarding cognitive function in pediatric patients, but is not a mainstay of treatment to date. Quality of life is often negatively affected by port-wine stain appearance, intractable seizures, headaches, and mood disorders. Future studies are warranted assessing medication and surgery outcomes, quality of life measures, and timing of imaging and treatment initiation. [ABSTRACT FROM AUTHOR]

A detailed understanding of genetics is critical to the diagnosis, management, and prognostication of neurocutaneous disorders. Inheritance patterns can provide a key to the identification of different neurocutaneous disorders. Autosomal dominant disorders, like neurofibromatosis type 1 and tuberous sclerosis complex, affect males and females equally and are typically seen in every generation of a pedigree due to pathogenic changes to one copy of a gene on a somatic chromosome. Autosomal recessive disorders, such as ataxia-telangiectasia, affect males and females equally but typically skip generations on pedigrees as there needs to be a pathogenic variant of the gene on each of the pair of somatic chromosomes. X-linked disorders such as incontinentia pigmenti and Fabry disease primarily affect males or affect them more severely, but in the case of incontinentia pigmenti, the condition is lethal in males and only females are noted to be affected. The pathogenic variant that is disease causing is on the X sex chromosome, of which females have two and males have one. Somatic mosaic disorders like Sturge Weber syndrome are due to pathogenic variants only in a subset of cells post-fertilization and are not present in gametes, and so are not passed on to the next generation. Conditions that are a result of germline mosaicism are usually identified as autosomal dominant conditions that have not been present in the family prior to a single child being affected, with suspicion strengthening if siblings are diagnosed with the same condition. Regardless of the suspected inheritance pattern, it is essential to consider the ethical implications of genetic testing, including family planning, discovery of consanguinity, disclosure to other potentially affected family members, and diagnostic uncertainty. [ABSTRACT FROM AUTHOR]

Abstract Background A congenital melanocytic naevus (CMN) is a rare skin condition that can be associated with abnormalities of the central nervous system (CNS). These anomalies can sometimes cause severe complications, and rarely death. Adequate information about aetiology and management is therefore crucial. To identify how to monitor patients with CMN, we aimed to estimate the prevalence of neurological involvement in patients with CMN and to summarize what specific neurological signs and symptoms and MRI abnormalities are reported in the medical literature. In addition, we summarized and evaluated the recommendations regarding MRI-screening reported in the medical literature. Methods This review was registered in PROSPERO and reported according to the MOOSE checklist. A search was conducted in EMBASE (Ovid), PubMed, and the Cochrane Library. We included studies with 10 or more patients with CMN, reporting on neurological signs and symptoms or CNS MRI. Study selection, data extraction and methodological quality assessment were performed by two independent reviewers. A meta-analysis was used to assess the prevalence of neurological signs and symptoms. Results Out of 1287 studies, fourteen studies were eligible for inclusion of which eight were included in the meta-analysis. Neurological signs and symptoms prevalence was 7.04% (CI 95% 4.47–10.93%) in the meta-analysis group and 6.26% (95% CI 3.85–10%) in a subgroup of patients with a CMN > 6 cm, evaluated in seven studies. Neurodevelopmental delay and seizures were the most frequently reported signs and symptoms. CNS melanocytosis and hydrocephalus were the most frequently reported MRI abnormalities. It was not possible to estimate the increased risk of neurological involvement in patients with CMN due to low quality of evidence and clinical heterogeneity. Conclusion Standardization in CMN studies and a multi-centre prospective study are needed to evaluate neurological involvement. Based on current literature, it is not possible to make strong recommendations on routine MRI-screening. For now, every clinical centre should decide on its own policy and weigh the advantages and disadvantages of routine MRI.

Background: A congenital melanocytic naevus (CMN) is a rare skin condition that can be associated with abnormalities of the central nervous system (CNS). These anomalies can sometimes cause severe complications, and rarely death. Adequate information about aetiology and management is therefore crucial. To identify how to monitor patients with CMN, we aimed to estimate the prevalence of neurological involvement in patients with CMN and to summarize what specific neurological signs and symptoms and MRI abnormalities are reported in the medical literature. In addition, we summarized and evaluated the recommendations regarding MRI-screening reported in the medical literature.Methods: This review was registered in PROSPERO and reported according to the MOOSE checklist. A search was conducted in EMBASE (Ovid), PubMed, and the Cochrane Library. We included studies with 10 or more patients with CMN, reporting on neurological signs and symptoms or CNS MRI. Study selection, data extraction and methodological quality assessment were performed by two independent reviewers. A meta-analysis was used to assess the prevalence of neurological signs and symptoms.Results: Out of 1287 studies, fourteen studies were eligible for inclusion of which eight were included in the meta-analysis. Neurological signs and symptoms prevalence was 7.04% (CI 95% 4.47-10.93%) in the meta-analysis group and 6.26% (95% CI 3.85-10%) in a subgroup of patients with a CMN > 6 cm, evaluated in seven studies. Neurodevelopmental delay and seizures were the most frequently reported signs and symptoms. CNS melanocytosis and hydrocephalus were the most frequently reported MRI abnormalities. It was not possible to estimate the increased risk of neurological involvement in patients with CMN due to low quality of evidence and clinical heterogeneity.Conclusion: Standardization in CMN studies and a multi-centre prospective study are needed to evaluate neurological involvement. Based on current literature, it is not possible to make strong recommendations on routine MRI-screening. For now, every clinical centre should decide on its own policy and weigh the advantages and disadvantages of routine MRI. [ABSTRACT FROM AUTHOR]

Phakomatoses or Neurocutaneous syndromes are a heterogeneous group of disorders and have variable inheritance pattern. Currently, more than 30 entities are included in this group. These disorders primarily affect the central nervous system; however, skin, viscera, and other connective tissues can also be involved with variable clinical presentation. We will describe and illustrate the various radiological findings of the common entities through the iconography of the cases presented to our department.

Encephalotrigeminal Angiomatosis, also known as Sturge Weber Syndrome (SWS), Dimitri disease, Sturge Kalischer Weber Syndrome is specifically non familial, congenital rare disorder consisting of hamartomatous malformations that may affect eye, skin, and CNS. Failure of proper vascular development is believed to be the most likely cause of the condition. The malformed blood vessels may lead to port wine stains, epilepsy, and glaucoma depending on its location. We are presenting here a triad of case reports on Sturge Weber Syndrome representing individuals belonging to varied age groups.

Scalp dysesthesia (SD), a variant of cutaneous dysesthesia syndrome is an underrecognized cause of scalp pruritus. It usually presents with itch, pain, burning, or stinging sensation over localized or diffuse area of the scalp without any objective findings. Trichoscopy, a rapid and in-office procedure, could aid in the early clinical diagnosis of this condition and initiate management. We report a case of SD in an elderly male diagnosed with the aid of trichoscope, evaluated and treated successfully. [ABSTRACT FROM AUTHOR]

Radiological imaging plays a vital role in clinically diagnosing TSC. TSC prognosis is largely determined by the severity and the extent of the systems affected by it. TSC patients are symptomatically managed, since no cure is present. Healthcare professionals must frequently check-up TSC patients who have a lifelong disorder. [ABSTRACT FROM AUTHOR]

Abstract Radiological imaging plays a vital role in clinically diagnosing TSC. TSC prognosis is largely determined by the severity and the extent of the systems affected by it. TSC patients are symptomatically managed, since no cure is present. Healthcare professionals must frequently check‐up TSC patients who have a lifelong disorder.

Hereditary coproporphyria (HCP) and variegate porphyria (VP) are referred to as neurocutaneous porphyrias (NCP). Data concerning their systemic presentation are limited and no direct attempt of comparison of the two has ever been made. Our aim was to describe the type and frequency of systemic manifestations of NCPs in Israeli patients. A cross-sectional survey was conducted. The study population included all patients with NCP diagnosed at the Israeli National Service for Biochemical Diagnoses of Porphyrias (INSP) between 1988 and 2019. Of the 83 patients with NCP who were alive in 2019, 61 (73%) completed the survey, 40 with VP and 21 with HCP. Systemic symptoms were reported by 63% of the VP group and 62% of the HCP group (p = .96); corresponding rates of cutaneous symptoms were 58% and 5% (p

Neurocutaneous melanosis (NCM; MIM # 249400; ORPHA: 2481], first reported by the Bohemian pathologist Rokitansky in 1861, and now more precisely defined as neurocutaneous melanocytosis, is a rare, congenital syndrome characterised by the association of (1) congenital melanocytic nevi (CMN) of the skin with overlying hypertrichosis, presenting as (a) large (LCMN) or giant and/or multiple (MCMN) melanocytic lesions (or both; sometimes associated with smaller "satellite" nevi) or (b) as proliferative melanocytic nodules; and (2) melanocytosis (with infiltration) of the brain parenchyma and/or leptomeninges. CMN of the skin and leptomeningeal/nervous system infiltration are usually benign, more rarely may progress to melanoma or non-malignant melanosis of the brain. Approximately 12% of individuals with LCMN will develop NCM: wide extension and/or dorsal axial distribution of LCMN increases the risk of NCM. The CMN are recognised at birth and are distributed over the skin according to 6 or more patterns (6B patterns) in line with the archetypical patterns of distribution of mosaic skin disorders. Neurological manifestations can appear acutely in infancy, or more frequently later in childhood or adult life, and include signs/symptoms of intracranial hypertension, seizures/epilepsy, cranial nerve palsies, motor/sensory deficits, cognitive/behavioural abnormalities, sleep cycle anomalies, and eventually neurological deterioration. NMC patients may be symptomatic or asymptomatic, with or without evidence of the typical nervous system changes at MRI. Associated brain and spinal cord malformations include the Dandy-Walker malformation (DWM) complex, hemimegalencephaly, cortical dysplasia, arachnoid cysts, Chiari I and II malformations, syringomyelia, meningoceles, occult spinal dysraphism, and CNS lipoma/lipomatosis. There is no systemic involvement, or only rarely. Pathogenically, single postzygotic mutations in the NRAS (neuroblastoma RAS viral oncogene homologue; MIM # 164790; at 1p13.2) proto-oncogene explain the occurrence of single/multiple CMNs and melanocytic and non-melanocytic nervous system lesions in NCM: these disrupt the RAS/ERK/mTOR/PI3K/akt pathways. Diagnostic/surveillance work-ups require physical examination, ophthalmoscopy, brain/spinal cord magnetic resonance imaging (MRI) and angiography (MRA), positron emission tomography (PET), and video-EEG and IQ testing. Treatment strategies include laser therapy, chemical peeling, dermabrasion, and surgical removal/grafting for CMNs and shunt surgery and surgical removal/chemo/radiotherapy for CNS lesions. Biologically targeted therapies tailored (a) BRAF/MEK in NCM mice (MEK162) and GCMN (trametinib); (b) PI3K/mTOR (omipalisib/GSK2126458) in NMC cells; (c) RAS/MEK (vemurafenib and trametinib) in LCMNs cells; or created experimental NMC cells (YP-MEL). [ABSTRACT FROM AUTHOR]

Objective: Parry-Romberg syndrome (PRS) and en coup de sabre (ECDS) are subtypes of craniofacial localized scleroderma. Systematic analyses of central nervous system imaging findings and their clinical associations in children are lacking. Here, we aim to characterize neuroimaging findings and associated neurological symptoms in these conditions. Methods: Neuroimaging and neurological symptoms of children evaluated at our institution with a diagnosis of PRS or ECDS were retrospectively reviewed. Laterality, location, stability, and number of lesion(s) were evaluated, as was the presence of susceptibility lesion(s) and contrast enhancement. History of seizures or headaches was noted. Results: From 2003 to 2019, 80 patients with PRS or ECDS were followed at our institution. Neuroimaging was completed in 73 and found to be abnormal in 25. In 12 (48%) of these 25 cases, headaches and/or seizures were present. In the vast majority of these cases (22/25, 88%), lesions were ipsilateral to skin findings. White matter was involved in 19 (76%) patients. MRI abnormalities preceded a rheumatological diagnosis in 7 (28%). Susceptibility lesions were noted in 11 (44%), and 8 (73%) of these patients endorsed a history of headaches. Most lesions were in the supratentorial compartment, did not enhance, and were stable at 1-year follow up imaging. Of those with progression, susceptibility findings were present at baseline. Conclusions: Neuroimaging findings in pediatric PRS and ECDS are often supratentorial, stable, unilateral, and ipsilateral to skin findings, and they can precede cutaneous findings. [ABSTRACT FROM AUTHOR]

Background: Segmental neurofibromatosis was initially described by Miller and Sparks (1977) as manifestations of neurofibromatosis limited to a dermatomal, localized distribution. Now termed mosaic neurofibromatosis, previous literature described this disease in children and adolescents with individual case reports and small-numbered case series. This study presents a large series of children and adolescents with mosaic neurofibromatosis. Methods: A retrospective chart review of a single institution medical record database was performed on all cases of mosaic neurofibromatosis diagnosed between the years 1998 and 2017. Eligible subjects were determined by 2 criteria: (1) segmental or unilateral expression of one of more signs of NF I according to those outlined in the NIH criteria and (2) were under 18 years of age at the time of diagnosis. Select information extracted include location of clinical features, NF manifestations (neurofibromas, plexiform neurofibromas, café-au-lait spots, freckling, Lisch nodules), presence of a diffuse area of cutaneous hyperpigmentation, and other significant medical conditions. Results: Sixty-eight cases met established criteria. Average age at diagnosis was 8.28 ± 4.47 years. Thirty-seven (54%) were male and 31 (46%) were female. Localization of the dermatologic manifestations is as follows: left side in 28 (41%) cases, right side in 32 (47%) cases, and bilateral in 8 (11%) cases. Café-au-lait lesions appeared in 64 (94%) of cases and 14 (21%) had axillary and inguinal freckling. Conclusions: This study expands our understanding of the disease characteristics seen in children and adolescents with mosaic neurofibromatosis and confirms the need to focus on pigmentary changes in children with mosaic neurofibromatosis. [ABSTRACT FROM AUTHOR]

Given the complexity of neurocutaneous syndromes, a multidisciplinary approach has been advocated in order to provide optimum care. Subjects and Methods: Retrospective analysis of a cohort of 157 patients during a 3-year period, seen at a newly developed neurocutaneous clinic in a pediatric tertiary care hospital in Athens (Greece); and systematic chart review of the patients diagnosed with neurofibromatosis type 1 during this time period. Results: The most frequent neurocutaneous syndromes were neurofibromatosis type 1 (NF1) in 89 patients and tuberous sclerosis complex in 17. In 20.38% of patients a neurocutaneous syndrome was not confirmed. Approximately 2/3 of the NF1 patients underwent genetic analysis, and for 76.67% of them, a pathogenic mutation on the NF1 gene was revealed. Eighty-one patients manifested with generalized NF1 and eight with mosaic NF1. Dermatological manifestations included café-au-lait macules in all patients, followed by axillary and/or inguinal freckling (n = 57), external plexiform neurofibromas (n = 17), and cutaneous and subcutaneous neurofibromas (n = 11). Approximately half of patients had learning disabilities and attention deficit hyperactivity disorder, followed by mental retardation (n = 9), autistic spectrum disorders (n = 4), headaches (n = 3) and seizures (n = 2). Neuroimaging showed characteristic areas of hyperintensity on T2-weighted images in 74.07% of patients and optic pathway glioma in 19.75%. Two patients developed malignant peripheral sheath nerve tumor. Conclusions: Neurocutaneous syndromes are clinically heterogeneous and the surveillance of potential clinical complications is challenging. The availability of genetic diagnosis and novel imaging methods in this group of disorders is likely to further expand their clinical spectrum. Guidelines for assessment and management will need to be modified based on new available data. [ABSTRACT FROM AUTHOR]

Purpose: To report a rare case of encephalocraniocutaneous lipomatosis (ECCL) presented with characteristic multiple organ involvement. Methods: A 7-day-old white Iranian girl was referred with ocular, skin and brain abnormalities. Results: The findings of nevus psiloliparus, eyelid choristoma and intracranial lipoma were consistent with ECCL. Conclusion: Since the skin and ocular manifestations can be easily observed at birth examination, pediatricians and ophthalmologists should be aware of this condition.

Our skin and nervous system are tightly connected. Numerous dermatomes on our skin provide sensory information to the brain. Because skin changes can occasionally be the first sign of a neurological problem, understanding skin alterations is crucial as it can indicate early about the underlying condition, which can affect the prognosis of the disease. In these cases, the dermatologists' and neurologists' skills are complementary to each other. In this article, we have categorized diseases with neuro-cutaneous manifestations under different headings, such as infections, metabolic diseases, connective tissue disorders, genodermatoses, nutritional deficiency, and the diagnostic criteria of some commonly encountered diseases. Through tabulation, it has been observed that this categorization can serve as a useful reference for managing day-to-day patients who are either diagnosed with the diseases mentioned above or suspected to have the conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Lahoti et al.)

Background: Fibrous cephalic plaques (FCPs) stereotypically develop on the forehead of patients with tuberous sclerosis complex (TSC). They constitute a major feature for TSC diagnosis and may present before other TSC-related cutaneous hamartomas.Objective: To describe the clinical characteristics of FCPs in TSC.Methods: A total of 113 patients with TSC were enrolled in an observational cohort study. Retrospective analysis of medical records and skin photography was performed. FCPs were categorized by anatomic location and size.Results: FCPs were observed in 36% of patients (41 of 113). Of 62 total lesions, 58% were 1 to less than 5 cm, 13% were 5 cm or larger, and 29% were of unknown size mostly because of prior excision. The distribution of lesions was 39% on the forehead, 27% on the face (nonforehead), 3% on the neck, and 31% on the scalp. Fourteen patients had similar lesions less than 1 cm in diameter. Histopathologically, FCPs displayed dermal collagenosis, decreased elastic fibers, and features of angiofibromas or fibrofolliculomas.Limitations: Men were under-represented because the cohort was enriched for patients with TSC with lymphangioleiomyomatosis, which occurs in adult women.Conclusion: Two-fifths of FCPs presented on the forehead, with most of the remainder in other locations on the face and scalp. Better recognition of these lesions may lead to earlier diagnosis of TSC. [ABSTRACT FROM AUTHOR]

Hypomelanosis of Ito is a neurocutaneous disorder characterized by hypopigmented whorls, streaks and patches distributed along the lines of Blaschko, often associated with neurological and musculoskeletal abnormalities. We herein report two patients belonging to ethnic Kashmiri origin with this disorder

Encephalocraniocutaneous lipomatosis (ECCL), also known as Haberland syndrome, is a rare syndrome with unknown etiology. The syndrome is characterized by a triad of unique cutaneous, ocular, and central nervous system (CNS) manifestations. The cutaneous hallmark, nevus psiloliparus (NP), along with overlying alopecia is a constant feature. Choristoma of the eyelid is the most common ocular manifestation, while intracranial lipoma is the predominant CNS finding. Genetic counseling is required to emphasize that the disorder, although congenital, is not inheritable. We present a 21-year-old female with cutaneous, ocular, and CNS features satisfying the diagnostic criteria for ECCL. To our knowledge, this is the first case of ECCL having a large temporal exostosis. The objective of this article is to better understand the phenotypic spectrum of this syndrome whose molecular basis is still unknown.

La hipomelanosis de ito, es un síndrome neurocutáneo con un grado de despigmentación dérmica variable y alteraciones del neurodesarrollo. Se realiza el examen físico-genético a un niño de dos años de edad, observando manchas hipocrómicas, así como otras dismorfias en la cara y el cráneo que se asocian con esta enfermedad, cuyo riesgo de recurrencia es bajo. Después de revisada la literatura médica se confirmó el diagnóstico de la afección para ofrecer adecuado asesoramiento genético a familias con personas afectadas.Hypomelanosis of Ito is a Neurocutaneous Syndrome with a variable degree of dermal depigmentation and neurological disorders. A physical-genetic examination was performed to a two-year old boy presenting hypochromic stains, dysmorphias in face and skull associated with this condition which recurrence risk is low. After revising the medical literature the diagnosis was confirmed to offer the necessary genetic advice to families with patients suffering from this syndrome.

Background: Neurocutaneous syndromes (NCS) are a group of genetic disorders that produce a variety of developmental abnormalities of the skin along with an increased risk of neurological complications. Cutaneous manifestations usually appear early in life and progress with time, but neurological features generally present at a later age. There is a paucity of data regarding the evolution of skin lesions and their correlation with the central nervous system involvement in children. Aim: The primary objective was to track the course of skin lesions in various forms of NCS in the pediatric age group. Our secondary aim was to assess whether there was any predictive value of the lesions in relation to the neurological manifestations. Materials and Methods: This prospective longitudinal study was conducted at a tertiary care pediatric dermatology referral clinic of the Institute of Child Health, Kolkata, West Bengal. Children between the age group 0 and 12 years were included in the study on the basis of standard diagnostic criteria for different NCS, during the period from March, 2000 to February, 2004, and each of the enrolled cases were followed up for a duration of six years. Results: The study population comprised of 67 children (35 boys, 32 girls).The mean age of presentation was 33.8±27.8 months (range 10 days to 111 months). The various forms of NCS observed was neurofibromatosis 1(NF1) (n=33), tuberous sclerosis complex (TSC) (n=23), Sturge Weber syndrome (n=6), ataxia telangiectasia (n=2), PHACE syndrome (n=1), incontinentia pigmenti (n=1), and hypomelanosis of Ito (n=1). The presentations were varied, ranging from predominantly cutaneous to primarily neurological, depending on the disease entity and age group concerned. There was a significant increase in the number of café au lait macules (CALMs) with time (P=0.0002) in NF1, unlike that of hypopigmented macules of TSC (P=0.15). Statistically, no relation was documented between the evolution of skin lesions and neurological manifestations in the major groups. Conclusion: As NCS is not an uncommon disease in children, it is always necessary to find out the subtle neurological signs, whenever we observe any case with cutaneous markers suggestive of NCS. In addition, it is a must to do a detailed dermatological examination in a child with central nervous system involvement, in the pediatric population. However, the neurological course cannot be predicted from skin lesions.

Background: Merkel cell carcinoma (MCC) is a relatively rare and aggressive cutaneous neuroendocrine malignancy characterized by high incidence of local recurrence, distant metastases, regional nodal metastases, and high mortality. Clinically, MCC presents as a persistent asymptomatic red/pink shaped nodule, usually smaller than 2 cm with nontender intracutaneous swelling, with rapidly growing localized disease with lymph node metastases preceding distant metastases. Because of its rare nature and the lack of comprehensive understanding of the disease, management of MCC has been controversial. Methods: An 87-year-old retired Caucasian male with a history of tobacco use, chronic sun exposure, and multiple squamous and basal cell carcinomas presented with a 1.8 × 1.3 cm red, nontender nodule on the dorsum of the proximal phalanx of the left long finger first noticed 6 months prior to presentation. Biopsy was consistent with MCC after which he was treated with wide local excision, full-thickness skin grafting, and sentinel lymphadenectomy (1/4 nodes positive) followed by adjuvant radiation therapy. Results: He recovered appropriately and was clinically and radiographically disease free at 2.5-year follow-up. Conclusion: Although it remains rare, MCC has increased in incidence over the last several decades and has a predilection to occur over sun exposed areas. Highly aggressive, it has a high incidence of regional and distant metastasis as well as local recurrence. As a result, it is important that practitioners involved in the care of skin and hand lesions be aware of this condition and the need for a multidisciplinary treatment approach. [ABSTRACT FROM AUTHOR]

Copyright of International Medical Review on Down Syndrome is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Dysesthesia is a generic term for a cutaneous symptom--such as pruritus, burning, tingling, stinging, anesthesia, hypoesthesia, tickling, crawling, cold sensation, or even pain--without a primary cutaneous condition in a well-defined location that is often caused by nerve trauma, impingement, or irritation. There are multiple types of dysesthesias depending on the body location and the nerves involved. While location, exact symptoms, and etiologies might vary, the underlying theme is that these conditions are of neurologic origin and have dermatologic consequences. For many of these conditions, the symptoms are localized to the skin, and patients frequently present to the dermatologist; it is important for dermatologists to be knowledgeable about these symptoms and their underlying causes. In part II of this continuing medical education review, the primary diagnoses associated with underlying cutaneous dysesthesias will be explored, including scalp dysesthesia, trigeminal trophic syndrome, meralgia paresthetica, notalgia paresthetica, and brachioradial pruritus. The typical demographics in terms of symptoms, location, and patient populations will be discussed in addition to the specific etiologies, workups, and possible treatment options. [ABSTRACT FROM AUTHOR]

Epidermal nevus syndrome is a rare congenital disorder, characterized by epidermal nevi and multiple organ involvement. Multicystic kidney disease has been very rarely reported in this syndrome. Here is the report of a boy presented with multiple epidermal nevi, cardiac anomaly, seizure attack, hemi hypertrophy, and multicystic dysplastic kidney complicated with Wilms' tumor. According to this association, it is suggested to search for dysplastic kidney disease in patients with neurocutaneous disorders.

Neurofibromatosis, though not discussed in depth, is not at all a clinical rarity. The condition has been reported in all races and does not exhibit specific clinical manifestations and features for the occurrence. The hereditary nature has been recognized for long though the depth of mutations is still a long way in short of understanding. It has got a chance occurrence of 50% mutation rate. It occurs with a frequency of one case in approximately 3000 births. Malignant transformation has been reported in a few cases, which underlines the importance of in-depth analysis of this condition. In the present world of molecular studies, pathogenesis of this condition should be discussed and evaluated to decrease the mortality rates and the aim of our case discussion is mainly to highlight the importance of this condition, which needs immediate focus for further enhancements in treatment protocols. [ABSTRACT FROM AUTHOR]

We review the neurospinal and craniofacial imaging findings in vascular neurocutaneous disorders. The patients presented with cutaneous and cerebral lesions associated with craniofacial abnormalities or spinal lesions. Vascular neurocutaneous disorders may involve segmental or localized lesions associated with either low- or high-flow vascular malformations. Other neuroimaging findings include vascular occlusive changes with ischemic stroke, ectatic arteries, aneurysm, cortical migrational disorders such as hemimegalencephaly and congenital anomalies of the posterior fossa. Craniofacial vascular malformations, eye abnormalities, facial deformity and spinal lesions have been reported in some cases. Hamartomatous formation and malignancy have also been reported in some cases. Correlation of clinical findings with neurospinal and craniofacial abnormalities is important to reach a specific diagnosis of some vascular neurocutaneous disorders. [ABSTRACT FROM AUTHOR]

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder of non-malignant tumor growths throughout major organ systems and neurological, neuropsychiatric, renal, and pulmonary co-morbidities. Skin manifestations are readily visible, often develop early in life, and are major features that contribute to TSC diagnosis. Medical photographs of such manifestations are commonly shown as examples from White individuals creating a potential barrier to accurately identifying these features in darker skinned individuals., Objectives: The aim of this report is to raise awareness of dermatological manifestations associated with TSC, compare their appearance by race, and consider how recognition of these features could impact diagnosis and treatment of TSC., Design and Methods: We conducted a retrospective chart review at the TSC Center of Excellence (TSCOE) at the Kennedy Krieger Institute, which included all patients in the center from 2009 (inception) through the end of the calendar year 2015 and analyzed data from the TSC Alliance Natural History Database (NHD)., Results: Among TSCOE patients, 50% of Black patients were diagnosed before the age of 1 year, compared with 70% of White patients. NHD data corroborated this trend showing a significant difference with only 38% of Blacks as compared with 50% of Whites were diagnosed at age ⩽1 year. A significant difference was observed where White participants had higher odds of having received genetic testing in both data sets. While no differences in the total number of TSC features was observed in either data set, shagreen patches and cephalic fibrous plaques were more frequently recorded in the NHD for Black individuals., Conclusion: We highlight a disparity in the representation of Black participants within the NHD, TSCOE, and TSC trials, in addition to differences in utilization of molecular testing and topical mechanistic target of rapamycin (mTOR) inhibitor therapy between Black and White individuals. We show a trend toward later diagnosis age in Black individuals. These differences between races warrant further study across additional clinical sites and other minority groups., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AJP and GVR are employees of the TSC Alliance, a non-profit organization, which reports revenue from individual donors and corporations including BridgeBio, Chemistry Rx, DiRx, Jazz Pharmaceuticals, LivaNova, Marinus, MassMutual, Neurelis, Nobelpharma America, Noema, Ovid, TotalCare Rx, UCB, and Upsher-Smith. The views expressed in this article are those of the authors and do not necessarily reflect the opinion of the TSC Alliance. TTG served as a principal site investigator for a Novartis study (EXIST-3); funding was provided to her institution only., (© The Author(s), 2022.)

Encephalocraniocutaneous lipomatosis (ECCL), also known as Haberland syndrome, is a rare syndrome with unknown etiology. The syndrome is characterized by a triad of unique cutaneous, ocular, and central nervous system (CNS) manifestations. The cutaneous hallmark, nevus psiloliparus (NP), along with overlying alopecia is a constant feature. Choristoma of the eyelid is the most common ocular manifestation, while intracranial lipoma is the predominant CNS finding. Genetic counseling is required to emphasize that the disorder, although congenital, is not inheritable. We present a 21-year-old female with cutaneous, ocular, and CNS features satisfying the diagnostic criteria for ECCL. To our knowledge, this is the first case of ECCL having a large temporal exostosis. The objective of this article is to better understand the phenotypic spectrum of this syndrome whose molecular basis is still unknown. [ABSTRACT FROM AUTHOR]

Sturge.Weber syndrome (SWS), also known as encephalotrigeminal angiomatosis, is a rare vascular neurocutaneous alteration. It is characterized by facial nevus . usually unilateral, seizures, hemiparesis, intracranial calcification, mental retardation and ocular involvement. Nevertheless each case of SWS is unique and exhibits the characteristic features to a varying degree. We report here a case of SWS who presented with features suggestive of this syndrome, and having bilateral facial nevus as well. [ABSTRACT FROM AUTHOR]

Sturge-Weber syndrome has been found to result in hypothalamic-pituitary dysfunction including central hypothyroidism. Because central hypothyroidism is more prevalent in Sturge-Weber syndrome than in the general population, we routinely evaluated thyroid function. Here we describe 5 children with Sturge-Weber syndrome on anticonvulsants and diagnosed with hypothyroidism based on thyroid function testing. All 5 patients were eventually tested utilizing the more accurate free thyroxine equilibrium dialysis assay. Results indicated that only 2 of the 5 patients, who exhibited the most severe symptoms, had true hypothyroidism. This case series demonstrates the benefits of using the free thyroxine by equilibrium dialysis when testing Sturge-Weber syndrome patients on antiepileptic medications. This testing algorithm is more cost-effective and also improves the quality of care by providing an accurate diagnosis more quickly. In addition, we propose consideration of this testing method in any patient taking anticonvulsants, most notably oxcarbazepine. [ABSTRACT FROM AUTHOR]

Abstract: The reconstruction of soft tissue defects in the distal areas of the lower extremity remains a challenge. The distally based sural neurocutaneous flap based on the sural nerve and the superficial sural artery has been used for skin defect reconstruction of the distal third of the leg, the hindfoot, ankle, and heel. We describe our experience and evaluate the reliability of this surgical technique. From 2004-2010, 25 patients with an average age of 32.5 (6 to 70) years were treated using the distally based sural flap for reconstruction of skin defects of the lower third of the leg, the heel, the ankle, and the hindfoot. The skin defect was secondary to trauma in 20 patients (80%) and compromised tendon or bone in all cases. One venous congestion and 2 partial flap necroses were observed. The mean follow-up was 25 (9 to 46) months. The plastic result was assessed as satisfactory in all patients. The donor site morbidity was minimal. The sural flap is a good way to reconstruct soft tissue defects of the lower extremity; this surgical technique provides an alternative to microsurgical reconstruction. [Copyright &y& Elsevier]

Background: Neurocutaneous syndromes (NCS) are a group of genetic disorders that produce a variety of developmental abnormalities of the skin along with an increased risk of neurological complications. Cutaneous manifestations usually appear early in life and progress with time, but neurological features generally present at a later age. There is a paucity of data regarding the evolution of skin lesions and their correlation with the central nervous system involvement in children. Aim: The primary objective was to track the course of skin lesions in various forms of NCS in the pediatric age group. Our secondary aim was to assess whether there was any predictive value of the lesions in relation to the neurological manifestations. Materials and Methods: This prospective longitudinal study was conducted at a tertiary care pediatric dermatology referral clinic of the Institute of Child Health, Kolkata, West Bengal. Children between the age group 0 and 12 years were included in the study on the basis of standard diagnostic criteria for different NCS, during the period from March, 2000 to February, 2004, and each of the enrolled cases were followed up for a duration of six years. Results: The study population comprised of 67 children (35 boys, 32 girls).The mean age of presentation was 33.8±27.8 months (range 10 days to 111 months). The various forms of NCS observed was neurofibromatosis 1(NF1) (n=33), tuberous sclerosis complex (TSC) (n=23), Sturge Weber syndrome (n=6), ataxia telangiectasia (n=2), PHACE syndrome (n=1), incontinentia pigmenti (n=1), and hypomelanosis of Ito (n=1). The presentations were varied, ranging from predominantly cutaneous to primarily neurological, depending on the disease entity and age group concerned. There was a significant increase in the number of café au lait macules (CALMs) with time (P=0.0002) in NF1, unlike that of hypopigmented macules of TSC (P=0.15). Statistically, no relation was documented between the evolution of skin lesions and neurological manifestations in the major groups. Conclusion: As NCS is not an uncommon disease in children, it is always necessary to find out the subtle neurological signs, whenever we observe any case with cutaneous markers suggestive of NCS. In addition, it is a must to do a detailed dermatological examination in a child with central nervous system involvement, in the pediatric population. However, the neurological course cannot be predicted from skin lesions. [ABSTRACT FROM AUTHOR]

There are several rare syndromes combining wrinkled, redundant skin and neurological abnormalities. Although phenotypic overlap between conditions has suggested that some might be allelic to one another, the aetiology for many of them remains unknown. A consanguineous New Zealand Maori family has been characterised that segregates an autosomal recessive connective tissue disorder (joint dislocations, lax skin) associated with neurological abnormalities (severe global developmental delay, choreoathetosis) without metabolic abnormalities in four affected children. A genome-screen performed under a hypothesis of homozygosity by descent for an ancestral mutation, identified a locus at 10q23 (Z=3.63). One gene within the candidate interval, ALDH18A1, encoding Δ1-pyrroline-5-carboxylate synthase (P5CS), was considered a plausible disease gene since a missense mutation had previously been shown to cause progressive neurodegeneration, cataracts, skin laxity, joint dislocations and metabolic derangement in a consanguineous Algerian family. A missense mutation, 2350C>T, was identified in ALDH18A1, which predicts the substitution H784Y. H784 is invariant across all phyla and lies within a previously unrecognised, conserved C-terminal motif in P5CS. In an in vivo assay of flux through this metabolic pathway using dermal fibroblasts obtained from an affected individual, proline and ornithine biosynthetic activity of P5CS was not affected by the H784Y substitution. These data suggest that P5CS may possess additional uncharacterised functions that affect connective tissue and central nervous system function.European Journal of Human Genetics (2008) 16, 1176–1186; doi:10.1038/ejhg.2008.91; published online 14 May 2008 [ABSTRACT FROM AUTHOR]

The phakomatoses of particular interest to neurologists including Sturge-Weber syndrome, neurofibromatosis type 1, neurofibromatosis type 2, Bannayan-Riley-Ruvalcaba syndrome, and Proteus syndrome are presented. The physical manifestations required for clinical diagnosis, the neurologic features, and recommendations for management are given. The molecular etiology and genetic aspects of these disorders are briefly discussed as well as future implications of on-going research. [Copyright &y& Elsevier]

Abstract: Background: Klippel-Trenaunay-Weber syndrome is a rare mesodermal phakomatosis characterized by cutaneous hemangiomata, venous varicosities, and osseous–soft tissue hypertrophy of the affected limb. As the pathologic aspect of KTWS arises from the site in which malformations occur, the clinical picture varies widely from patients who complain for cosmetic reasons to patients with life-threatening lesions. Case Description: We describe a very rare case in which KTWS was associated with a cervical intramedullary cavernous angioma surgically treated. Conclusion: This report confirms the wide range of expression of vascular abnormalities in neurocutaneous developmental diseases and the need of a careful multisystemic evaluation of these patients. [Copyright &y& Elsevier]