Linear Nevus Sebaceous Syndrome Research Articles

Calcified Sclero-Choroidal Choristomas in Mosaic RASopathies: A Description of a New Imaging Sign

PurposeTo evaluate the imaging and clinical features of unusual calcified lesions seen in the fundus of mosaic RASopathy patients. DesignSingle-center retrospective observational study. SubjectsTen eyes with calcified fundus lesions in 7 mosaic RASopathy patients. MethodsThe lesions were evaluated with fundus photography, oral fundus fluorescein angiography, B-scan ultrasonography, Magnetic Resonance Imaging (MRI), and Computed Tomography (CT) scan where available. Main Outcome MeasuresThe imaging characteristics of calcified fundus lesions were assessed. ResultsWe found seven patients with mosaic RASopathies, 5 males and 2 females (3 with Linear Sebaceous Nevus Syndrome, 3 with Oculoectodermal Syndrome, and 1 with Encephalocraniocutaneous Lipomatosis) with molecular confirmation in 5 cases, all 5 having KRAS-pathogenic variants. Calcified fundus lesions were identified in 10 eyes (bilateral in 3 patients), appearing as slightly elevated, creamy-yellow lesions around or adjacent to the optic nerve, extending supero-nasally; all but two of these lesions involved both the choroid and sclera, with two of them only involving the sclera at the time of examination. One case developed a choroidal neovascular membrane (CNV) necessitating intravitreal bevacizumab injections. All 7 patients had B-scan ultrasonography and the lesion appeared as a hyperechogenic area with an acoustic shadow posteriorly despite reduced gain. Five patients had MRI, and where fundus lesions were present, there was a focal defect in the sclero-choroidal layer. Four patients had a CT scan and all four showed calcifications affecting both the posteromedial sclero-choroid and adjacent medial rectus muscle. Two of these patients had normal eye movements, one had a unilateral fixed adducted eye and a vestigial fibrous medial rectus muscle seen in imaging and intraoperatively, and the fourth had marked exotropia with a right gaze deficit affecting both eyes. ConclusionsWe propose that the lesions seen in this cohort are calcified sclero-choroidal choristomas (CaSCCs) and should be suspected in mosaic RASopathies when creamy-yellow lesions are seen in the fundus. If identified, the possibility of choroidal neovascularization should be considered during follow-up. In all cases where a CT scan was performed, a novel sign of sclero-muscular calcification involving the medial rectus muscle was seen.

Reversibility and developmental neuropathology of linear nevus sebaceous syndrome caused by dysregulation of the RAS pathway

Linear nevus sebaceous syndrome (LNSS) is a neurocutaneous disorder caused by somatic gain-of-function mutations in KRAS or HRAS. LNSS brains have neurodevelopmental defects, including cerebral defects and epilepsy; however, its pathological mechanism and potentials for treatment are largely unclear. We show that introduction of KRASG12V in the developing mouse cortex results in subcortical nodular heterotopia and enhanced excitability, recapitulating major pathological manifestations of LNSS. Moreover, we show that decreased firing frequency of inhibitory neurons without KRASG12V expression leads to disrupted excitation and inhibition balance. Transcriptional profiling after destabilization domain-mediated clearance of KRASG12V in human neural progenitors and differentiating neurons identifies reversible functional networks underlying LNSS. Neurons expressing KRASG12V show molecular changes associated with delayed neuronal maturation, most of which are restored by KRASG12V clearance. These findings provide insights into the molecular networks underlying the reversibility of some of the neuropathologies observed in LNSS caused by dysregulation of the RAS pathway.

Linear nevus sebaceous syndrome with bilateral ocular involvement in a Bangladeshi child: A case report with literature review

The linear sebaceous nevus is one of a variety of epidermal nevi, which is a congenital ectodermal hamartoma that occurs due to post-zygotic mosaic mutation. Such sebaceous nevus is one of the commonest nevi, and up to 30% are associated with syndromic associations, which are rare. After cutaneous manifestation, central nervous system and ocular anomalies are common and found in almost every case. Multiorgan involvement can lead to various minor or major morbidities. Adequate knowledge and a high degree of suspicion can identify this rare disease and can minimize unwanted morbidity.

Sleep Problems in Children With Neurocutaneous Syndromes: A Cross-Sectional Study.

Introduction: The prevalence and patterns of sleep disturbances in neurocutaneous syndromes are variable and understudied. Methods: Cross-sectional study for 18 months at a tertiary care pediatric hospital, involving 100 children with neurocutaneous syndromes aged between 4 and 10 years using the Children's Sleep Habits Questionnaire-Abbreviated. Results: In 100 children with neurocutaneous syndromes, 47 (47%) had significant sleep problems. In subgroup analysis, 7 of 17 children with neurofibromatosis 1, 24 of 63 children with tuberous sclerosis complex, 10 of 12 children with Sturge-Weber syndrome, 2 of 3 children with linear nevus sebaceous syndrome, and each of the children with hypomelanosis of Ito, McCune-Albright syndrome, megalencephaly-capillary malformation syndrome, and unclassified neurocutaneous syndrome had significant sleep problems. Conclusion: The prevalence of sleep problems in our study population was not more than that observed in the general pediatric population. Prospective multicentric studies are needed to comprehend sleep problems in children with neurocutaneous syndromes.

A case report to assess the safety and efficacy of Burosumab, an investigational antibody to FGF23, in a single pediatric patient with Epidermal Nevus Syndrome and associated hypophosphatemic rickets

Epidermal Nevus Syndrome (ENS), also known as Cutaneous Skeletal Hypophosphatemia Syndrome or Linear Sebaceous Nevus Syndrome, is caused by a mosaic somatic mutation of RAS (Rat Sarcoma genes) which leads to abnormally elevated levels of fibroblast growth factor 23 (FGF23). FGF23 is a major regulator in phosphate homeostasis. There are multiple disorders, along with Epidermal Nevus Syndrome (ENS), that result in unusually high circulating levels of FGF23. This increase ultimately leads to renal phosphate wasting and reduced levels of 1,25-dihydroxy vitamin D. Across these disorders, the clinical symptoms are similar and often include osteomalacia (hypophosphatemic rickets in children), muscle weakness, fatigue, joint deformities, bone pain, and fractures. Burosumab (KRN23), is an IgG1 monoclonal antibody that binds to the FGF23 receptor and inhibits the activity of FGF23. This leads to an increase in serum phosphate levels. Burosumab emerged as a potential therapy in FGF23 overactivity disorders. Burosumab was successful in the treatment of X-linked hypophosphatemia (XLH) and is now FDA-approved for its treatment. Studies have indicated that Burosumab therapy in subjects with XLH consistently increases and sustains serum phosphorus levels and tubular reabsorption of phosphate without a major impact on urine calcium levels or vitamin D metabolism. We studied the effect of Burosumab treatment in a single pediatric patient with Epidermal Nevus Syndrome. Serum phosphorus rose gradually as we titrated the dose of Burosumab upwards. During treatment, a persistent elevation of parathyroid hormone levels was noted along with a persistent elevation of serum calcium. We presumed the patient had tertiary hyperparathyroidism. However, after the removal of three parathyroid glands, the pathology came back with a single enlarged parathyroid adenoma. Subsequently, his calcium and PTH, and phosphorus levels stabilized while taking only Burosumab.ClinicalTrials.gov NCT04320316.

Pathogenesis of FGF23-Related Hypophosphatemic Diseases Including X-linked Hypophosphatemia

Since phosphate is indispensable for skeletal mineralization, chronic hypophosphatemia causes rickets and osteomalacia. Fibroblast growth factor 23 (FGF23), which is mainly produced by osteocytes in bone, functions as the central regulator of phosphate metabolism by increasing the renal excretion of phosphate and suppressing the production of 1,25-dihydroxyvitamin D. The excessive action of FGF23 results in hypophosphatemic diseases, which include a number of genetic disorders such as X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia (TIO). Phosphate-regulating gene homologous to endopeptidase on the X chromosome (PHEX), dentin matrix protein 1 (DMP1), ectonucleotide pyrophosphatase phosphodiesterase-1, and family with sequence similarity 20c, the inactivating variants of which are responsible for FGF23-related hereditary rickets/osteomalacia, are highly expressed in osteocytes, similar to FGF23, suggesting that they are local negative regulators of FGF23. Autosomal dominant hypophosphatemic rickets (ADHR) is caused by cleavage-resistant variants of FGF23, and iron deficiency increases serum levels of FGF23 and the manifestation of symptoms in ADHR. Enhanced FGF receptor (FGFR) signaling in osteocytes is suggested to be involved in the overproduction of FGF23 in XLH and autosomal recessive hypophosphatemic rickets type 1, which are caused by the inactivation of PHEX and DMP1, respectively. TIO is caused by the overproduction of FGF23 by phosphaturic tumors, which are often positive for FGFR. FGF23-related hypophosphatemia may also be associated with McCune-Albright syndrome, linear sebaceous nevus syndrome, and the intravenous administration of iron. This review summarizes current knowledge on the pathogenesis of FGF23-related hypophosphatemic diseases.

Reversibility and Developmental Neuropathology of Linear Nevus Sebaceous Syndrome Caused by Dysregulation of the RAS Pathway

Reversibility and Developmental Neuropathology of Linear Nevus Sebaceous Syndrome Caused by Dysregulation of the RAS Pathway

Ophthalmic Manifestation and Pathological Features in a Cohort of Patients With Linear Nevus Sebaceous Syndrome and Encephalocraniocutaneous Lipomatosis.

Purpose: This study aimed to figure out the association between ophthalmic and pathological features in patients with Linear Nevus Sebaceous Syndrome (LNSS) and in patients with Oculoectodermal Syndrome—Encephalocraniocutaneous Lipomatosis (OES-ECCL).Methods: It is a retrospective, non-consecutive, observational case series. Twenty-seven patients (12 with LNSS and 15 with OES-ECCL, 41 eyes) referred to the Department of Ophthalmology of the Shanghai Ninth People's Hospital between 2000 and 2020 were included. The mean age of the study population for the first-time consult was 5.7 years, ranging from 3 months to 34 years. Clinical notes, pathological records, and imaging findings were reviewed in all the patients.Results: Fourteen (51.9%) cases showed bilateral ocular involvement. Epibulbar choristomas were seen in all the patients. All the lesions involved the conjunctiva and cornea simultaneously. Multiple lesions were observed in 12 eyes. Of the 14 excised lesions, 11 were found to be complex choristomas. Further, 24 (89%) patients had eyelid coloboma. Also, 13 patients (48%) were diagnosed with strabismus, and 12 patients (44%) had abnormal fundus imaging, including optic nerve hypoplasia.Conclusions: LNSS and OES-ECCL shared common ophthalmic features, including epibulbar choristomas with distinctive characteristics, eyelid coloboma, strabismus, and optic nerve hypoplasia. The complex choristoma was found to be associated with the diseases. These specific patterns can be diagnostic clues to distinguish them from other syndromes, such as craniofacial defects, and to remind ophthalmologists that such patients require additional dermatological and neurological examinations and referral. Moreover, a thorough evaluation of ocular conditions is imperative for early interventions.

Identification of KRAS mutation in a patient with linear nevus sebaceous syndrome: a case report

BackgroundLinear nevus sebaceous syndrome (LNSS) is a rare genetic disease characterized by large linear sebaceous nevus typically on the face, scalp, or neck. LNSS could be accompanied by multisystem disorders including the central nervous system. Herein, we report gene mutational profile via whole exome sequencing of both lesional and non-lesional skin samples in a LNSS patient.Case presentationA 17-year-old girl presented with multisystem abnormalities, including large skin lesions, ocular disorders, abnormal bone development and neurological symptoms. A diagnosis of LNSS was established based on clinical manifestations, histopathological and imaging findings. The skin lesions were resected and no recurrence was noted at the time of drafting this report. Whole exome sequencing of genomic DNA revealed the following 3 mutations in the lesions of the index patient: KRAS (c.35G > A, p.G12D), PRKRIR (c.A1674T, p.R558S), and RRP7A (c. C670T, p.R224W), but no mutation was found in the healthy skin and peripheral blood sample of the index patient, or in the blood samples of her parents and sibling. PCR-mediated Sanger sequencing of DNA derived from lesional skin sample of the index patient verified KRAS mutation, but not PRKRIR (c.A1674T, p.R558S) and RRP7A (c. C670T, p.R224W). None of the 3 mutations was found in Sanger sequencing in skin lesions of 60 other cases of nevus sebaceous patients.ConclusionsOur findings show the relevance of KRAS mutation to LNSS, providing new clues in understanding related genetic heterogeneity which could aid genetic counselling for LNSS patients.

Ocular manifestations and surgical treatment of the linear nevus sebaceous syndrome

Objective: To report the clinical and pathological features and surgical treatment of the linear nevus sebaceous syndrome. Methods: It was a retrospective case series study. The clinical records of 11 patients (14 eyes) who were diagnosed as linear nevus sebaceous syndrome between April 2009 and February 2018 at Beijing Tongren Hospital were analyzed. Data collected included sex, age, clinical manifestations, disease site, pathological features, surgical treatment and therapeutic effects. Results: There were six males and five females, aged 6 months to 7 years (mean, 2.8 years). The nevus sebaceous was located at the head (9 patients), face (5 patients) and neck (3 patients). The most common ocular manifestations were blepharocoloboma (13 eyes) and external ocular mass (9 eyes). Surgical treatment was performed in 9 patients (11 eyes), including lid reconstruction in all these eyes, corneal and conjunctival mass resection in four patients (4 eyes), eyelid tumor resection in 5 patients (5 eyes), and symblepharon separation and conjunctival sac reconstruction in 3 patients (5 eyes). Pathological examinations of the external ocular, corneal and conjunctival masses (6 eyes) confirmed the diagnosis of complex choristoma. All operated patients had improved appearance. Conclusions: Linear nevus sebaceous syndrome has characteristic cutaneous lesions and ocular manifestations. Histopathologically, all epibulbar lesions prove to be complex choristomas. The appearance of patients with linear nevus sebaceous syndrome can be significantly improved by oculoplastic surgery. (Chin J Ophthalmol, 2020, 56: 846-852).

SAT-LB085 First Report of Burosumab (Anti-FGF23 Monoclonal Antibody) for Rickets Complicating HRAS-Associated Cutaneous Skeletal Hypophosphatemia Syndrome

Background: Cutaneous skeletal hypophosphatemia syndrome (CSHS) is caused by somatic mosaicism of a RAS family gene (ie. HRAS, NRAS, KRAS). CSHS features: 1) congenital epidermal, melanocytic, or sebaceous nevi, 2) elevated circulating FGF23 levels that cause renal phosphate wasting and skeletal hypomineralization, and 3) focal bone lesions ipsilateral to the nevi as a possible source of excess FGF23. Conventional therapy for rickets in CSHS (phosphate salts and bioactive vitamin D) mirrors treatment for X-linked hypophosphatemia (XLH) with elevated circulating FGF23. Current therapy aims to treat signs and symptoms rather than the etiology. Clinical Case: A 21-month-old boy with left, widespread, unilateral nevus sebaceous developed bilateral lower extremity bowing with a wide-based gait. His serum phosphorus level was low at 2.1 mg/dl (Nl: 3-6) and FGF23 was elevated at 279 RU/mL (Nl: < 230). We prescribed conventional therapy for hypophosphatemic rickets and diagnosed linear sebaceous nevus syndrome, confirmed by mutation analysis of affected skin harboring HRAS p.Q61R (c.182A>G). Adherence to medical therapy was problematic, and he sustained 3 major long-bone fractures. By age 6 years, a walker was required to ambulate short distances with mostly wheelchair-dependence from pain and muscle weakness. Based on his elevated FGF23 level and clinical decline, burosumab (anti-FGF23 fully human monoclonal antibody), FDA-approved in 2018 for XLH, was initiated off-label. After weaning conventional therapy, burosumab was administered subcutaneously as a single dose of 0.8 mg/kg (20 mg) and decreased to 0.3 mg/kg (6 mg) two weeks later. Burosumab was then given every 2 weeks and adjusted by 0.1 mg/kg to maintain fasting serum phosphorus in the low-normal range for age (3.5 - 4.5 mg/dL). Laboratory and clinic follow-up occurred just prior to each injection for 3 months until serum phosphorus was stable as he received approximately 0.4 mg/kg (8 mg per dose). Biochemical testing and clinic visits will occur monthly for 3 months and are planned for quarterly afterwards, with repeat radiological imaging every 3-6 months for the first year of therapy. Duration of burosumab treatment has been 5 months. After his initial burosumab dose, serum phosphorus increased from 1.7 to 3.7 mg/dL and remained normal [Nl: 3.0 - 6.0 mg/dL] thereafter. Radiographs of his wrists and knees 3 months into therapy revealed striking improvement of his rickets but persisting focal bone lesions, characteristic of CSHS, on the left side. He now walks independently with endurance, strength, and resolving pain. Quality-of-life is markedly improved. Burosumab treatment is being tolerated well without side effects. Conclusion: Burosumab seems to be an effective therapy for FGF23-mediated rickets in pediatric CSHS. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Epilepsy in Neurological Phenotypes of Epidermal Nevus Syndrome

Epidermal nevus syndrome (ENS) encompasses a group of congenital genetic disorders characterized by the association of an epidermal nevus with systemic anomalies including the brain. The most frequent subtype with neurological features is <i>linear sebaceous nevus syndrome</i> (LSNS), followed by keratinocytic nevus syndrome (ENS). Both are caused by postzygotic <i>RAS</i> mutations. All forms of ENS are mosaic disorders that share a common embryological basis and pathogenesis as <i>neurocristopathies</i>. The lines of Blaschko indicate the cutaneous migratory pathways of neural crest. Neural crest defects explain the development of nevi and associated multisystemic anomalies: brain, ocular, osseous, muscular, orodental, cardiovascular, endocrine, renal/urinary, and adipose tissue. Epilepsy and cognitive and motor deficits are caused mainly by hemimegalencephaly (HME), a closely related mosaic anomaly caused by somatic mutations in PI3K–AKT3–mTOR pathway that determines overgrowth. The usual onset of epilepsy is in the neonatal period or early infancy, often as infantile spasms. The pioneer description of nevus sebaceous in 1895 by Jadassohn is the basis for delineating the LSNS. The eponym “Schimmelpenning syndrome” as a substitute for that long-established term makes no sense in the context of the large number of authors who contributed to defining this syndrome. A review of 111 cases of LSNS and other subtypes enabled a classification of neurological phenotypes; epilepsy occurred in 77% and HME in 38%. Three distinctive additional syndromes also are within the spectrum of ENS: CLOVES, SCALP, and Heide's syndrome. The impact of epilepsy in patients affected by ENS is related to time of onset and extent of brain anomalies. Timing of the mutation determines the phenotype and severity of the systemic lesions.

Linear nevus sebaceous syndrome with lissencephaly

Linear nevus sebaceous syndrome is a congenital neurocutaneous syndrome comprising of nevus sebaceous, seizures and mental retardation. We report a 6 month old female child with a linear nevus sebaceous over the face and scalp, whose brain imaging revealed ipsilateral lissencephaly with hemimegalencephaly. Lissencephaly is rarely reported in this syndrome.

Hemihypoplasia and venous anomalies associated with linear nevus sebaceous syndrome

Hemihypoplasia and venous anomalies associated with linear nevus sebaceous syndrome

Chapter 2 - Phenotype/genotype correlations in epidermal nevus syndrome as a neurocristopathy

Epidermal nevus syndrome (ENS) is a term that encompasses several phenotypes defined by the association of an epidermal nevus with one or more congenital systemic anomalies, mainly ocular, osseous and cerebral. The two most frequent, keratinocytic nevus syndrome and linear sebaceous nevus syndrome, also correspond to the neurological phenotypes. They both exhibit overlapping and distinctive features but same etiology: post-zygotic mosaic mutations in RAS genes. Their pathogenesis is due to defective neural crest, further confirming that they are the same basic entity contradicting the concept that they are a group of heterogeneous syndromes with different etiologies. Both have been reported for more than a century. The sebaceous nevus, hallmark of linear sebaceous nevus syndrome, was defined by Jadassohn in 1895; the large number of subsequent contributors in defining this syndrome precludes the introduction of eponyms. Three other distinctive phenotypes within the spectrum of ENS with CNS involvement are CLOVES, SCALP and Heide's syndromes. Recognition of neurological phenotypes with multisystemic involvement should invoke multidisciplinary investigation and management. In some ENS phenotypes the association of melanocytic nevi with keratinocytic and sebaceous nevi, all sharing RAS mutations, predicts multisystemic involvement, in particular severe rickets and osseous anomalies. Phenotype is, therefore, the starting point for clinicians to guide genetic, neurological and other systemic investigations for patient management. The most frequent brain malformation in neurological phenotypes of ENS is hemimegalencephaly (HME). Epilepsy is the most frequent neurological symptom, in particular infantile spasms, with or without HME. The impact of neurological and systemic manifestations is related to onset and extent of the mutations. Timing of the mutation determines phenotype and severity. Proteus syndrome is a neurological phenotype of epidermal keratinocytic nevus syndrome not an independent, separate syndrome.

P19.21: Successful laser coagulation for twin‐to‐twin transfusion syndrome and occurrence of linear nevus sebaceous syndrome in one monochorionic twin

<scp>P</scp>19.21: Successful laser coagulation for twin‐to‐twin transfusion syndrome and occurrence of linear nevus sebaceous syndrome in one monochorionic twin

Linear nevus sebaceous syndrome in a neonate conceived by intracytoplasmic sperm injection

Linear nevus sebaceous syndrome is a multisystem disorder including nevus sebaceous, which is the hallmark of this syndrome, together with central nervous system, ocular and skeletal anomalies. We report a case of extensive skin lesions, CNS and eye anomalies in a full term infant who was conceived by intracytoplasmic sperm injection.

Linear nevus sebaceous syndrome with hypophosphatemic rickets with elevated FGF-23

Linear nevus sebaceous syndrome (LNSS) is a rare congenital neuroectodermal disorder characterized by involvement of the skeleton and central nervous system. We report the case of a 5-year-old girl who had LNSS with hypophosphatemic rickets and multiple fractures of her extremities. Biochemical tests revealed a high serum level of fibroblast growth factor-23 (FGF-23) but normal levels of immunoglobulin E (IgE) and parathormone (PTH). FGF-23 mRNA expression in the skin lesions of our patient's skin was found to be below the limit of detection in all samples tested by quantitative-PCR analysis. It is possible that an as-yet unidentified substance increases FGF-23 expression LNS lesions.

Linear Nevus Sebaceous Syndrome in a Patient With Atypical Associated Abnormalities

A 3-year-old girl was diagnosed as having linear nevus sebaceous syndrome. The nevus sebaceous was located on the left side of the face and neck. An unusually large lacrimal gland was completely ectopic below the entire left conjunctiva, with secondary ectropion of the left upper eyelid. The patient had the unusual finding of dentigerous cysts in both maxillary sinuses. Computed tomography scan showed atrophy of the left cerebral hemisphere, accompanied by a history of seizures; furthermore, the patient was mentally retarded. This phenotypic pattern of linear nevus sebaceous syndrome is typical for patients with multiple associated abnormalities.

Elevated FGF-23 and parathormone in linear nevus sebaceous syndrome with resistant rickets

Sirs, Linear nevus sebaceous syndrome (LNSS) is a neuroectodermal disorder, which may be associated with hypophosphatemic rickets in childhood. The pathogenesis of hypophosphatemia is unclear and has been attributed to increased levels of fibroblast growth factor-23 (FGF-23) [1]. We report a patient with LNSS, hypophosphatemic rickets; and high blood levels of FGF-23, immunoglobulin (Ig) E, and parathormone (PTH). A 5-year-old boy, son a non-consanguineous marriage, was referred for increasing skin lesions on face and arms since birth and lower limb deformities. The child was developmentally normal for age. He had clinical and radiological features of rickets and multiple, linear, hyperpigmented plaques following the morphological pattern of Blaschko lines over the right side of his scalp, face, ear, and arms. Investigations showed normal blood levels of creatinine, calcium, and 25-hydroxyvitamin D; low phosphate (1.8–2.0 mg/dl); and raised alkaline phosphatase and parathormone (PTH). There was evidence of phosphate wasting, with low tubular maximum for phosphate reabsorption per glomerular filtration rate (TmP/GFR) (Table 1). Contrast-enhanced computed tomography (CT) of the head was normal. Following a diagnosis of LNSS with hypophosphatemic rickets, he was treated with phosphate supplements at a dose of 750–1,000 mg and alpha calcidiol 0.25 μg every day. The patient reported recently with poor compliance with medications, increasing bony deformities, and enlarging cutaneous nevi. Investigations showed similar blood findings, with low levels of phosphate and TmP/GFR and markedly raised PTH (Table 1). Serum IgE level was 179 IU/ml (normal <60 IU/ml), and FGF-23 was 1,265 pg/ml (normal 10–60 pg/ml). Skeletal survey showed features of osteopenia with rickets and multiple radiolucent cysts over the left third metacarpal, ulna, and femur, as well as bilateral radii. Biopsy of the nevus showed epidermal papillomatous sebaceous gland hyperplasia with clusters of primordial hair follicles, suggesting LNSS. Immunohistochemistry for FGF-23 was negative (courtesy Dr. Fukumoto, University of Tokyo). Ultrasonography of the neck and Tc sestamibi scan for parathyroid glands showed no evidence of adenoma. Whole-body positron emission tomography for tumors was negative. The patient is receiving phosphate supplements (1.5 g/day) and alpha calcidiol (0.5 μg/day); phosphate levels range between 2.6–2.8 mg/dl. This patient with LNSS is interesting because we found hypophosphatemia but markedly high levels of PTH and FGF-23, an association that is rarely reported. Aschinberg et al. reported the association between rickets and LNSS, with improvement of musculoskeletal symptoms and hypophosphatemia after excision of the nevus [3]. Infusion of extract from the nevus resulted in reduced renal tubular reabsorption of phosphate in animals [3]. The putative phosphatonin was FGF-23 based on demonstration of its elevated blood levels in a patient with LNSS [1]. Hoffman et al. also showed that treatment with octreotide and S.K. Sethi was an IPNA Fellow at All India Institute of Medical Sciences, New Delhi. S. K. Sethi : P. Hari :A. Bagga Division of Pediatric Nephrology, All India Institute of Medical Sciences, New Delhi, India