Au Lait Spots Research Articles

Primary pilocytic astrocytoma of the cerebellopontine angle in pediatric patient with neurofibromatosis type 1: a case report

BackgroundCerebellopontine angle tumor (CPA) in pediatrics is rare as compared to adults. We describe a case of pediatric pilocytic astrocytoma presented as a right CPA mass with a concurrent clinical diagnosis of neurofibromatosis type 1 (NF1).Case presentationA 14-year-old boy with a newly diagnosed hypertension presented with a short history of headache and blurring vision. Neurological examination revealed bilateral papilloedema, partial right third nerve palsy and mild sensorineuronal hearing deficits. Skin examination identified multiple café au lait spots with cutaneous neurofibromas. Preoperative neuroimaging suggested the diagnosis of an extraaxial CPA mass consistent with meningioma, with obstructive hydrocephalus. A left ventriculoperitoneal shunt was inserted and the child was subjected for a suboccipital retrosigmoid approach for tumor resection. The histopathological features, however, were typical for pilocytic astrocytoma.ConclusionsA careful evaluation of the clinical presentation and radiological images of CPA lesions is necessary prior to surgical embarkment. To the best of our knowledge, this case is the first report of pilocytic astrocytoma in the CPA in pediatric with NF1.

COVID-19 pregnant woman with widespread neurofibromatosis and suprasellar craniopharyngioma presenting for in labour: A challenging scenario

A 29 year old G3P2L2 presented at term in active labour and was tested to be COVID-19 positive. On examination she had multiple papules all over the limbs /abdomen; groin freckles and café au lait spots on the abdomen/lower limbs. She was evaluated for these lesions for the first time in this pregnancy at 20 weeks gestation and MRI brain had shown supra-sellarcraniopharyngioma. She didn’t return for ophthalmology/neurology opinion due to pandemic restrictions. So how does one deliver this patient?. Can vaginal delivery be allowed in the scenario of craniopharyngioma and the possibility of raised intracranial pressure during Valsalva?.

Solitary congenital neurofibroma with overlying melanocytic hyperplasia.

The common embryonic origin of neuroid and melanocytic cells justifies the simultaneous presence of the two cell types in the same neoformation (3). Neurofibroma (NF) can be solitary, diffuse when it has a large extension, and plexiform when it appears as a collection of multiple nodules and cordoniform structures. 10% of diffuse NFs and almost all plexiform NFs are associated with neurofibromatosis (1, 2). Then there is the so-called pigmented or melanotic NF, in which a part of the cells making up the neoplasm is loaded with melanin; this finding is present exclusively in syndromic NF, ie associated with neurofibromatosis. Thus, screening for neurofibromatosis is warranted in the case of plexiform, diffuse, multi-element and melanotic NF (4). In 28% of syndromic NFs and in 4.6% of sporadic NFs there is also a proliferation of epidermal melanocytes, most often in the form of lentiginous melanocytic hyperplasia, but exceptionally in the form of junctional nevus (4). Before assuming that melanocytic hyperplasia is related to NF, it must be considered that melanocytic hyperplasia is also found in cafe au lait spots and therefore we could face a cafe au lait spot superimposed on the NF; this hypothesis should be discarded since lentiginous hyperplasia is also found in sporadic NF and because in any case the histological finding does not always correspond to a clinically evident hyperpigmentation. A casual collision between two different pathologies could also be hypothesized, but this hypothesis is discarded because the limits of melanocytic hyperplasia coincide perfectly with those of the underlying NF (4).

Mandibular neurofibroma with osseous deformities in a 3-year-old child with neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a rare autosomal dominant genetic disorder. It is a multisystem neurocutaneous condition represented by multiple benign tumors of the nerves and skin known as neurofibromas and cafe' au lait spots. However, neurofibroma localized in the mandible is rare. We present a case of a 3-year-old, Egyptian girl with NF1. The girl presented with right mandibular swelling of undetermined duration and multiple hyperpigmented spots on the skin. This case report shows the important role of dentists, as demonstrated in the present case, in the diagnosis and management of this disease, since the diagnosis was made during dental consultation and subsequently managed by the team.

CONSTITUTIONAL MISSMATCH DEFECT REPAIR DISORDER (CMMRD) IN PEDIATRIC HIGH GRADE GLIOMA

Pediatric high grade gliomas(HGG) have dismal prognosis with median survival of 9-15 months after standard radio-chemptherapy. Recent molecular investigations revealed a missmatch repair defect called Constitutional Mismatch Repair Deficiency (CMMRD), which induce pediatric HGG. In CMMRD, there are mutations at least one of the mismatch repair(MMR) genes in both tumoral and non-tumoral DNA. Patients generally have cafe au lait spots resembling the ones in NF-1. Forty-four pediatric high-grade glioma cases operated in our clinic between 2015-2021 were included in the study. PMS2, MLH1, MSH6, MSH2 immunohistochemical antibodies were applied to the sections prepared from paraffin blocks with tumors of these 44 cases. Next generation Sequencing (NGS) Custom Panel for Brain Tumors was performed with DNA and RNA obtained from neoplastic tissue of 2 cases and germline NGS analysis was performed with DNA obtained from peripheral blood in 1 case. MMR protein expression loss was detected in 11 (25%) cases. In 5 (45%) of these 11 cases, MMR protein loss was detected in both neoplastic and non-neoplastic tissue, and these cases were considered as CMMRD. NGS performed in 2 of these 5 cases revealed a hypermutant profile. At least one MMR protein loss was found only in the neoplastic tissue in 6 (55%) of 11 cases, and PMS2 deficiency was the most common. In 1 of these 6 cases, MSH6 deficiency was shown as germline by NGS. CMMRD and MMRD, are disorders with close relationship with pediatric high grade gliomas. Since CMMRD cases also may have cafe au lait spots, they should not be misdiagnosed as NF 1. Temozolomide induce more aggressive tumors in CMMRD ve MMRD, therefore its use is not suggested in those cases. Preliminary literature data advocate use of immunotherapy instead. All pediatric HGG cases should be evaluated for CMMRD and MMRD with molecular investigations to understand their biology.

Prevention of pathological fracture in fibrous dysplasia of proximal femur in a 24-year-old female a rare presentation - a case report

<p class="abstract">Fibrous dysplasia (FD) was historically mentioned in the medical literature in 1938 by Dr. Lichtenstein and in 1942 by Dr. Lichtenstein and Jaffe. The term Jaffe-Lichtenstein syndrome is sometimes used synonymously with monostotic FD or to denote cases of polyostotic FD with café au lait spots, but no endocrine dysfunction. Our case is a 24-year-old female, housewife presented to our hospital with a complaints of right hip pain and backache with difficulty in walking of 6 months duration. She had dull aching pain which increased in intensity with the course of time, there was no radiation, but was aggravated by movements. She was managed with dynamic hip screw along with curettage of the lesion and bone graft, after 9 months of follow up, she had no pain over her hip and there was calcification over the previous lesion, our patient had a very favourable outcome.</p>

Siblings Seckel's syndrome 1 caused by ATR gene variants in a sibpair

Two brothes with Seckel's syndrome 1(SCKL1) were reported and a literature review was carried to provide clinical and genetic information of this rare disease. Clinical data of the two children were collected, and the peripheral blood was extracted for whole exome sequencing. Literature of the disease were reviewed. The two patients were 11 years and 9.5 years old when examined for short stature. They presented with intrauterine growth retardation, intellectual disability, microcephaly, birdhead-like face and coffee au lait spots. The bone age was more than 2 years behind the chronical age and the growth hormone levels were normal. Whole exome sequencing revealed novel compound heterozygous variants c.1A>G (p.M1?) and c.4853-18A>G of ART gene in both children. Children with prenatal onset short stature, developmental delay, microcephaly and special facial featuresshould be considered for the possibility of Seckel's syndrome, whole exome sequencing could help to confirm the clinical diagnosis.

NEUROFIBROMATOSIS-ASSOCIATED LUNG DISEASE: A CASE REPORT

TOPIC: Genetic and Developmental Disorders TYPE: Fellow Case Reports INTRODUCTION: Neurofibromatosis type I (NF-1) is a rare disorder that affects multiple organs, with cutaneous findings being the most well-known. It is an autosomal dominant disease caused by dysplasia of ectoderm and mesoderm with variable expression[1]. NF is characterized by a collection of neurofibromas, café au lait spots, and Lisch nodules. Neurofibromatosis is a rare disease and only 10-20% of the cases have associated diffuse lung disease (NF-DLD). Thus, many of the specific characteristics have yet to be elucidated[2]. CASE PRESENTATION: A 50-year-old white man with NF-1 diagnosed by skin biopsy 2 years ago was seen by his PCP due to worsening shortness of breath associated with a productive cough. Levofloxacin was ordered, but 5 days later symptoms persisted so he was referred to the ED.He reported a prior tube thoracostomy after spontaneous right-sided pneumothorax.Family history was remarkable for neurofibromatosis in his mother and spontaneous pneumothorax in his brother. However, his brother does not have any of the cutaneous findings consistent with NF.He is a former smoker with a 20 pack-year history, quitting a month before admission. He works in a furniture company with exposure to wood dust and chemical fumes for more than 30 years.He denies any fever, chills, chest pain, or weight change. Denies any sick contacts.Physical examination demonstrated no respiratory distress. He had mild bibasilar crackles and multiple neurofibromas throughout his body, more so on his back. SARS-CoV-2, influenza A, influenza B, RSV PCR were all negative. Chest x-ray demonstrated peripheral interstitial opacities. He was started on empiric antibiotic coverage for community-acquired pneumonia. Chest CT showed evidence of upper lobe predominant cystic disease and pulmonary reticular abnormalities in the lower lobes consistent with neurofibromatosis associated diffuse lung disease. Centrilobular emphysema and mild bronchiectatic changes were also noted. He was started on bronchodilators with a 5-day course of prednisone. Respiratory status returned to baseline and he was discharged with a LABA+LAMA inhaler and follow-up with the pulmonary clinic. DISCUSSION: The exact prevalence of NF-DLD is unknown. Based on the limited case reports, NF-DLD is more predominant in men, occurring during the third or fourth decade of life with dyspnea being the more common presenting symptom. Whether smoking plays a role in NF-DLD is still unknown. The typical HRCT finding in NF-DLD is upper-lobe cystic and bullous disease with basilar interstitial lung disease. HRCT results demonstrate bibasilar reticular opacities 50%, bullae 50%, ground-glass opacities 37%, cysts, and emphysema 25%[3]. CONCLUSIONS: NF-DLD is considered one of the rare etiologies of cystic lung disease characterized by upper lobe cystic and bullous disease and lower lobe interstitial changes. REFERENCE #1: V. M. Riccardi, "Von Recklinghausen Neurofibromatosis," https://doi.org/10.1056/NEJM198112313052704, Jan. 19, 2010. https://www.nejm.org/doi/pdf/10.1056/NEJM198112313052704 REFERENCE #2: J. H. Ryu, J. G. Parambil, P. S. McGrann, and G. L. Aughenbaugh, "Lack of Evidence for an Association Between Neurofibromatosis and Pulmonary Fibrosis," Chest, vol. 128, no. 4, pp. 2381–2386, Oct. 2005, doi: 10.1378/chest.128.4.2381. REFERENCE #3: A. C. Zamora, H. R. Collard, P. J. Wolters, W. R. Webb, and T. E. King, "Neurofibromatosis-associated lung disease: a case series and literature review," European Respiratory Journal, vol. 29, no. 1, pp. 210–214, Jan. 2007, doi: 10.1183/09031936.06.00044006. DISCLOSURES: No relevant relationships by Susanti Ie, source=Web Response No relevant relationships by seyed pourshahid, source=Web Response No relevant relationships by Seyedmohammad Pourshahid, source=Web Response No relevant relationships by Edmundo Rubio, source=Web Response

Congenital Pigmentary Anomalies in the Newborn

Congenital pigmentary anomalies may be evident at birth or soon after, with some birthmarks becoming apparent later in infancy or early childhood. It is important to recognize various pigmentary anomalies in the neonate, most of which are benign but a subset of which are associated with cutaneous morbidity or systemic ramifications and require further evaluation. This review will focus on pigmentary mosaicism, congenital melanocytic nevi, nevus spilus, dermal melanocytosis, and pigmentary anomalies associated with neurofibromatosis type 1 (café au lait spots, freckling, plexiform neurofibromas, nevus anemicus), tuberous sclerosis (hypomelanotic macules), and incontinentia pigmenti.

Seizure in Patient with Neurofibromatosis and Amygdala Low-Grade Glioma

A 31-year-old male with history of bipolar disorder, suicidal attempts requiring inpatient hospitalization, and seizures on antiepileptic medications presented with increasing seizure frequency. He was neurologically intact yet had multiple facial, axillary, and inguinal flat pigmented macules (cafe au lait spots) and ophthalmologic examination with iris hamartomas (Lisch nodules) consistent with neurofibromatosis type1. Electroencephalogram was notable for multiple right temporal lobe seizures with anterior temporal interictal epileptiform discharges. Magnetic resonance imaging revealed a T2 hyperintense mass centered in the right amygdala, contiguous with the cystic area. Preoperative intracarotid sodium amobarbital testing showed left-sided language and memory dominance. The patient was operated on for right amygdalohippocampectomy, and initial pathology was consistent with a low-grade neuroepithelial neoplastic process. Further pathologic examination found hypercellular proliferation of predominantly bland, spindled cells with scattered, embedded neurocytic elements with dysplastic appearance, consistent with low-grade glioma. The patient was clinically diagnosed with neurofibromatosis type1.

Misdiagnosis of capillary malformations in darker skin phototypes.

In the dermatologic medical literature, there is an underrepresentation of conditions in individuals of color. Due to the lack of representation, it may be harder for clinicians to recognize certain diagnoses in patients with darker skin phototypes leading to misdiagnosis and affecting overall patient management, outcomes, and satisfaction. Here, we present four Black or Indigenous People of Color who were initially referred for hyperpigmentation, hemihyperplasia, or café au lait spots and found to have syndromic capillary malformations.

English

A 28-year-old female patient presented at ENT OPD with complaints of a slowly growing mass over nasal tip since last 5 years. There were no complaints of pain, nasal obstruction, or epistaxis. There were no skin changes or ulceration over the swelling and sensation was preserved. There was no history of similar kind of swelling in other parts of the body. History of trauma or any form of surgical intervention were excluded. Family history was insignificant. The swelling did not respond to any medications. The patient attended for cosmetic reason solely. Clinical examination showed a soft non-tender 4 cm by 4 cm mass over nasal tip and supratip area. Mobility of the mass was restricted and fixed to the alar cartilages. There was no evidence of café au lait spots or any other skin lesions. Anterior rhinoscopy was unremarkable. Diagnostic nasal endoscopy was also performed but no abnormality was detected. CT scan showed non-specific infiltrative subcutaneous lesions. T1W MRI showed an ill-defined hypodense mass over the nasal tip which was abutting the alar cartilages which showed mild enhancement with contrast (figure 1). T2W MRI showed hyperintense and or hypodense central focus (target sign). FNAC was done and report was suggestive of neurogenic tumour, most probably neurofibroma.

Q-Switched 1064/532 nm Laser with Picosecond Pulse to Treat Benign Hyperpigmentations: A Single-Center Retrospective Study

(1) Benign melanoses are a frequent issue in aesthetic dermatology. Solar lentigo, ephelides, café au lait spots, and other melanoses represent a cosmetic issue for a growing number of subjects. The Q-switched 1064/532-nanometer (nm) laser may be considered the gold standard for management of these aesthetic issues. A new generation of Q-switched lasers, capable of concentrating the energy pulse in the spectrum of hundreds of picoseconds, is emerging, promising better results than previous ones. In this paper, we report the use of a Q-switched laser with a picosecond pulse to manage hypermelanoses. (2) Methods: 36 patients seeking melanosis removal were retrospectively enrolled at Magna Graecia University of Catanzaro. Treatment parameters, although variable, were the following: 1064 nm with a pulse duration of 450 picoseconds (ps) for dermic lesions and 532 nm with 370 ps for epidermal lesions. Up to four treatments, with a minimum interval between laser treatments of 30 days, were performed. After the last session, patients’ satisfaction was assessed at a three-month follow up with a Visual Analogue Scale (VAS). Two blinded dermatologists measured the aesthetic outcome using a five-point scale comparing pictures before laser sessions and during follow-up. (3) Results: 36 patients were enrolled; 23 were females (63.9%) and 13 males (36.1%). The mean reported age was 49.2 ± 18.9 years. All participants were assessed with a complete/almost complete melanosis removal at the dermatological evaluation, with a mean VAS score of 9.39 ± 0.90. (4) Conclusions: The Q-switched 1064/532 nm laser may be considered the main weapon in treating benign hypermelanosis. The picosecond pulse seems to guarantee better results than other devices. However, a clinical trial comparing Q-switched nanosecond pulse with picosecond pulse is necessary to confirm this study’s findings.

Clinical and radiological features of orbito-temporal neurofibromatosis

Neurofibromatosis- 1 (NF- 1) is an autosomal dominant condition belonging to the well-known group of neurocutaneous syndromes. It affects 1 in 3500 persons. It is caused by a mutation in the neurofibromin gene localized to chromosome 17q11.2. which codes for a protein involved in the normal cell cycle regulation. Therefore NF-1 gene mutations predispose the individual to various benign and malignant tumors. The diagnosis of NF-1 remains largely clinical, given its characteristic lesions. Here we describe one such case with hallmark lesions of NF-1. A 12-year-old boy presented with a slow-growing and progressive right upper lid mass causing severe drooping, vision impairment and facial disfiguration. On detailed ophthalmic examination he was found to have severe ptosis, Lisch nodules and keratoconus. A systemic examination revealed café au lait spots and axillary freckling. Radiological imaging showed sphenoid wing dysplasia, encephalocele and optic pathway glioma. The patient was taken up for debulking surgery and a referral to the neurosurgery department was sent. He has been on follow up for last 12 months. This case first presented to an ophthalmology clinic and thus, as an ophthalmologist, keeping in mind the associated intraorbital and intracranial pathology can be life-saving. A multidisciplinary approach is needed in the management of such severe cases of NF-1.

Neurofibromatosis Type 1 in Children: A Single-Center Experience.

Objective:Neurofibromatosis (NF) is the most common autosomal dominantly inherited neurocutaneous syndrome. The characteristic features of NF type 1 (NF-1) are café au lait spots, axillary and inguinal freckling, peripheral neurofibromas, optic pathway glioma, and Lisch nodules. The present study aimed to analyze the clinical features of children with NF-1.Materials and Methods:In this study, the children with NF-1 diagnosed and followed-up in our center between 2000 and 2020 were retrospectively evaluated. Demographic and clinical features of patients were defined.Results:The study group consisted of 52 patients. Of those, 25 were boys and 27 were girls. The children’s median age at diagnosis was 5.9 years (1-15.8). Café au lait (CAL) spots and axillary/inguinal freckling were observed in 50 and 24 patients, respectively. Neurofibroma was present in 22 cases. Ten of the cohort had optic gliomas, and 39 of them had cranial hamartomas. Orthopedic complications such as scoliosis, tibial pseudoarthrosis, and osteoporosis were observed in 13 patients. Eleven children had neurocognitive disorders.Conclusions:Early diagnosis is important in neurofibromatosis to prevent the complications of the disease. Also, neurological development and secondary malignancy follow-up should be done carefully in this group of patients.

RARE-16. A PATIENT WITH MOSAIC POST-ZYGOTIC KRAS-G12D PATHOGENIC VARIANT PRESENTING WITH A SYMPTOMATIC SPINAL NEUROFIBROMA AND LARGE SEGMENTAL TRUNCAL CAFÉ AU LAIT SPOT

An 11 year old boy presented with a three month history of progressive bilateral lower extremity weakness associated with recent intermittent incontinence. Spine MRI showed a right-sided T11-T12 paraspinal mass extending through the neural foramina into the epidural space and causing severe spinal cord compression. Skin showed a large macular lightly-hyperpigmented café au lait spot with irregular borders along the T10-T12 dermatome extending from the spine to approximately the anterior-axillary line. He was suspected to have segmental neurofibromatosis type 1 (NF1) as no additional clinical findings, radiographic features or family history of NF1 were identified. Patient underwent T10-12 laminectomy for resection of the epidural tumor component. Post-operative MRI showed resolution of the mass effect on the thecal sac and cord, with expected tumor residual lateral to the neural foramen. His residual spinal tumor and mild scoliosis remained stable over the two years of follow up to date. Pathological and molecular analysis of the resected tumor revealed a neurofibroma harboring an activating KRAS c.35G>A, p.Gly12Asp (KRAS-G12D) pathogenic variant at 27% variant allele frequency. Melanocytes cultured from two hyperpigmented skin biopsies showed the same KRAS-G12D pathogenic variant. This KRAS-G12D pathogenic variant was not found in leukocytes, indicating a post-zygotic origin. No NF1 pathogenic variant was identified in tumor tissue, melanocytes or leukocytes. The clinical findings were consistent with a mosaic KRASopathy due to a post zygotic KRAS-G12D pathogenic variant. The presence of the KRAS variant in the spinal neurofibroma and overlaying café au lait spot without an NF1 etiology in associated tissues demonstrates overlapping variability of presentations of RAS-MAPK pathway disorders. This case highlights the need for full clinical and genetic evaluation of patients presenting with segmental neurocutaneous disorders.

NEUROFIBROMATOSIS TYPE 1 IN MULTIPLE SCLEROSIS IN SAUDI ARABIA: CASE REPORT AND LITERATURE REVIEW

Background: Neurofibromatosis type I(NF1) is a neurocutaneous autosomal dominant disorder that has variable skin and neurological manifestation and Multiple sclerosis (MS) is not among these neurological sequalae of Neurofibromatosis. Only 26 cases have been reported worldwide to have the combination of these two neurological diseases, and none of them from Saudi Arabia.We are presenting a young lady who was diagnosed to have Multiple Sclerosis, Relapsing remitting form as she is fitting the clinical and the radiological criteria, and by the age of 29 years, she was thoroughly investigated for multiple café au lait spot lesions in the trunk and neurofibromas and history of childhood seizures. Case Presentation:29-year-old lady who was diagnosed to have Relapsing- Remitting Multiple Sclerosis (RRMS) 7 years ago as she is fulfilling the clinical and radiological criteria of Multiple sclerosis and maintained on Interferon beta 1a 44 mcg subcutaneous every other day then shifted to Fingolimod. Upon encountering her in the clinic, there were multiple café au lait spot lesions in the trunk and neurofibromas. Genetic testing showed pathogenic nonsense variant c.574C>T p.(Arg192*) in exon 5 of the NF1 gene. Conclusion:Relapsing remitting form of multiple sclerosis (RRMS) can be associated with Neurofibromatosis type 1(NF1), not only progressive form and NF1 can be related to spontaneous mutation in 50% of cases (no family history).

Ruptured tibial artery in neurofibromatosis type 1: A case report.

IntroductionNeurofibromatosis type 1 (NF-1) or von Recklinghausen's disease, an autosomal dominant genetic disorder, is characterized by a café au lait spot and cutaneous neurofibromas. It typically involves the skin, nerves, bones, muscles, and eyes, and occasionally involves vascular complications and can lead to life-threatening hemorrhage.Case presentationWe present the case of a 77-year-old female with a posterior tibial artery rupture with NF-1. She presented with sudden right lower leg swelling, pain, paresthesia, and paralysis; computed tomography images revealed popliteal artery aneurysm with surrounding hematoma, expanding from the posterior aspect of the knee to the calf. Diagnosed with compartment syndrome, due to a ruptured right popliteal artery aneurysm, she underwent prosthetic replacement of the popliteal aneurysm. Intraoperatively, the fragility of the popliteal artery was noted, although no perforation site was recognized despite the aneurysm; active bleeding originated from the hematoma between the calf muscles. Intraoperative digital subtraction angiography revealed an extravasation at the branch of the posterior tibial artery that was managed by coil embolization of the posterior tibial artery.Clinical discussionAlthough the frequency of NF-1 vasculopathy is unknown, vasculopathy is the second most common cause of mortality in patients with NF-1, after malignancy. The less invasive endovascular approach might be preferable for treating NF-1-related aneurysm. The NF-related vasculopathy lesion sites are diverse, and intraoperative angiography would help confirm the diagnosis.ConclusionNF-1-related vasculopathy may be associated with vascular fragility, and the endovascular approach might be preferable. Endovascular-first approach could have helped in correct diagnosis in the present case.

Tuberous sclerosis complex associated neuropsychiatric disorder in children: experience sharing from a tertiary care hospital

Background: Tuberous sclerosis complex (TSC) is a genetic disorder where there is multisystem involvement. Most important manifestations are neurological and psychiatric disorders. These disorders should be detected timely and addressed adequately. The common psychiatric disorders are autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), intellectual disability (ID), learning disorder etc. This study has been done to describe the pattern of psychiatric disorders in children with TSC.Methods: This is an observational study taken place in a tertiary care hospital taken place on Children of 0-18 years of age. The study subjects were 84 patients with TSC. Detail history and physical examination had been done along with neuroimaging, EEG and target organs screening. Different psychometric tool was used for psychiatric evaluation. Results: Total 84 patients were included in this study, mean age was 7+3.96 years, 54% were female. Physical finding were as follows: ash leaf spot, shagreen patch, adenoma sebaceum, cafe au lait spot, rhabdomyoma, renal cyst and angiomyolipoma etc. Seventy patients had epilepsy, most common being focal epilepsy (45.7%), 17.1% had epileptic spasm. Fifty percent patients had developmental delay. Regarding psychiatric disorders, most common disorder was ADHD in 27.38%, ASD in 23.81% and both in 10.71%. ID was found in 20.24% study subjects. Early onset of seizure was associated with more psychiatric disorders.Conclusions: Neuropsychiatric manifestations of TSC are diverse and often are poorly addressed. The most commonly found disorders in this study were ADHD, ASD and ID. Early onset of seizure was associated with the psychiatric disorders in TSC.

Characterization of Two Loss-of-Function NF1 Variants in Chinese Patients and Potential Molecular Interpretations of Phenotypes.

Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by cafe’-au-lait spots, skinfold freckles, the formation of neurofibromas, skeletal dysplasia, vascular dysplasia, and an increased risk of malignant tumors. In this study, two Chinese NF1 children troubled with bone lesions or hypertension were reported. A de novo NF1 mutation (c.4925T > A/p.V1642E) and a maternally inherited NF1 mutation (c.4883T > A/p.L1628∗) were identified by molecular sequence. According to the ACMG/AMP guidelines, the c.4925T > A was classified as variants of uncertain significance (VOUS) while the c.4883T > A mutation was identified as likely Pathogenic. Further study found that these two NF1 mutants had lost their function to inhibit the Ras/Erk signaling and the proliferation of cells, which could interpretate some phenotypes of these two NF1 patients. We also observed these two NF1 mutants displayed decreased protein stability with increased ubiquitination levels compared with that of wild-type NF1.