Lait Spots Research Articles

The Role of Magnetic Resonance Imaging in the Diagnosis of Spinal Dumbell Neurofibromatosis: A Case Report from a Specialist Hospital in Port Harcourt

Neurofibromatosis occurring in the spine also known as spinal neurofibromatosis (SNF) is a rare disease entity and they occur either unilaterally or bilaterally at the spinal roots. The low prevalence rate of the disease and scarcity of previous literatures is the main aim for this report.
 Our case study is a 29-years-old lady who presented to the Radiology department for a lumbosacral spine MRI, on account of both lower limb weakness, paresthesia, unsteady gait and finally inability to walk. The symptoms have been there since she was 14 years (15 years of progressive symptoms). She also presented with multiple macules on the skin (café au lait spots). Magnetic Resonance Imaging (MRI) of the lumbosacral spine revealed bilateral spinal neurofibromas at the spinal roots of the fourth lumbar vertebra to the sacral/coccygeal vertebrae with destruction of the sacro-coccygeal bones. MRI of the brain revealed no abnormalities in the brain and optic tract. The patient fulfilled the National Institutes of Health (NIH) criteria and that of revised diagnostic criteria for Neurofibromatosis (NF1).
 The patient also presented with lack of pain which could be due to impairment in sensory neurons. We describe a case of spinal neurofibromatosis diagnosed by MRI in a young lady with progressive lower limb weakness, paresthesia, sensory loss, café-au- lait spots and paraplegia.

A rare case of neurofibromatosis with proptosis-orbital neurofibroma

Neurofibromatosis, an oculo-­?neuro-­?cutaneous syndrome is characterized by multisystem involvement. A 65 years old male patient came to the dept. of ophthalmology, S. V. R. R. Govt. General Hospital, Tirupati with the complaints of protrusion of his left eye, noticed by him 20 days back, with a history of drooping of left upper eyelid. On physical examination, the patient was short statured (Ht: 148cm) with scoliosis, there were multiple neurofibromas on the skin all over the body and face, freckles in the axillary region and cafe-­?au-­?lait spots over his trunk. On ocular examination, the patient had eccentric proptosis of left eye where the eyeball was shifted downwards (Hypotropia of 450) and forwards (24mm on exophthalmometry) with severe ptosis of left upper eyelid with restriction of extraocular movements. No palpable mass was noted. Finger insinuation between the orbital margin and the globe was possible. Right eye was normal. Slitlamp examination showed multiple Lisch nodules on the surface of iris in both eyes. Fundoscopy showed inferior coloboma choroid of left eye with normal fundus picture in Right eye Binocular diplopia was noted on elevating the upper eyelid of left eye. Forced duction test was positive. CT scan showed proptosis of left eye. Ultrasound B-­?scan of left eye showed a well defined mass lesion of 1.5x2cm size, slightly hyperechoic, with minimal vascularity, situated away from the globe, along the lateral aspect of the orbit suggestive of Orbital neurofibroma. The rare entity in the present case is the Localized form of orbital neurofibroma. Diagnosis in the present case is clinical. Linkage analysis using polymorphic DNA markers can be performed, allowing prenatal diagnosis or presymptomatic diagnosis. Keyword: Oculoneurocutaneous syndrome, Orbital neurofibroma, Lisch nodules

FIBROUS DYSPLASIA OF BONES.

Fibrous dysplasia is an ailment , that can include , one or a few bones and is portrayed by bone deformations, pain and fractures, arising due to bone weakening. A few patients can also present with endocrine dysfunction ( precocious puberty) and cutaneous cafe '- au - lait spots.[1] Determination depends on X-ray assessment. Anticipation is to be surveyed with X-rays and markers of bone remodelling. A few newer comprehensions , of the patho - physiology have been made in the past I0 years. It is presently perceived that fibrous dysplasia is brought about , by a physical initiating transformation of the Gs alpha subunits , of the protein G, bringing about an expanded cAMP fixation and in this way, brings about anomalies of osteoblasts separation, and then subsequently these osteoblasts, creates abnormal bone. There is also an expansion in interleukin-6-initiated osteoclastic bone resorption, which forms the basis of reasoning, for treating these patients with bisphosphonates. In the previous 10 years, the bisphosphonate pamidronate has been utilized by imbuement for fibrous dysplasia (two courses for each year), with great outcomes regarding pain and, in about half of patients, the topping off of osteolytic sores.[2]

ANTI-PD-1 Treatment in a Family with Constitutional Mismatch Repair Deficiency Syndrome with Multiple Cancers from Turkey. Is Cancer Immunoprevention with Checkpoint Inhibitors HAS a Role in CASES with Homozygous Mutationis

Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare childhood cancer predisposition syndrome resulting from biallelic germline mutations of MMR genes and it is poorly recognised by clinicians so far. Here we present affected children of 1st degree consanguinous parents diagnosed with CMMRD syndrome due to germline bi-allelic MSH 6 mutations with multiple cancers and mimicking NF 1 in a family from Turkey A 8-yr-old female,referred with brain tumor with follow up Neurofibromatosis 1 and Familial Mediterranean Fever. One of the female siblings had died of aggressive brain tumor at 4yrs of age, one male sibling due to medulloblastoma, followed by diagnosis of a metachronous metastatic colon adenocarcinoma at 15yrs of age. No additional cancers have been reported in the extended family, with the exception of colorectal cancer in the maternal and paternal great uncle diagnosed at age 45 years, paternal grandfather with brain tumor at 70 age of years and maternal aunt with papillary thyroid cancer at age 50 years. Her physical examination was unremarkable other than 8 to 10 cafe-au- lait spots and hipodense macules with irregular borders on her body. Laboratory tests were normal with low IG G2 levels. Cranial MRI revealed a mass in the left cerebellar region, subcortical hyperdens lesions in fronto-parietal area. She underwent near-total resection,histopathology revealed classic desmoplastic medulloblastoma.Postoperative craniospinal MRI showed no residue or metastasis.Craniospinal RT and CT of CCNU, cisplatin,VCR were given. At initial, due to colon adenocarcinoma history in her family, the colonoscopy was performed which did not reveal any polypoid lesions. In addition, because of the family history, the genetic analysis was carried out and disclosed a novel homozygous single base insertion mutation in exon 5 of the MSH 6 gene ( c.3261dupC/ p.Phe1088Leu ).Five cycles of previously mentioned chemotherapy combination and Nivolumab, obtained by pediatric extended use, was commenced at 3 mg/kg/dose in every 2 weeks as new polyps were detected in the following colonoscopy. After 10th dose,9 polyps were removed of tubular adenoma histopathology .She is still on antiPD1 treatment (18.th dose and in remission. Last colonoscopy revealed only one polyp mm in size. The genetic test results of the family: Blood samples were obtained from parents and siblings. One of the siblings was also found to be homozygous. She is 24- months- old age and has multiple cafe-au-lait spots on her body. She is still under follow up with screening tests for development of possible neoplasms. The parents and the other two siblings ( 11 and 6 years old boys) were heterozygous for the mutation. The male sibling who died from medulloblastoma and metastatic colorectal carcinoma genetic test had revealed same homozygous mutation. Conclusions: As the use of immune modulation for cancer prevention rather than therapy has gained considerable attention, we wonder if 24-months-old female sibling with homozygous mutation will be a candidate for cancer immunoprevention with AntiPD1drugs. We think that an international collaboration is required to evaluate guidelines for screening and treatment of malignancies and to explore prevention strategies patients with CMMRD syndrome. Disclosures Beksac: Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau.

Giant Pelvic Neurofibroma in Patient with Plexiform Sciatic Neurofibroma and Neurofibromatosis Type 1

BACKGROUND:Neurofibromatosis is a genetic disease with an autosomal dominant type of inheritance. It is a multisystem disease in which, besides skin manifestations, there is a possibility for the involvement of other organs and systems, and an atypical variant of neurofibromatosis type 1 can also be observed- the so-called plexiform neurofibroma. In patients with this inherited disease, mortality is higher due to the existing risk for malignant transformation and development of malignant peripheral nerve sheath tumours (MPNSTs) or neurofibrosarcoma.CASE REPORT:We present a 25-year-old woman with neurofibromatosis type 1 and a family history of the disease-father and grandmother with NF-1, with fatal outcome in the grandmother as a result of malignant transformation to neurofibrosarcoma. The patient has clinical data for multiple cafés- au- lait spots on the skin of the trunk, upper and lower limbs, and plexiform tumour formation in the seating area. From the performed imaging diagnostic there are available MRT data for 1) giant pelvic neurofibroma, 2) plexiform giant neurofibroma in the subcutaneous fat on the right thigh and gluteal fat tissue to the right, passing through the midline in the area of the external genitalia, leading to deformation of the front wall of the sacrum with bilateral meningoceles and 3) diffuse involvement of the bladder wall from the process in the area of the trigonum vesicae felleae/the two urethral ostium, as well as 4) the presence of neurofibromas in the course of the iliac vessels on the right. Surgical removal of the oval pelvic formation, identified as neurofibroma was planned, as well as the initiation of systemic therapy with Sirolimus for the plexiform sciatic formation, infiltrating the bladder.CONCLUSION:Neurofibromatosis type-1 is a problematic disease due to the parallel systemic involvement of different organs and systems, which can be both limited and diffuse. Limited tumour lesions in the form of neurofibromas with diverse localisation (as in the patient we describe) could be surgically removed without difficulty. On the other hand, the diffuse involvement of internal organs within a giant, network-3spreading plexiform neurofibromas (as in the described patient) makes interdisciplinary interventions impossible, and therefore therapeutic alternatives should be considered.

A case report of neurofibromatosis Type 1 – plexiform variant

Neurofibromatosis type 1 is a neurocutaneous disorder which is autosomal dominant. The incidence is 1 in 2500 births. It was earlier termed Von Recklinghausen’s disease. The clinical features range from café-au lait spots, multiple neurofibromas of the skin along with plexiform variants, axillary freckling, optic glioma and Lisch nodules. This paper reports a case of Neurofibromatosis type 1 with review of literature.

Lower limbs deformities in patients with McCune-Albright syndrome: Tomography and treatment.

The skeletal changes in McCune-Albright disease are usually severe because of the polyostotic form of the disease. Trendelenberg gait and limited mobility are the most common presenting features. The constellation of Café-au lait spots and polyostotic bone involvement is commonly referred to as McCune-Albright's syndrome (MAS). One boy and 4 girls (7-16 years) were sought in our departments from 1998 to 2012. Limb length discrepancy was the main clinical presentation. Repetitive micro-fractures caused the development of 'Shepherd crook' deformity with pain were the main burden. Because of the repetitive micro-fractures and the significant deformity that distorted the integrity of the long bones which were associated with pain. We referred to re-alignment valgus osteotomy with internal fixation to preserve proper alignment. Moreover, guided growth technique with 8-plates was performed in 1 case. Tendency to progressive unilateral lower limb deformity in patients with MAS is usually associated with thinning and expansion of the cortex and distortion of the normal lower limb integrity secondary to repetitive micro-fractures. The latter is a situation which warrants surgical treatment to re-align the deformity and to preserve function. Prophylactic intramedullary nailing via the application of locking nails to ensure stabilisation of the femoral neck was found to be effective. However, nevertheless, the mosaic nature of MAS means any cell, tissue and organ in any site of the body could be affected to varying degrees. The clinical manifestations are a diversity of the disorder ranging from mild clinical signs to severe life-threatening disease.

Association between Neurofibromatosis Type I and Central Giant Cell Lesion: Case Report

Neurofibromatosis type I (NF1), or Von Recklinghausen disease, is characterized by cafe-au-lait spots and neurofibromas of the skin, bone defects, iris hamartomas (Lisch nodules) and tumors in the central nervous system. The central giant cell lesion (CGCL) is a non-neoplastic entity, intra-osseous, radiolucent, uni or multilocular, well-defined edges, and it can change the position of the teeth, but rarely causes resorption of them. The association between CGCL and NF1 has been described in the literature. Patient C.R.P, 42 years old, female, who has NF1 attended the service presenting asymptomatic swelling in the anterior maxilla and discrete painless intraoral bulge in the anterior mandible with approximate evolution of one year. Incisional biopsy was performed, and the result was CGCL. The patient didn’t have hyperparathyroidism. Treatment consisted of curettage of the lesion and bone regularization performed three years ago, without signs of recurrence. The occurrence of CGCL in multiple locations is uncommon and it is usually associated with hyperparathyroidism, cherubism, and can be also found in syndromes such as: Ramon Jaffe Campanacci, Noonan-like and NF1. The patient presented four features of NF1 (multiple skin neurofibromas, cafeau- lait spots, Lisch nodules and freckles in the armpits) and CGCL in two locations, which corroborate the existence of this association in the literature. The apparent relationship between NF1 and an increased incidence of CGCL s in the jaws could represent a coincidental association, genetic relationship, or susceptibility to developing CGCL in abnormal bone quality. In cases of multiple CGCL, the presence of hyperparathyroidism, cherubism and syndromes such as NF1, should be considered. One realizes the importance of investigation of systemic factors and clinical signs for performing differential diagnosis. The differentiation of these lesions in aggressive and nonaggressive should be done to improve individual treatment plan. Surgical curettage is acceptable for the treatment of non-aggressive CGCL.

A CASE OF METACHRONOUS BILATELAL BREAST CANCER ASSOCIATED WITH VON RECKLINGHAUSEN'S DISEASE

A case of bilateral breast cancer associated with von Rechlinghausen's disease is reported. [First cancer: left breast cancer] A 47-year-old woman was admitted to the hospital because of a left breast tumor with a gradual grouth for two years. The left breast tumor was measured 7.0cm in diameter and multiple neurofibromas and cafe'au lait spots were scattered on the entire skin surface. Modified radical mastectomy was performed under the diagnosis of breast cancer. Histologically, the tumor was papillotubular carcinoma without metastasis to the axillary lymph node. [Second cancer: right breast cancer] A right breast tumor 2.5cm in diameter was detected 3 years after the resection of the left breast cancer. Modified radical mastectomy was performed under the diagnosis of breast cancer. Histologically, the tumor was papillotubular carcinoma with intra-ductal component, and no metastasis to the axillary lymph node. was revealed. Clinically and histologically, metachronous bilatelal breast cancer was diagnosed.

Neonatal dermatoses of relevant medical significance: their report in the newborn's file

OBJECTIVE: To check the report of neonatal dermatoses of medical relevance (congenital melanocytic nevus, sebaceous nevus, cafe-au-lait spots, Port-wine stain, ash leaf maculas) in the newborn's file. METHODS: The authors carried out a cross-sectional study in two hospitals in the city of Belo Horizonte. All children born during a consecutive period of 4 months were examined within their 36 first hours of life by a dermatologist who reported all clinically relevant dermatoses (congenital melanocytic nevus, sebaceous nevus, cafeau- lait spots, Port-wine stain, ash leaf macules). Simultaneously, the dermatologist's report was cross checked with the pediatrician's. RESULTS: Neonatal dermatoses of clinical relevance were found in 42 (5.6%) out of 752 children examined during this period. However, the report in the neonate's file could be detected only in 5 (11,9%) out of 42 children. CONCLUSIONS: Clinically relevant dermatoses were underreported in the neonate's file in this study. There is a clear need to stimulate the detection and report of these skin disorders so that parental advice, treatment and genetic counseling can be adequately indicated.

What's new in neurofibromatosis?

The last decade has seen major developments in our knowledge of the different forms of neurofibromatosis. Evidence based clinical diagnostic criteria and management guidelines have been developed. The genes for the two major forms, neurofibromatosis type 1 (Nfl) and type 2 (Nf2), have been cloned. This has provided insight into the pathogenesis of these diseases and long-term hope of some form of treatment being developed. In this article we briefly review these developments and try to answer the questions that paediatricians most often ask 'neurofibromatologists'. The term neurofibromatosis or Von Recklinghausen's disease was previously used to describe all patients with variable combinations of caf6 au lait (CAL) spots and tumours of the peripheral and/or central nervous system. As systematic clinical research began in the 1970s it became clear that within this umbrella term there were several distinct diseases. Differentiation of these is not just an academic exercise (and one which clinical geneticists are fond of!), their natural history and management are quite distinct. The other major development in recent years has been the network of support available to families through the UK Neurofibromatosis Association.

The Russell-Silver's dwarf.

SUMMARYThe Russell‐Silver's dwarf is a symptom complex made up of shortness of stature, small size for gestation age, variation in sexual development, asymmetry, peculiar facies, cafe‐au lait spots, clinodactyly and syndactyly. Pseudohydrocephalus may be a prominent feature. Knowledge of the syndrome will prevent useless pneumoencephalography.