OBJECTIVE: To explore the types of NF1 gene variants and clinical characteristics among patients with Neurofibromatosis type I (NF1). METHODS: Clinical data of 12 patients diagnosed at Ningbo Women and Children's Hospital between December 2019 and May 2022 were retrospectively analyzed. The probands and their family members were subjected to high-throughput sequencing, and candidate variants were verified by Sanger sequencing and chromosome microarray analysis. RESULTS: The 12 patients had ranged from 4 months to 27 years old, with a male-to-female ratio of 2 : 1. Cafè-au-lait spots were found in all patients. 83.3% of them also had axillary and/or inguinal freckling, 58.3% had neurofibromas, and 16.7% had congenital pseudarthrosis of the tibia. Five types of NF1 gene variants were identified in the patients, including 5 nonsense variants, 4 frameshift variants, 1 missense variant, 1 splice variant, 1 large deletion involving the whole gene. Six patients were found to harbor de novo variants, 2 had inherited the variants from their parents, and 4 were not verified for their parental origin. The c.3379del (p.Thr1127Glnfs*15) and c.6628_6629del (p.Glu2210Thrfs*10) variants were unreported in literature and databases. CONCLUSION Most NF1 patients may present with Cafè-au-lait spots initially and are due to pathogenic variant of the NF1 gene. High-throughput sequencing can efficiently identify such variants among the patients and enable the definite diagnosis.
Child ; Humans ; Female ; Male ; Neurofibromatosis 1/diagnosis* ; Cafe-au-Lait Spots/diagnosis* ; Genes, Neurofibromatosis 1 ; Retrospective Studies ; Frameshift Mutation

Objective: To summarize the clinical characteristics of epileptic seizure associated with neurofibromatosis type 1 (NF1). Methods: From January 2017 to July 2023 at Children's Hospital Capital Institute of Pediatrics, medical records of patients with both NF1 and epileptic seizure were reviewed in this case series study. The clinical characteristics, treatment and prognosis were analyzed retrospectively. Results: A total of 15 patients(12 boys and 3 girls) were collected. Café-au-lait macules were observed in all 15 patients. There were 6 patients with neurodevelopmental disorders and the main manifestations were intellectual disability or developmental delay. The age at the first epileptic seizure was 2.5 (1.2, 5.5) years. There were various seizure types, including generalized tonic-clonic seizures in 8 patients, focal motor seizures in 6 patients, epileptic spasm in 4 patients, tonic seizures in 1 patient, absence in 1 patient, generalized myoclonic seizure in 1 patient and focal to bilateral tonic-clonic seizure in 1 patient. Among 14 patients whose brain magnetic resonance imaging results were available, there were abnormal signals in corpus callosum, basal ganglia, thalamus or cerebellum in 6 patients, dilated ventricles of different degrees in 3 patients, blurred gray and white matter boundary in 2 patients, agenesis of corpus callosum in 1 patient and no obvious abnormalities in the other patients. Among 13 epilepsy patients, 8 were seizure-free with 1 or 2 antiseizure medications(ASM), 1 with drug resistant epilepsy was seizure-free after left temporal lobectomy, and the other 4 patients who have received 2 to 9 ASM had persistent seizures. One patient with complex febrile convulsion achieved seizure freedom after oral administration of diazepam on demand. One patient had only 1 unprovoked epileptic seizure and did not have another seizure without taking any ASM. Conclusions: The first epileptic seizure in NF1 patients usually occurs in infancy and early childhood, with the main seizure type of generalized tonic-clonic seizure and focal motor seizure. Some patients have intellectual disability or developmental delay. Most epilepsy patients achieve seizure freedom with ASM.
Male ; Female ; Humans ; Child, Preschool ; Child ; Neurofibromatosis 1/diagnosis* ; Retrospective Studies ; Intellectual Disability ; Electroencephalography ; Epilepsy/etiology* ; Seizures/etiology*

Identification of certain abnormalities of the chest wall can be extremely helpful in correctly diagnosing a number of syndromic conditions and systemic diseases. Additionally, chest wall abnormalities may sometimes constitute diagnoses by themselves. In the present pictorial essay, we review a number of such conditions and provide illustrative cases that were retrospectively identified from our clinical imaging database. These include pentalogy of Cantrell, Klippel-Feil syndrome, cleidocranial dysplasia, Poland syndrome, osteopetrosis, neurofibromatosis type 1, Marfan syndrome, Gardner syndrome, systemic sclerosis, relapsing polychondritis, polymyositis/dermatomyositis, ankylosing spondylitis, hyperparathyroidism, rickets, sickle cell anemia, thalassemia, tuberculosis, septic arthritis of the sternoclavicular joint, elastofibroma dorsi, and sternal dehiscence.
Anemia, Sickle Cell ; Arthritis, Infectious ; Cleidocranial Dysplasia ; Diagnosis ; Gardner Syndrome ; Hyperparathyroidism ; Klippel-Feil Syndrome ; Marfan Syndrome ; Neurofibromatosis 1 ; Osteopetrosis ; Pentalogy of Cantrell ; Poland Syndrome ; Polychondritis, Relapsing ; Retrospective Studies ; Rickets ; Scleroderma, Systemic ; Spondylitis, Ankylosing ; Sternoclavicular Joint ; Thalassemia ; Thoracic Wall ; Tuberculosis

OBJECTIVE: To identify pathogenic mutation for a family with neurofibromatosis type 1(NF1) and provide prenatal diagnosis for them. METHODS: Mutation analysis of the sporadic family with NF1 was performed with target captured next generation sequencing and Sanger sequencing. RNA samples were extracted from the lymphocytes of NF1 patient and her parents. RT-PCR and Sanger sequencing were performed to analyze the relative mRNA expression in the samples. Prenatal diagnosis of the pathogenic mutation was offered to the fetus. RESULTS: A novel splicing mutation c.1260+4A>T in the gene was found in the proband of the family, but was not found in her parents.cDNA sequencing showed that 13 bases inserted into the 3' end of exon 11 in the gene lead to a frameshift mutation. Prenatal diagnosis suggested that the fetus did not carried the mutant. CONCLUSIONS The : c.1260+4A>T mutation found in the NF1 patient is considered to be pathogenic, which provides information for family genetic counseling and prenatal diagnosis.
DNA Mutational Analysis ; Female ; Frameshift Mutation ; Genetic Testing ; Humans ; Male ; Neurofibromatosis 1 ; diagnosis ; genetics ; Pregnancy ; Prenatal Diagnosis

PURPOSE: To report a case of moyamoya syndrome after an additional diagnosis of neurofibromatosis type 1 (NF 1) using an ophthalmic examination in a middle-aged patient with moyamoya disease. CASE SUMMARY: A 60-year-old male with no specific past medical history except moyamoya disease visited our hospital for an ophthalmic examination. Two years prior, he had been diagnosed with moyamoya disease by brain imaging performed after a head trauma. At the first visit, his best corrected visual acuity was no light perception in the right eye (OD) and 20/25 in the left eye (OS). The intraocular pressure was 8 mmHg (OD) and 10 mmHg (OS). On fundus examination, the right eye showed a dense opacity of an ocular media and the left eye showed no abnormality except an increased cup-to-disc ratio. However, infrared imaging showed multiple whitish lesions in the left eye. Fluorescein angiography showed a patchy choroidal filling delay. During the follow-up, slit-lamp microscopy revealed Lisch nodules and multiple café au lait spots and neurofibromas were found in the skin which led to the diagnosis of NF 1. CONCLUSIONS: When examining patients with moyamoya disease, ophthalmologists should check not only ocular comorbidity associated with moyamoya disease but also ocular comorbidity with other systemic diseases that can accompany moyamoya disease. NF 1 is the most common systemic disease associated with moyamoya syndrome. In this case, appropriate follow-up was essential to monitor the development of ocular or systemic vasculopathies and their complications.
Choroid ; Comorbidity ; Craniocerebral Trauma ; Diagnosis ; Fluorescein Angiography ; Follow-Up Studies ; Humans ; Intraocular Pressure ; Male ; Microscopy ; Middle Aged ; Moyamoya Disease ; Neurofibroma ; Neurofibromatosis 1 ; Neuroimaging ; Skin ; Visual Acuity

Management of large-size retrorectal gastrointestinal stromal tumors (GISTs) is complex and challenging from diagnosis to treatment. This may create technical difficulties in surgical access and complete resection of the tumor. The abdominosacral resection has the benefit of improved visualization via the anterior incision, with enhanced exposure of the midrectal area, which makes resecting the tumor completely via the posterior approach easier. We report 2 cases of patients with a retrorectal GIST and neurofibromatosis type 1, one in a 27-year-old woman with a defecation complaint and the other in a 58-year-old woman with a defecation and urination complaint. Based on the anatomical pathology, both patients were diagnosed with a GIST. The tumors were excised via an abdominosacral resection. Retrorectal GISTs are rare, and abdominosacral resection allows complete resection of a large-size retrorectal GIST with low morbidity and an absence of functional impairment. The abdominosacral resection should be considered in certain situations.
Adult ; Defecation ; Diagnosis ; Disease Management ; Female ; Gastrointestinal Stromal Tumors ; Humans ; Middle Aged ; Neurofibromatosis 1 ; Pathology ; Rectal Neoplasms ; Urination

Kaposiform hemangioendothelioma (KHE) is a very rare, locally aggressive vascular neoplasm. It occurs mostly in children and is rarely observed in adults. It typically originates on the skin, later affecting the deep soft tissue of the extremities, head or neck, and retroperitoneum by infiltrative growth. It is locally aggressive, does not regress spontaneously, and tends to metastasize locally as well as to the regional lymph nodes. In this article, we report a case of adult-onset KHE with neurofibromatosis type 1. The patient presented to our department with a 2-month history of a painful ulceration in her left popliteal area. Since KHE had not previously been reported in patients with neurofibromatosis, the diagnosis was difficult due to the similarity of the skin manifestation to neurofibromatosis-associated lesions. We share our experience of diagnosing and treating this rare case of adult-onset KHE.
Adult ; Child ; Diagnosis ; Extremities ; Head ; Hemangioendothelioma* ; Humans ; Lymph Nodes ; Neck ; Neoplasms, Vascular Tissue ; Neuralgia ; Neurofibromatoses* ; Neurofibromatosis 1* ; Skin ; Skin Manifestations ; Ulcer ; Vascular Neoplasms

Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic disorder caused by NF1 gene mutations. Café au lait spots, neurofibromatosis, Lisch nodules, axillary freckling, dermal neurofibromas and skeletal dysplasia are the most common manifestations for this disease. A 11-year-old boy visited Third Xiangya Hospital, Central South University due to growth-retardation. He was eventually diagnosed as NF1 with growth hormone deficiency. A novel heterozygous splicing mutation c.6579+2 T>C (IVS 34+2 T>C) of NF1 gene was identified in the patient and his mother. Considering NF1 may present with short stature due to growth hormone deficiency, all children with short stature combined with café au lait spots should be screened for NF1, which may assist the clinical diagnosis and the genetic counseling.
Cafe-au-Lait Spots ; diagnosis ; genetics ; Child ; Genes, Neurofibromatosis 1 ; Growth Hormone ; deficiency ; Humans ; Male ; Mutation ; Neurofibromatosis 1 ; blood ; diagnosis

PURPOSE: Solitary plexiform neurofibroma of the eyelid without neurofibromatosis is a rare disease. We report a case of solitary plexiform pigmented neurofibroma of the eyelid without neurofibromatosis. CASE SUMMARY: A 12-year-old male visited our clinic with a painless palpable subcutaneous mass on the right lower eyelid. He had a history of Batter syndrome and attention deficit hyperactivity disorder. On initial presentation, clinical features regarding neurofibromatosis such as Lisch nodule, optic nerve glioma, or high myopia were not observed. We performed excision and biopsy of the lower lid mass under general anesthesia. Macroscopically, the tumor was 4.0 × 1.5 × 1.5 cm in size with irregular nodules. Microscopically, the tumor consisted of multiple, variably sized tortous enlarged nerve fascicles with clusters of pigmented cells. Immunohistochemical results revealed expression of S-100 protein. Pigmented cells express both S-100 and melan-A proteins, while nonpigmented cells express S-100 protein only. The tumor was finally diagnosed as plexiform pigmented neurofibroma. Dermatological evaluation revealed no evidence of systemic neurofibromatosis. CONCLUSIONS: Plexiform neurofibroma should be considered in the differential diagnosis of an eyelid mass, even if the patient does not have a history or clinical features of neurofibromatosis. Plexiform neurofibroma can be successfully managed with surgical excision.
Anesthesia, General ; Attention Deficit Disorder with Hyperactivity ; Biopsy ; Child ; Diagnosis, Differential ; Eyelids* ; Humans ; Male ; MART-1 Antigen ; Myopia ; Neurofibroma ; Neurofibroma, Plexiform* ; Neurofibromatoses ; Neurofibromatosis 1 ; Optic Nerve Glioma ; Rare Diseases ; S100 Proteins

The malignant peripheral nerve sheath tumor (MPNST) originates from neurofibromatosis type 1 (NF1). Because NF1 patients have many accompaniments with growth of additional masses, they usually overlook potential malignant changes in their masses. Our patient had two growing mass near the left elbow for several months; however, she ignored these masses until 7 days prior to writing this article, at which time they began bleeding. Traditionally, sarcoma including MPNST treatment consisted of amputation of the involved extremity. However, treatment now consists of surgical resection with adjuvant therapy. Therefore, we conducted resection of the mass and subsequent coverage with a local advancement flap. We believe that the most effective treatment for MPNST is early diagnosis and fast surgery, coupled with notification that there is always potential for malignant change in NF1 patient's masses.
Amputation ; Diagnosis ; Drug Therapy ; Early Diagnosis ; Elbow ; Extremities ; Hemorrhage ; Humans ; Neurilemmoma ; Neurofibromatoses* ; Neurofibromatosis 1* ; Peripheral Nerves* ; Sarcoma ; Writing