TaoMedAI/RareMedData huggingface dataset:
Neurodegeneration with brain iron accumulation (ORPHA:385)
Neurodegeneration with brain iron accumulation (NBIA, formerly Hallervorden-Spatz syndrome) encompasses a group of rare neurodegenerative disorders characterized by progressive extrapyramidal dysfunction (dystonia, rigidity, choreoathetosis), iron accumulation in the brain and the presence of axonal spheroids, usually limited to the central nervous system.
Epidemiology
An estimated prevalence of 1-3/1,000,000 has been suggested based on observed cases in a population. The most common form of NBIA is pantothenate kinase-associated neurodegeneration (PKAN; see this term), which accounts for approximately 50% of cases.
Clinical description
NBIA can present as early onset with rapid progression: classic pantothenate kinase-associated neurodegeneration (PKAN), infantile neuroaxonal dystrophy (INAD) and atypical neuroaxonal dystrophy (atypical NAD) (see these terms); or later onset with slower progression: atypical PKAN, neuroferritinopathy and aceruloplasminemia (see these terms). Idiopathic NBIA can have either type of onset and progression.
Etiology
Classic and atypical PKAN are caused by mutations in the PANK2 gene (20p13-p12.3), infantile and atypical neuroaxonal dystrophy are caused by mutation in the PLA2G6 gene (22q13.1), aceruloplasminemia is caused by mutation of the ceruloplasmin (CP) gene (3q23-q24) and neuroferritinopathy is caused by mutations in the ferritin light chain (FTL1) gene (19q13.3-q13.4). Idiopathic NBIA is likely caused by several additional, as yet undiscovered genes.
Diagnostic methods
This heterogeneous group of disorders can be differentiated by clinical, radiographic, and molecular features. Brain MRI is standard in the diagnostic evaluation of all forms of NBIA. Individuals with PKAN and HARP syndrome, which is considered part of the PKAN disease spectrum, show a characteristic "eye of the tiger''sign on MRI, a central region of hyperintensity surrounded by a rim of hypointensity on coronal or transverse T2-weighted images of the globus pallidus. Infantile and atypical NAD have characteristic axonal swellings throughout the central and peripheral nervous system. Diagnosis of aceruloplasminemia is based on the absence of serum ceruloplasmin in combination with MRI findings of iron accumulation.
Genetic counseling
The majority of NBIA types are transmitted in an autosomal recessive manner, except neuroferritinopathy which is transmitted in an autosomal dominant manner with high penetrance.
Management and treatment
At this time most treatments for NBIA are palliative. Research is currently underway to identify additional NBIA genes and improve treatment possibilities by characterizing the underlying causes of these disorders.

                            Last update: 
                            March 2010


                            - Expert reviewer(s): 
                            Dr Allison GREGORY  - Pr Susan HAYFLICK
Neurodevelopmental delay-seizures-ophthalmic anomalies-osteopenia-cerebellar atrophy syndrome (ORPHA:529665)
A rare, genetic, syndromic intellectual disability characterized by global developmental delay, early-onset seizures, cerebellar atrophy, osteopenia, nystagmus and dysmorphic facial features, including bitemporal narrowing, prominent forehead, anteverted nares. Dysarthria, dysmetria, ataxic gait, spasticity and dysmorphic features have also been associated.
Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome (ORPHA:453499)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, intellectual disability, hypotonia, craniofacial dysmorphism (such as ridged metopic sutures, long palpebral fissures, broad nasal bridge, hypoplastic alae nasi, low-set, prominent ears, prominent midline tongue groove, and downturned mouth), congenital heart defects, and variable skeletal abnormalities including hip dysplasia, vertebral anomalies, and scoliosis. Additional reported manifestations include high pain tolerance and genitourinary anomalies. Brain imaging may show a thin corpus callosum or white matter abnormalities.
Neuroendocrine carcinoma of pancreas (ORPHA:506098)
A rare neuroendocrine neoplasm of pancreas characterized by a high-grade malignant epithelial tumor with neuroendocrine differentiation. Based on histopathologic appearance, a small cell (composed of diffuse sheets of cells) and a large cell type (showing a nesting/trabecular pattern) are distinguished. Synaptophysin and chromogranin are positive on immunohistochemistry. The Ki-67 proliferation index is typically very high (>60 - 80%). Patients present with back pain, jaundice, and/or non-specific abdominal symptoms. Serum hormone activity is unusual. The tumor is highly aggressive with poor prognosis.
Neuroendocrine cell hyperplasia of infancy (ORPHA:217560)
Neuroendocrine cell hyperplasia of infancy (NCHI) is a non-lethal pediatric form of interstitial lung disease (ILD, see this term) characterized by tachypnea without respiratory failure.
Epidemiology
Prevalence of this disease is not known. It appears to affect young infants (mean age 3.8 months found in a large series) but cases have been reported in older children.
Clinical description
Clinical presentation is typically persistent tachypnea.
Etiology
High-resolution computed tomography (HRCT) shows patchy central ground-glass opacifications and air trapping. Lung biopsy shows hyperplasia of neuroendocrine cells within bronchioles documented by bombesin immunohistochemistry.
Management and treatment
Follow-up reveals in some cases the persistence of tachypnea and oxygen requirement for several months.
Prognosis
The prognosis is usually good.

                            Last update: 
                            January 2011


                            - Expert reviewer(s): 
                            Pr Annick CLEMENT
Neuroendocrine neoplasm of appendix (ORPHA:100079)
A rare sporadic neoplasm of the appendix and the second most common type of digestive endocrine tumor, often with no specific clinical presentation. They are divided into either classic endocrine tumor of the appendix or the more aggressive goblet cell carcinoma (GCC).
Neuroendocrine neoplasm of esophagus (ORPHA:506136)
A group of esophageal epithelial neoplasms characterized by neuroendocrine differentiation, comprising well-differentiated neuroendocrine tumors (NETs), poorly differentiated neuroendocrine carcinomas (NECs), and mixed neuroendocrine-non-neuroendocrine neoplasms, an umbrella category including mixed adenoneuroendocrine carcinoma. The tumors typically occur in the lower esophagus, often in association with Barrett mucosa. NECs may also arise in other parts of the esophagus. On endoscopy, NETs usually appear as small polypoid or nodular submucosal masses, while NECs are large, infiltrative, and ulcerated. Patients most commonly present with dysphagia, pain, weight loss, and sometimes melena. Metastatic NETs may be associated with carcinoid syndrome.
Neuroendocrine neoplasm (ORPHA:877)
A group of rare tumors characterized by predominantly neuroendocrine differentiation, potentially arising in most organs of the body, including the central nervous system, respiratory tract, larynx, gastrointestinal tract, thyroid, skin, breast, and urogenital system. The gastrointestinal tract and lungs are the most common primary tumor sites. Based on clinical behavior, histology, and proliferation rate, the tumors may be categorized as well differentiated (low grade to intermediate grade) neuroendocrine tumors and poorly differentiated (high grade) neuroendocrine carcinomas. They may or may not be associated with clinical hormone hypersecretion syndromes.
Neuroendocrine tumor of anal canal (ORPHA:100082)
A are epithelial tumor of the anal canal arising from enterochromaffin cells in the colorectal-type epithelium above the dentate line and in the anal transition zone. The tumors are slow growing and the majority of cases are diagnosed in later advanced stages. It may present with symptoms related to the anatomical location of the tumor (rectal mass, rectal bleeding and pain, tenesmus or changes in bowel habits), symptoms of carcinoid syndrome (flushing and increased gut motility) or nonspecific symptoms of advanced disease (hepatomegaly, fever, weight loss, anorexia, malaise).
Neuroendocrine tumor of stomach (ORPHA:100075)
A rare subtype of neuroendocrine neoplasm, arising from enterochromaffin-like cells in the stomach, with a variable clinical presentation, disease course and prognosis, depending on the disease type and histological grade. Most patients are asymptomatic, with diagnosis usually occurring incidentally during gastroscopy, however, symptoms of dyspepsia, anemia, pain, weight loss and gastrointestinal bleeding can be observed. Association with Zollinger-Ellison syndrome and multiple endocrine neoplasia type I has been reported.
Neuroendocrine tumor of the colon (ORPHA:100080)
A rare epithelial tumor of the large intestine, arising from enterochromaffin cells, most commonly in the cecum or ascending colon. The tumor is usually slow-growing and can be diagnosed as an incidental finding in an asymptomatic patient, while in the later stages patients can present with abdominal pain, palpable abdominal mass, changes in bowel habits, signs of bowel obstruction, gastrointestinal bleeding, anorexia, weight loss or, rarely, carcinoid syndrome (facial flushing, diarrhea, tachycardia, hypo- and hypertension, cardiac abnormalities).
Neuroendocrine tumor of the rectum (ORPHA:100081)
Neuroendocrine tumor of the rectum is a rare epithelial tumor of rectum arising from enterochromaffin cells, most often in the mid-rectum. The tumors are slow growing, in early stages majority are asymptomatic and are diagnosed incidentally. Later in the course, the tumor may present with rectal bleeding, abdominal or rectal pain, tenesmus, changes in bowel habits, or weight loss. In some cases it may present with carcinoid symptoms of flushing and increased gut motility.
Neurofaciodigitorenal syndrome (ORPHA:2673)
Neurofaciodigitorenal syndrome is a rare multiple developmental anomalies syndrome characterized by neurological abnormalities (including megalencephaly, hypotonia, intellectual disability, abnormal EEG), dysmorphic facial features (high prominent forehead, grooved nasal tip, ptosis, ear anomalies) and acrorenal defects (such as triphalangism, broad halluces, unilateral renal agenesis). Additionally, intrauterine growth restriction, short stature and congenital heart defects may be associated. There have been no further descriptions in the literature since 1997.
Neurofibroma (ORPHA:252183)
A rare benign peripheral nerve sheath tumor characterized by a well-demarcated intraneural or diffusely infiltrative extraneural space-occupying lesion consisting of Schwann cells, perineurial-like cells, and fibroblasts. It presents as a cutaneous nodule, a circumscribed mass in a peripheral nerve, a plexiform enlargement of a major nerve trunk, or with diffuse but localized involvement of skin and subcutaneous tissue. Multiple neurofibromas are typically associated with neurofibromatosis 1. Malignant transformation occurs almost exclusively in plexiform neurofibromas and neurofibromas of major nerves.
Neurofibromatosis-Noonan syndrome (ORPHA:638)
Neurofibromatosis-Noonan syndrome (NFNS) is a RASopathy and a variant of neurofibromatosis type 1 (NF1) characterized by the combination of features of NF1, such as café-au-lait spots, iris Lisch nodules, axillary and inguinal freckling, optic nerve glioma and multiple neurofibromas, and Noonan syndrome (NS), such as short stature, typical facial features (hypertelorism, ptosis, downslanting palpebral fissures, low-set posteriorly rotated ears with a thickened helix, and a broad forehead), congenital heart defects and unusual pectus deformity. As these three entities have significant phenotypic overlap, molecular genetic testing is often necessary for a correct diagnosis (such as when café-au-lait spots are present in patients diagnosed with NS).
Neurogenic arthrogryposis multiplex congenita (ORPHA:1143)
A form of arthrogryposis multiplex congenita characterized by congenital immobility of the limbs with fixation of multiple joints and muscle wasting. This condition is secondary to neurogenic muscular atrophy.
Neurogenic scapuloperoneal syndrome, Kaeser type (ORPHA:85146)
A rare, genetic, neuromuscular disease characterized by adult-onset muscle weakness and atrophy in a scapuloperoneal distribution, mild involvement of the facial muscles, dysphagia, and gynecomastia. Elevated serum CK levels and mixed myopathic and neurogenic abnormalities are associated clinical findings.
Neurogenic thoracic outlet syndrome (ORPHA:100073)
Neurogenic thoracic outlet syndrome (NTOS) is a form of thoracic outlet syndrome (TOS; see this term) that presents with pain, paresthesias and weakness in an upper extremity and is divided into true NTOS and disputed NTOS.
Epidemiology
The incidence of NTOS is unknown. It affects women more than men. Disputed NTOS is the most controversial form and accounts for approximately 95% of all cases of TOS and 99% of cases with neurologic symptoms
Clinical description
NTOS presents with upper extremity paresthesias, pain and weakness. True NTOS manifests slowly with the progressive unilateral atrophic weakness of the intrinsic hand muscles and sensory abnormalities in a T1 distribution due to a lower trunk brachial plexopathy. Disputed NTOS does not cause muscle atrophy, but there is scalene muscle tenderness and symptoms worsen with arm use and provocative maneuvers.
Etiology
True NTOS is caused by lower trunk brachial plexus compression in the thoracic outlet at the interscalene triangle, costoclavicular space, or subcoracoid space deep to the pectoralis minor tendon. Disputed NTOS may be due to scarring of scalene muscles, poor posture or a congenital anomaly.
Diagnostic methods
Radiographs may identify compressive sources including an elongated C7 transverse process or anomalous first rib. Electrodiagnostic (EDX) findings demonstrate a lower trunk brachial plexopathy. MRI identifies compressive sources and rules out other causes such as a Pancoast tumor. Disputed NTOS is a clinical diagnosis that depends on scalene muscle tenderness and provocative maneuvers eliciting pain and paresthesias in the affected extremity as it lacks objective EDX evidence. It is most often a diagnosis of exclusion.
Differential diagnosis
Differential diagnoses include arterial and venous TOS (see these terms), cervical radiculopathy, carpal tunnel syndrome or any disorder involving nerve fibers derived from C8 or T1 nerve roots such as cubital tunnel syndrome. EDX testing differentiates the lower trunk brachial plexopathy of NTOS from other neurologic diagnoses. Arterial TOS presents with ischemia and venous TOS presents with venous congestion.
Management and treatment
Disputed NTOS is treated with physical therapy, medication and use of orthoses and neck collars. Refractory cases may undergo surgical decompression. For true NTOS surgical decompression is considered based on the degree of nerve injury and is indicated if there is acute or sub-acute progressive weakness or disabling pain and paresthesias.
Prognosis
In cases of true NTOS, decompression relieves pain, but full neurologic recovery requires time for remyelination or axonal regeneration. If there is axonal loss, recovery may be incomplete. Success rates for surgical decompression of disputed NTOS are 91%-93% immediately after treatment, but drop to 64% to 71% after 10 years due to a high rate of recurrence.

                            Last update: 
                            May 2013


                            - Expert reviewer(s): 
                            Dr Joseph FEINBERG  - Dr Paul SCHOLTEN
Neurolymphomatosis (ORPHA:206586)
Neurolymphomatosis is a rare syndrome of peripheral and cranial nerve dysfunction in patients with hematologic malignancies, mostly non-Hodgkin's lymphoma or acute leukemia, characterized by painful or painless involvement of peripheral or cranial nerves or nerve roots. The clinical presentation is diverse depending on the site involved and includes plexopathy, mononeuritis multiplex, peripheral neuropathy, radiculopathy and cranial nerve palsies.
Neurometabolic disorder due to serine deficiency (ORPHA:35705)
Serine-deficiency syndrome is a very rare infantile-onset potentially treatable neurometabolic disorder characterized clinically by microcephaly, neurodevelopmental disorders and seizures. Three serine-deficiency syndromes have been described: 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency, 3-phosphoserine phosphatase (3-PSP) deficiency, and phosphoserine aminotransferase deficiency (see these terms).
Neuronal ceroid lipofuscinosis (ORPHA:216)
Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited progressive degenerative brain diseases characterized clinically by a decline of mental and other capacities, epilepsy, and vision loss through retinal degeneration, and histopathologically by intracellular accumulation of an autofluorescent material, ceroid lipofuscin, in the neuronal cells in the brain and in the retina.
Epidemiology
The exact prevalence and incidence of this group of disorders are unknown.
Clinical description
The clinical presentation varies widely between forms but the clinical hallmark is a combination of dementia, visual loss, and epilepsy. Manifestations may begin between the neonatal period and young adult age depending on the form, leading to the original classification of NCLs by age at onset into congenital, infantile, late infantile, juvenile and adult NCL subgroups (see these terms). A Northern epilepsy variant (progressive epilepsy-intellectual deficit, Finnish type; see this term), in which the visual problems may be absent or be mild and go unrecognized, has also been described.
Etiology
To date, at least 10 genetic NCL disorders have been reported and are designated as CLN1 to CLN10. The majority of NCLs are inherited in an autosomal recessive manner, however, autosomal dominant inheritance has been reported in one adult-onset form designated as a CLN4 disease.
Diagnostic methods
Diagnosis is based on clinical findings, electron microscopy studies revealing storage material with autofluorescent ceroid lipopigments, and enzymatic testing for deficiencies in palmitoyl-protein thioesterase 1, tripeptidyl-peptidase 1 and cathepsin D, present in patients with the CLN1, CLN2 and CLN10 diseases, respectively. With the exception of the CLN4 and CLN9 diseases (for which the causative genes have not yet been identified), the diagnosis can be confirmed by molecular testing.
Differential diagnosis
The differential diagnoses should include other causes of vision loss, dementia and seizures with an appropriate age of onset (typically mitochondrial disorders, inborn errors of metabolism and other lysosomal storage disorders).
Antenatal diagnosis
Prenatal diagnosis is feasible through molecular testing if the disease-causing mutation in the family has already been identified or through enzymatic analysis in some cases.
Management and treatment
There is no curative treatment for NCLs and management is supportive only.
Prognosis
Although all NCLs lead to severe disability, the prognosis is variable with life expectancy ranging from a few hours or days after birth for the congenital form to survival into the fifth decade for patients with the adult-onset form.

                            Last update: 
                            February 2010


                            - Expert reviewer(s): 
                            Pr Alfried KOHLSCHÜTTER
Neuronal intestinal pseudoobstruction (ORPHA:99811)
Neuronal intestinal pseudoobstruction is a form of chronic intestinal pseudoobstruction caused by a developmental failure of the enteric neurons to differentiate or migrate properly and manifests as a bowel obstruction.
Neuronal intranuclear inclusion disease (ORPHA:2289)
Neuronal intranuclear inclusion disease (NIID) is a very rare multisystem neurodegenerative disorder characterized by the presence of eosinophilic intranuclear inclusions in neuronal and glial cells, and neuronal loss.
Epidemiology
Infantile, juvenile, and adult-onset cases have been described in approximately 30 patients word-wide.
Clinical description
As any part of the nervous system can be affected (central, peripheral, and autonomic nervous systems), the clinical manifestations depend on the sites involved, and widely vary. The most common neurological signs include ataxia, extra-pyramidal signs (tremor and oculogyral crises), lower motor neuron findings (absent deep tendon reflexes, weakness, muscle wasting, foot deformities), and less apparent behavioural or cognitive difficulties. Dementia is reported as a predominant neurological symptom in adult patients, while infantile/juvenile cases show disproportionate ataxia and other movement symptoms. Occasionally, gastrointestinal dysmotility with severe weight loss may be present, if the enteric nervous system is involved.
Diagnostic methods
NIID may be diagnosed by a full thickness rectal biopsy.
Differential diagnosis
The differential diagnosis should consider spinocerebellar ataxias, progressive juvenile parkinsonism and dystonia.
Genetic counseling
Most cases are sporadic. Despite reports of several familial cases (including a pair of identical twins), no causative gene has been identified. Autosomal dominant transmission has been suggested in these families.
Management and treatment
There is no cure or treatment that slows the progression of the disease. Symptomatic treatments may improve the quality of life.
Prognosis
NIID is slowly progressive (within 10 to 20 years) and fatal.

                            Last update: 
                            April 2007


                            - Expert reviewer(s): 
                            Pr Bertrand FONTAINE
Neuropathy with hearing impairment (ORPHA:139512)
This syndrome is characterized by the association of sensorineural hearing impairment and peripheral neuropathy.
Epidemiology
It has been described in members from four generations of a Spanish family.
Clinical description
The hearing impairment was mild and often asymmetrical. The neuropathy was demyelinating with predominantly sensory involvement but severity was variable ranging from asymptomatic individuals to patients with skin ulcers and osteomyelitis requiring amputation.
Etiology
Neuropathy with hearing impairment is caused by mutations in the GJB3 gene (1p34).
Genetic counseling
The syndrome is transmitted in an autosomal dominant manner.

                            Last update: 
                            January 2009