TaoMedAI/RareMedData huggingface dataset:
Nanophthalmos (ORPHA:35612)
A rare ophthalmic disease and a severe form of microphthalmia (small eye phenotype) characterized by a small eye with a short axial length, severe hyperopia, an elevated lens/eye ratio, and a high incidence of angle-closure glaucoma.
Epidemiology
The exact prevalence of nanophthalmos is unknown but is likely to be below 1/2,000. However, the prevalence is higher among consanguineous populations.
Clinical description
The disease occurs neonatally or during infancy. Typical clinical signs include an axial length inferior to 20 mm, a lens/eye ratio 4 to 8 times greater than normal, thickened and abnormally dense sclera, a thickened lens and choroids, and severe hyperopia (+7.00 D to +13.00 D). Despite its small size, the functionality and organization of the eye are preserved. Nanophthalmos is generally bilateral. Strabismus is present in most patients. The association of nanophthalmos and pigmentary retinopathy or Best disease has been reported. The condition can be simple (occurring in isolation), complex (associated with other malformations such as colobomas, anterior segment dysgenesis, and lens and posterior segment abnormalities) or syndromic (as part of a rare syndrome).
Etiology
To date, five genes have been associated with the disease : MFRP (11q23.3, coding for a frizzled protein playing a role in the regulation of cell growth, differentiation and polarity during development), TMEM98 (17q11.2, coding for an ubiquitous protein which could be involved in the scleral pathologic thickening and secondary glaucoma development in the disease), PRSS56 (2q37.1, the exact physiopathological mechanism is unknown), BEST1 (11q12.3, involved for example in the development of angle-closure glaucoma) and CRB1 (1q31.3, coding for a protein essential for the neuronal development of the retina). Other loci are also associated with nanophthalmos.
Diagnostic methods
Diagnosis is based on clinical findings and ophthalmologic examinations involving ocular biometry, ultrasonography, as well as corneal diameter and intraocular pressure measurements.
Differential diagnosis
Nanophthalmos should be differentiated from posterior microphthalmos.
Genetic counseling
The disease may be inherited as an autosomal dominant or recessive trait. It can also occur sporadically.
Management and treatment
Treatment may include surgery (iridotomy, iridoplasty, glaucoma filtering surgery, and lens extraction), but side effects (malignant glaucoma, uveal effusion, nonrhegmatogenous retinal detachment and expulsive hemorrhage) may occur. Complications can be prevented by performing a sclerectomy before any intraocular intervention.
Prognosis
Angle-closure glaucoma is a constant finding in patients with nanophthalmia but the prognosis is favorable if this manifestation is correctly managed.

                            Last update: 
                            October 2019


                            - Expert reviewer(s): 
                            Pr Alain BRON  - Pr Paul FOSTER
Narcolepsy type 1 (ORPHA:2073)
A rare neurologic disease characterized by excessive daytime sleepiness associated with uncontrollable sleep urges and cataplexy (sudden loss of muscle tone while awake, often triggered by pleasant emotions).
Epidemiology
Narcolepsy type 1 prevalence is estimated between 1/2,000 and 1/5,000.
Clinical description
The age of onset varies between 10 and 30 years old and symptoms are lifelong. The average time between the age of appearance of the symptoms and the diagnosis is still very long, 10 years. Other, non specific, clinical signs include hypnagogic hallucinations, sleep paralysis, disturbed nocturnal sleep, and weight gain, especially in children.
Etiology
The disease is due to loss or impairment of the orexin/hypocretin neurons of the lateral hypothalamus that results in decreased hypocretin-1 levels in the cerebrospinal fluid. An autoimmune origin for the disease is highly suspected, particularly environmental factors interacting with susceptibility genes (more than 98% of the patients carry the HLA-DQB1*0602 allele); however, this is unproven.
Diagnostic methods
Definitive diagnosis requires the presence of clinical symptoms, characteristic polysomnography findings and/or low hypocretin-1 levels in cerebral spinal fluid. Nocturnal and daytime polysomnography demonstrate an average sleep latency of under eight minutes with at least two sleep onset rapid eye movement periods (SOREMP) on multiple sleep latency tests. The presence of low hypocretin-1 levels (<110 pg/ml) in the cerebrospinal fluid can confirm the diagnosis with an excellent sensibility and specificity.
Differential diagnosis
Cataplexy must be typical to be confident with the diagnosis. In absence of typical cataplexy, other causes of sleepiness must be considered, such as chronic insufficient sleep, idiopathic hypersomnia or narcolepsy without cataplexy, now called narcolepsy type 2.
Genetic counseling
Rare familial cases have been reported (<2%); however the mode of inheritance is unclear.
Management and treatment
Treatment is nowadays only symptomatic, as the loss of orexin neurons is irreversible. It comprises stimulants (modafinil, methylphenidate, amphetamine, pitolisant, solriamfetol), anticataplectic drugs (antidepressants) or sodium oxybate. First-line treatment of diurnal sleepiness is often with modafinil but it can be also with pitolisant or sodium oxybate. Second-line treatments are methylphenidate, solriamfetol or amphetamines. Sodium oxybate is efficient for sleepiness, cataplexy and disturbed nocturnal sleep. A good sleep hygiene is always recommended, with scheduled short naps, and regular sleep habits.
Prognosis
Narcolepsy can severely disable scholarly and professional performances. The evolution of the disease is often stable with a frequent improvement of sleepiness and cataplexy, but with age there is an aggravation of the poor quality of night sleep.

                            Last update: 
                            November 2020


                            - Expert reviewer(s): 
                            Dr Lucie BARATEAU  - Pr Yves DAUVILLIERS
Narcolepsy type 2 (ORPHA:83465)
A rare neurologic disease characterized by excessive daytime sleepiness associated with uncontrollable sleep urges and sometimes sleep paralysis, and hypnagogic/hypnopompic hallucinations.
Epidemiology
No clear epidemiological data are available. Narcolepsy type 2 prevalence numbers are controversial, sometimes higher and sometimes lower than those of narcolepsy type 1, depending on reports.
Clinical description
Narcolepsy type 2 manifests generally between the age of 10 and 30 years old, although onset in childhood is rare. Narcolepsy type 2 has a variable phenotype and evolution, with sometimes improvement or even disappearance of the symptoms, rarely the development of cataplexy (conversion to narcolepsy type 1), or a change in the phenotype to idiopathic hypersomnia. It can also be a lifelong disease, with stable symptomatology.
Etiology
The etiology is still unknown, probably because this disorder is heterogeneous. Reduction of hypocretin-1 levels is found in the cerebrospinal fluid in 10-20% of cases, and in which case the disorder is reclassified narcolepsy type 1. The presence of the HLA DQB1*0602 allele is reported in 40% of cases (more than in the general population but less than in cases of narcolepsy type 1, 98%).
Diagnostic methods
Definitive diagnosis requires the presence of clinical symptoms and characteristics polysomnography findings. Nocturnal and daytime polysomnography demonstrates an average sleep latency of under eight minutes with at least two sleep onset rapid eye movement periods (SOREMP) on multiple sleep latency tests. A pure clinical diagnosis is not possible due to the absence of pathognomonic symptom such as cataplexy, and daytime sleepiness being a non-specific symptom.
Differential diagnosis
Other causes of sleepiness, including narcolepsy type 1, chronic insufficient sleep and idiopathic hypersomnia (especially the form without long sleep time), must be systematically taken into account.
Genetic counseling
Rare familial cases have been reported; however, the mode of inheritance is unclear.
Management and treatment
Treatment is only symptomatic, based on stimulant drugs and a good sleep hygiene (sufficient sleep duration at night is required, with scheduled short naps during the day). Modafinil or pitolisant are the first line treatments with the best benefit/risk ratio. Second-line treatments include methylphenidate, sodium oxybate, solriamfetol or amphetamines.
Prognosis
The disease has a negative impact on scholarly and professional performances. Spontaneous evolution of the disease has not been much studied, but the phenotype and evolution seems variable : stability, disappearance of the symptoms, development of cataplexy (conversion to narcolepsy type 1) , or change to idiopathic hypersomnia.

                            Last update: 
                            November 2020


                            - Expert reviewer(s): 
                            Dr Lucie BARATEAU  - Pr Yves DAUVILLIERS
Nasal dermoid cyst (ORPHA:141103)
A rare otorhinolaryngological malformation characterized by a dermoid cyst along the nasal dorsum or glabella, lined by keratinized squamous epithelium and containing intraluminal keratin and mature adnexal structures, such as hair follicles, sebaceous and sweat glands. The majority of nasal dermoid cysts are superficial, rarely they extend intracranially. The cysts are typically benign but are susceptible to recurrent infections that may progress to osteomyelitis, meningitis or an intracranial abscess.
Nasal dorsum fistula (ORPHA:141219)
A rare otorhinolaryngological malformation characterized by the presence of a dermoid cyst, located on the dorsum of the nose, which presents a fistula, often extending to the intracranial region. Patients present a firm, slow-growing mass, which contains skin and dermal elements (including hair follicles and sebaceous glands), that do not transilluminate or compress, and may be associated with intermittent or chronic discharge of sebaceous material, soft tissue and skeletal deformity, and local infection. Meningitis, convulsions and cerebral abscess may be observed if intracranial extension exists.
Nasal encephalocele (ORPHA:141118)
Nasal encephalocele is an extracranial herniation of intracranial contents (that maintain a connection to the subarachnoid space) into the fonticulus frontalis, presenting with nasal broadening and/or as a compressible, blue, pulsatile mass near the nasal bridge (that enlarges on crying or with jugular vein compression) or as an intranasal mass originating in the cribiform plate and that can cause nasal obstruction or respiratory distress. Hydrocephalus and increased intracranial pressure are also reported in some cases.
Nasal ganglioglioma (ORPHA:141115)
Nasal ganglioglioma is a rare tumor, presenting in newborns, containing both neuronal and astrocytic components and that can be endonasal, extranasal or both. It is usually identified as a nasal mass that may cause feeding difficulties and nasal obstruction.
Nasal glial heterotopia (ORPHA:141112)
Nasal glial heterotopia is a rare developmental abnormality presenting usually at birth or in early childhood (rarely in adulthood) as a benign, non-pulsatile mass that can lead to nasal obstruction, deformation of the septum and nasal bone, and respiratory distress if untreated. Nasal glial heterotopias have no communication with the central nervous system; however an associated defect in the cribriform plate is sometimes reported.
Nasolacrimal duct cyst (ORPHA:141083)
Nasolacrimal duct cyst describes a unilateral or bilateral congenital cyst of the nasolacrimal duct, which is almost always associated with dacryocystocele, presenting most commonly at birth or a few weeks of age (but rarely presenting in adulthood) as a benign, grayish blue mass in the inferomedial canthus or in the nasal cavity, that can cause epiphora, dacryocystitis (inflammation of the lacrimal sac) and nasal obstruction. It is more commonly reported in females.
Nasopalpebral lipoma-coloboma syndrome (ORPHA:2399)
A rare multiple congenital anomalies syndrome characterized by nasopalpebral lipomas, bilateral lid coloboma, and telecanthus.
Epidemiology
Nasopalpebral lipoma-coloboma-telecanthus syndrome (NPLCS) is a very rare syndrome. About 20 patients from 5 families were reported in the literature.
Clinical description
NPLCS is characterized by a congenital facial malformation associating bilateral upper eyelid and nasopalpebral lipomas, colobomas of upper and lower eyelids, telecanthus, and maxillary hypoplasia. Additional features may include displaced or aplastic lacrimal punctae, epiphora, aberrant eyelashes, conjunctival hyperemia, corneal and lens opacities, strabismus, nanophtalmos, limbal dermoid, dysplastic ears and nasopalpebral hamartomas. No extra-facial abnormalities are described.
Etiology
A heterozygous frameshift variant in the zinc finger transcription factor, encoded by ZDBF2 (2q33.3) has been identified in one sporadic patient. However, no functional studies were published to support the pathogenicity of this variant and no further patients have been reported since.
Diagnostic methods
The diagnostic is based on clinical examination.
Differential diagnosis
The main differential diagnoses include congenital infiltrating lipomatosis of the face, oculocerebrocutaneous syndrome, and conditions with eyelid coloboma and hypertelorism such as frontonasal dysplasia, craniofrontonasal syndrome, and oculoauriculofrontonasal syndrome.
Antenatal diagnosis
Genetic prenatal diagnosis is not available since the molecular basis is unknown.
Genetic counseling
Vertical, male-to-male transmission in 3 and 4 generations suggests autosomal dominant mode of inheritance with complete penetrance. Genetic counseling should be offered to affected families.
Management and treatment
Plastic and reconstructive surgery can be performed, notably excision of the lipomas and eyelid coloboma repair.
Prognosis
There are limited data in the literature regarding the prognosis of the affected individuals. Cognitive development seems to be normal.

                            Last update: 
                            September 2020


                            - Expert reviewer(s): 
                            Pr Laurence OLIVIER-FAIVRE | ITHACA*


                                * European Reference Network
Nasopharyngeal carcinoma (ORPHA:150)
Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx.
Epidemiology
The annual incidence is around 1/100 000 in Western countries. Incidence is higher in the Chinese and Tunisian populations. Although rare, NPC accounts for about one third of childhood nasopharyngeal neoplasms.
Clinical description
Three subtypes of NPC are recognized in the World Health Organization (WHO) classification: 1) squamous cell carcinoma, typically found in the older adult population; 2) non-keratinizing carcinoma; 3) undifferentiated carcinoma. The tumor can extend within or out of the nasopharynx to the other lateral wall and/or posterosuperiorly to the base of the skull or the palate, nasal cavity or oropharynx. It then typically metastases to cervical lymph nodes. Cervical lymphadenopathy is the initial presentation in many patients, and the diagnosis of NPC is often made by lymph node biopsy. Symptoms related to the primary tumor include trismus, pain, otitis media, nasal regurgitation due to paresis of the soft palate, hearing loss and cranial nerve palsies. Larger growths may produce nasal obstruction or bleeding and a 'nasal twang'.
Etiology
Etiological factors include Epstein-Barr virus (EBV), genetic susceptibility and consumption of food with possible carcinogens - volatile nitrosamines.
Diagnostic methods
Diagnostic methods include indirect nasopharyngoscopy to assess the primary tumor, clinical evaluation of the size of cervical lymph nodes and biopsy of either the lymph nodes or primary tumor for histological examination. Other potential sites of metastasis are further investigated by neurological examination of cranial nerves, computed tomography (CT)/magnetic resonance imaging (MRI) scan of the head and neck, chest radiotherapy and bone scintigraphy. EBV viral capsid antigen and EBV DNA can be detected by serum analysis.
Management and treatment
The recommended treatment schedule consists of three courses of neoadjuvant chemotherapy, irradiation, and adjuvant interferon (IFN)-beta therapy.
Prognosis
Presentation with lymphadenopathy implies that the disease has spread beyond the primary site. However, in childhood, the presence of metastatic disease in cervical lymph nodes at diagnosis does not adversely affect prognosis. Factors associated with a poor prognosis are skull base involvement, extent of the primary tumor and cranial nerve involvement.

                            Last update: 
                            July 2006


                            - Expert reviewer(s): 
                            Pr Bernadette BRENNAN
Nathalie syndrome (ORPHA:2663)
A rare, genetic developmental defect during embryogenesis disorder characterized by sensorineural hearing impairment, childhood-onset cataract, underdeveloped secondary sexual characteristics, spinal muscular atrophy, growth retardation, and cardiac and skeletal anomalies. Sudden death, as well as fatal cardiomyopathy and heart failure, have been described in some cases.
Native American myopathy (ORPHA:168572)
Native American myopathy (NAM) is a neuromuscular disorder characterized by weakness, arthrogryposis, kyphoscoliosis, short stature, cleft palate, ptosis and susceptibility to malignant hyperthermia during anesthesia.
Epidemiology
NAM is reported exclusively in Native American Indians (Lumbee Indian population of North Carolina). Within this population, the prevalence of NAM is estimated at approximately 1:5,000.
Etiology
The NAM locus has been localized to 12q13.13-14.1.
Genetic counseling
The disease is transmitted in an autosomal recessive manner.

                            Last update: 
                            February 2009
Navajo neurohepatopathy (ORPHA:255229)
A rare, life-threatening, mitochondrial DNA depletion syndrome disease characterized by severe, progressive sensorimotor neuropathy associated with corneal ulceration, scarring or anesthesia, acral mutilation, metabolic and immunologic derangement, and hepatopathy (which can manifest with fulminant hepatic failure, a Reye-like syndrome or indolent progression to liver cirrhosis, depending on clinical form involved), present in the Navajo Native American population. Clinical presentation includes failure to thrive, distal limb weakness with reduced sensation, limb contractures with loss of function, areflexia, recurrent metabolic acidosis with intercurrent illness, immunologic anomalies manifesting with severe systemic infections, and sexual infantilism.
NDE1-related microhydranencephaly (ORPHA:443162)
NDE1-related microhydranencephaly is a rare, hereditary syndrome with a central nervous system malformation as major feature characterized by extreme microcephaly and growth restriction, severe motor delay and mental retardation, and typical radiological findings of gross dilation of the ventricles resulting from the absence (or severe delay in the development) of cerebral hemispheres, hypoplasia of the corpus callosum, cerebellum, and brainstem. Associated features are thin bones and scalp rugae.
Necrobiosis lipoidica (ORPHA:542592)
A rare skin disease characterized by enlarging, annular plaques with red-brown edges and atrophic, yellow-brown, telangiectatic centers. The lesions are commonly asymptomatic, but affected skin areas may be fragile, and painful ulcerations develop in many cases. In rare cases, development of squamous cell carcinoma within longstanding lesions has been reported. The lower legs, especially the shins, are the most frequently involved site. The condition is often associated with diabetes mellitus.
Necrobiotic xanthogranuloma (ORPHA:158011)
Necrobiotic xanthogranuloma is a rare, chronic and progressive, non-Langerhans cell histiocytosis disease typically characterized by multiple, indurated, asymptomatic to pruritic, yellow-orange plaques or nodules that tend to ulcerate and are usually located in the periorbital area, trunk and/or extremities. Strong association with paraproteinemia and/or malignant lymphoproliferative disease has been reported.
Necrotizing enterocolitis (ORPHA:391673)
A rare intestinal disease characterized by potentially life-threatening inflammatory bowel necrosis predominantly affecting preterm neonates. Patients may present with feeding intolerance, lethargy, temperature instability, abdominal distention, blood-stained stools, diarrhea, bilious vomiting, apnea, and signs of sepsis. Radiographic features include pneumatosis intestinalis, portal venous gas, presence of fixed, dilated intestinal loops, bowel wall edema, and (in case of bowel perforation) pneumoperitoneum.
Necrotizing soft tissue infection (ORPHA:440368)
A rare infectious disease characterized by painful, rapidly progressive infection of deep soft tissue structures. Infections can be mono- or polymicrobial and involve gram-positive cocci, enteric gram-negative bacilli, anaerobes, among others. Fungal infections have also been described in rare cases. Physical examination findings are often subtle and may include erythema, bullae, induration of subcutaneous tissues, and tenderness to palpation.
NEK9-related lethal skeletal dysplasia (ORPHA:464366)
NEK9-related lethal skeletal dysplasia is a rare, lethal, primary bone dysplasia characterized by fetal akinesia, multiple contractures, shortening of all long bones, short, broad ribs, narrow chest and thorax, pulmonary hypoplasia and a protruding abdomen. Short bowed femurs may also be associated.
Nelson syndrome (ORPHA:199244)
A rare, acquired, endocrine disease characterized by the triad of diffuse skin and mucosa hyperpigmentation, markedly elevated serum adrenocorticotropin (ACTH) levels and an enlarging corticotroph adenoma, which manifest following total bilateral adrenalectomy performed for the treatment of Cushing's disease. Additionally, patients may present with headaches, visual field defects, cranial nerve palsy, pituitary apoplexy, diabetes insipidus, panhypopituitarism, and, occasionally, paraovarian or paratesticular tumors.
Neonatal acute respiratory distress due to SP-B deficiency (ORPHA:217563)
A rare genetic interstitial lung disease characterized by progressive, life-threatening, refractory respiratory distress in full-term neonates associated with surfactant protein B deficiency. In most cases, the disease is fatal within the first months of life. Lung biopsy reveals changes characteristic of pulmonary alveolar proteinosis with interstitial fibrosis and inflammation, as well as accumulation of lipid-rich, eosinophilic, proteinaceous, granular material consisting of desquamated type II pneumocytes and foamy macrophages within the alveolar air spaces.
Neonatal alloimmune neutropenia (ORPHA:464370)
A rare acquired neutropenia characterized by isolated neutropenia in a newborn due to maternal alloimmunization against human neutrophil antigens (HNA) inherited from the father and present on fetal neutrophils, and subsequent increased breakdown of the latter. The condition is self-limiting and resolves after several weeks. It usually presents with only mild bacterial infections or may even be asymptomatic, although severe forms with sepsis and fatal outcome have also been reported.
Neonatal antiphospholipid syndrome (ORPHA:398097)
Neonatal antiphospholipid syndrome is a rare, secondary, neonatal autoimmune disease characterized by single or recurrent episodes of venous, arterial or mixed thrombosis in a neonate whose mother does not have antiphospholipid syndrome manifestations. Patients present positive antiphospholipid antibodies and may have additional abnormalities associated (e.g. cardiac valve disease, livedo reticularis, thrombocytopenia, nephropathy, neurological manifestations).