TaoMedAI/RareMedData huggingface dataset:
Infantile osteopetrosis with neuroaxonal dysplasia (ORPHA:85179)
This syndrome is characterized by osteopetrosis, agenesis of the corpus callosum, cerebral atrophy and a small hippocampus.
Epidemiology
It has been described in a brother and a sister born to nonconsanguineous Caucasian parents.
Clinical description
The children died at the ages of 1 and 9 months, respectively. Several additional cases combining axonal dystrophy and osteopetrosis have been described.
Etiology
The etiology remains unclear.
Genetic counseling
Autosomal recessive inheritance has been suggested.

                            Last update: 
                            March 2009
Infantile spasms-broad thumbs syndrome (ORPHA:3173)
Infantile spasms-broad thumbs syndrome is a rare neurologic disorder characterized by profound developmental delay, facial dysmorphism (i.e. microcephaly, large anterior fontanel, hypertelorism, downslanting palpebral fissures, beaked nose, micrognathia), broad thumbs and flexion and/or extension spasms. Bilateral cataracts, hypertrophic cardiomyopathy and hydrocele have also been reported. EEG shows hypsarrhythmic features and MRI may reveal partial agenesis of the corpus callosum, mild brain atrophy and/or ventriculomegaly. There have been no further descriptions in the literature since 1990.
Infantile spasms-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome (ORPHA:263410)
A rare, genetic disorder of thiamine metabolism and transport characterized by infantile spasms progressing to symptomatic generalized or partial seizures, severe global developmental delay, progressive brain atrophy, and bilateral thalamic and basal ganglia lesions.
Infantile systemic hyalinosis (ORPHA:2176)
Infantile systemic hyalinosis (ISH) is a very rare disorder belonging to the heterogeneous group of genetic fibromatoses and is characterized by progressive joint contractures, skin abnormalities, severe chronic pain and widespread deposition of hyaline material in many tissues such as the skin, skeletal muscle, cardiac muscle, gastrointestinal tract, lymph nodes, spleen, thyroid, and adrenal glands.
Epidemiology
Less than 20 cases have been described in the literature so far.
Clinical description
The clinical features are evident either at birth or within the first six months of life. Intrauterine growth retardation and reduced fetal movements have been described in some ISH patients. The main clinical features are painful swollen joint contractures, significant discomfort on handling and reduction of spontaneous movement. Dermal abnormalities include diminished skin elasticity, generalized skin thickening with hyperpigmentation over prominences, small pearly papules (predominantly on the face, scalp, and neck), massive gingival hypertrophy, and fleshy nodules in the perianal region. Susceptibility to infections and intractable diarrhea are common findings. Failure to thrive is characteristic. Osteopenia is often present and results in increased susceptibility to bone fractures. Children with ISH are intellectually normal.
Etiology
ISH is caused by mutations in anthrax toxin receptor 2 gene (ANTRX2) on chromosome 4q21. Mutations in the same gene cause juvenile hyaline fibromatosis, a similar but milder disease (see this term).
Diagnostic methods
Diagnosis is clinical and can be further supported by histological evidence of deposition of amorphous hyaline material in the skin or mucosae.
Differential diagnosis
Juvenile hyaline fibromatosis, Winchester syndrome, lipoid proteinosis (Urbach-Wiethe disease) and mucopolysaccharidosis type II (Hunter's syndrome) should be considered in the differential diagnosis (see these terms).
Genetic counseling
ISH is transmitted as an autosomal recessive trait.
Management and treatment
There is no specific treatment for ISH. Physical therapy and nutritional support improve the quality of life of the patients.
Prognosis
ISH has a progressive course that may lead to death within the first two years of life, mostly due to recurrent respiratory infections and severe diarrhea. In patients that live until adulthood, mobility remains severely restricted by joint contractures.

                            Last update: 
                            June 2008


                            - Expert reviewer(s): 
                            Dr Luciano MERLINI
Infantile-onset ascending hereditary spastic paralysis (ORPHA:293168)
Infantile-onset ascending hereditary spastic paralysis (IAHSP) is a very rare motor neuron disease characterized by severe spasticity of the lower limbs in early life, progression of spasticity to the upper limbs in late childhood, and dysarthria.
Epidemiology
The prevalence and incidence of IAHSP are not known. 17 families accounting for at least 30 cases have been reported to date. The disorder has been described in various ethnic groups.
Clinical description
Affected patients are normal at birth and early development is mostly unremarkable. They then develop spastic paraplegia, increased reflexes and sustained lower limb stiffness in the first two years of life. By 7 to 8 years of age they also develop progressive weakness and spasticity extending to the upper limbs. Other signs include dysarthria, dysphagia (sometimes with drooling), and slow eye movements. Most become wheel-chair bound by late childhood or early adolescence and some patients have feeding difficulties (swallowing liquids) starting in the second decade. Subsequently, the disease progresses to severe spastic tetraparesis and a pseudobulbar syndrome may be observed. Cognitive function is generally preserved.
Etiology
IAHSP appears to be caused by mutations in the ALS2 gene (2q33-q35) encoding alsin, a protein that is abundant in motor neurons. Mutations in this gene are not found in all families with members affected by the disease. Other genes or loci have not been identified to date.
Diagnostic methods
Diagnosis is based on the characteristic features of the disorder and on ascending progression. Electrophysiological studies show severe dysfunction of motor evoked potentials. Somatosensory evoked potentials, electromyography and nerve conduction velocities are normal. Magnetic resonance imaging (MRI) is normal in affected children but brain changes are found in older patients. The diagnosis can be confirmed by molecular genetic testing.
Differential diagnosis
Differential diagnoses include the allelic disorders juvenile primary lateral sclerosis and juvenile amyotrophic lateral sclerosis (see these terms).
Antenatal diagnosis
Prenatal diagnosis for at-risk pregnancies is possible if the disease-causing mutations have been identified in the family.
Genetic counseling
IAHSP is inherited in an autosomal recessive manner. The parents of an affected individual are obligate heterozygotes and are therefore asymptomatic carriers. Genetic counseling should be provided to affected families.
Management and treatment
There is currently no specific treatment. Management primarily involves physical and occupational therapy to promote mobility and independence.
Prognosis
The vital prognosis is good with long-term survival in most cases. Quality of life, however, is affected by progressive neurological manifestations and loss of independence.

                            Last update: 
                            February 2014


                            - Expert reviewer(s): 
                            Pr Enrico BERTINI
Infantile-onset autosomal recessive nonprogressive cerebellar ataxia (ORPHA:284332)
A rare, genetic, autosomal recessive cerebellar ataxia disease characterized by nonprogressive cerebellar ataxia, with onset in infancy, manifesting with delayed motor and speech development, gait ataxia, dysmetria, hypotonia, increased deep tendon reflexes, and dysarthria. Additional variable manifestations include moderate nystagmus on lateral gaze, mild spasticity, intention tremor, short stature and pes planus. Brain imaging reveals cerebellar vermis atrophy.
Infantile-onset axonal motor and sensory neuropathy-optic atrophy-neurodegenerative syndrome (ORPHA:457205)
A rare neurologic disease characterized by axonal sensorimotor neuropathy, progressive optic atrophy, cognitive deficit, bulbar dysfunction, seizures, and early hypotonia and feeding difficulties. Additional possible features include dystonia, scoliosis, joint contractures, ocular anomalies, and urogenital anomalies. Brain MRI reveals variable degrees of cerebral atrophy. The disease is fatal in childhood due to respiratory failure.
Infantile-onset generalized dyskinesia with orofacial involvement (ORPHA:494526)
A rare hyperkinetic movement disorder characterized by delayed motor development and infantile onset of axial hypotonia and a generalized hyperkinetic movement disorder, principally with dyskinesia of the limbs and trunk, and facial involvement including orolingual dyskinesia, drooling, and dysarthria. Variable hyperkinetic movements may include a jerky quality, intermittent chorea and ballismus. Brain imaging is normal and cognitive performance is typically preserved.
Infantile-onset mesial temporal lobe epilepsy with severe cognitive regression (ORPHA:391316)
Infantile-onset mesial temporal lobe epilepsy with severe cognitive regression is a rare monogenic disease with infantile-onset pharmacoresistant focal seizures of mesial temporal lobe onset manifesting with unresponsiveness, hypertonia and automatisms and cognitive regression soon after seizure onset leading to severe intellectual disability with behavioral abnormalities.
Infantile-onset periodic fever-panniculitis-dermatosis syndrome (ORPHA:500062)
A rare genetic autoinflammatory syndrome characterized by early-onset of repeated episodes of fever, nodular neutrophil-rich panniculitis, arthralgia, and lipodystrophy. Additional reported features include diarrhea, failure to thrive, lymphadenopathy, and vasculitis. Laboratory examination may reveal elevated serum C-reactive protein and leukocytosis with neutrophilia in the absence of infection.
Infantile-onset pulmonary alveolar proteinosis-hypogammaglobulinemia (ORPHA:572428)
A rare genetic respiratory disease characterized by infantile onset of pulmonary alveolar proteinosis with hypogammaglobulinemia. Patients have normal respiratory function at birth, but subsequently develop recurrent, mainly viral, infections and progressive respiratory failure, often leading to death in infancy or early childhood. Additional reported features include leukocytosis and splenomegaly.
Infantile-onset X-linked spinal muscular atrophy (ORPHA:1145)
A rare form of spinal muscular atrophy characterized by the neonatal onset of severe hypotonia, areflexia, profound weakness, multiple congenital contractures, facial dysmorphic features (myopathic face with open, tent-shaped mouth), cryptorchidism, and mild skeletal abnormalities (i.e. kyphosis, scoliosis), that is often preceded by polyhydramnios and reduced fetal movements in utero and followed by bone fractures shortly after birth. Muscle weakness is progressive and chest muscle involvement eventually leads to ventilatory insufficiency and respiratory failure.
Infection-related hemolytic uremic syndrome (ORPHA:544482)
A rare type of hemolytic uremic syndrome (HUS) characterized by the triad of hemolytic anemia due to generalized thrombotic microangiopathy, thrombocytopenia, and acute kidney injury, and most commonly occurring after acute gastroenteritis due to Shiga toxin-producing enterohemorrhagic Escherichia coli or Shigella dysenteriae. Other infectious causes of HUS include Streptococcus pneumoniae, HIV, Mycoplasma pneumoniae, Histoplasmosis, and Coxsackie virus.
Infectious anterior uveitis (ORPHA:279922)
A rare ophthalmic disorder characterized by inflammation primarily of the anterior part of the uvea (iris and ciliary body), due to an infectious etiology. Clinical symptoms are pain, redness, photophobia, and variable visual loss. Signs on examination include presence of inflammatory cells in the anterior chamber and anterior vitreous, keratic precipitates, hypopyon, iris nodules, posterior synechiae, and miosis, among others.
Infectious epithelial keratitis (ORPHA:137593)
Infectious epithelial keratitis is a rare, potentially sight-threatening, acquired ocular disease chracterized by corneal epithelium inflammation resulting from viral (mainly Herpes Simplex virus), bacterial, fungic or protist infection, manifesting with variable symptoms, such as conjunctival hyperemia, lacrimation, rapid onset of pain, blurred vision and/or photophobia, depending on the causative agent.
Infectious panuveitis (ORPHA:279925)
A rare ophthalmic disorder characterized by generalized inflammation of all parts of the uveal tract (iris, ciliary body, and choroid), simultaneously involving adjacent vitreous and retina, without any predominant site of inflammation, due to viral, bacterial, fungal, or parasitic infections. Clinical symptoms include pain, photophobia, redness, blurring of vision, and floaters. Signs on examination are lid edema, ciliary injection, chemosis, keratic precipitates, cells in the anterior chamber, hypopyon, iris nodules and neovascularization, posterior synechiae, macular edema, vitreous and retinal hemorrhage, and retinal detachment, among others. Complications may result in visual loss.
Infectious posterior uveitis (ORPHA:279919)
A rare ophthalmic disorder characterized by inflammation of the posterior uveal tract (retina and choroid), due to an infectious etiology. Presenting symptoms are decreased visual acuity, visual field defects, floaters, photopsia, photophobia, and occasionally pain. Signs on examination include conjunctival injection, keratic precipitates, retrolental cells, inflammatory infiltrates on the retina, macular edema, and peripheral retinal neovascularization, among others. Complications (such as cataracts, band keratopathy, glaucoma, cystoid macula edema, and retinal detachment) may lead to permanent vision loss.
Infective dermatitis associated with HTLV-1 (ORPHA:289347)
Infective dermatitis associated with HTLV-1 is a rare and severe chronic disease characterized by recurrent chronic eczema (with erythematous, scaly and crusted lesions) mainly affecting seborrheic areas (e.g. scalp, forehead, eyelids, paranasal and periauricular skin, neck, axillae, and groin), a generalized fine papular rash, chronic nasal discharge with crusting of the anterior nares, and non-virulent Staphylococcus aureus or beta-hemolytic Streptococcus infections, thought to be a result of HTLV-1-induced immunosuppression. Lymphadenopathy, anemia, mild to moderate pruritus and increased incidence of other infections (e.g. crusted scabies) have also been reported in some patients. Patients may subsequently develop other HTLV-1 associated conditions such as adult T-cell leukemia/lymphoma and tropical spastic paraparesis (see these terms).
Infective endocarditis (ORPHA:570762)
A rare bacterial infectious disease characterized by infection of a native or prosthetic heart valve, the endocardial surface, or an indwelling cardiac device. Main causative agents are Gram-positive bacteria, most commonly Staphylococcus and Streptococcus species. Signs and symptoms include high fever or prolonged subfebrile state, excessive sweating, malaise, asthenia, arthralgia, myalgia, weight loss, headache, nausea, dyspnea, cough, heart murmurs, and petechiae of the skin. The most common complications are embolism in different organs and ischemic stroke, sepsis, heart failure, and renal failure.
Inferior vena cava interruption without azygos continuation (ORPHA:99123)
A rare congenital anomaly of the inferior vena cava characterized by complete interruption of the vessel in which no direct continuity exists between the inferior vena cava and the azygos/hemiazygos system. Clinical manifestations depend on the variant drainage patterns or collaterals and include lower extremity deep vein thrombosis, thromboembolic attacks, leg swelling and pain, lower extremity varices, abdominal pain, intraabdominal varices, and hematochezia, among others. Additional venous abnormalities or cardiac malformations are frequently present.
Inflammatory bowel disease-recurrent sinopulmonary infections syndrome (ORPHA:529980)
A rare genetic immune disease characterized by recurrent sinopulmonary infections and autoimmune enterocolopathy, manifesting as frequent episodes of intractable diarrhea with abdominal pain and fever, accompanied by eczematous rashes, due to deficits in components of innate and adaptive immunity. Immunologic abnormalities include IgG subclass deficiency, impaired antigen-induced lymphocyte proliferation, reduced cytokine production by CD8+ T lymphocytes, and decreased numbers of natural killer cells.
Inflammatory myofibroblastic tumor (ORPHA:178342)
Inflammatory myofibroblastic tumor is a rare neoplastic lesion of the submucosal stroma, which can develop in any organ, often occurring in the lung, mesentery, omentum and the retroperitoneal region. It is histologically heterogenous, composed of spindle-shaped cells, myofibroblasts and inflammatory cells. It is usually benign, however local invasion, recurrence, malignant transformation with vascular invasion and metastases may occur. The presentation is nonspecific and depends on the organ involved. Some patients may present with paraneoplastic syndrome (fever, malaise, weight loss, anemia, thrombocytosis) or symptoms related to compression of adjacent organs, such as bowel obstruction.
Inflammatory myopathy with abundant macrophages (ORPHA:247718)
A rare idiopathic inflammatory myopathy characterized by diffuse destructive infiltration of CD68+ macrophages into the fascia rather than muscle fibers in muscle biopsies, proximal muscle weakness and myalgia with or without scaly dermatomyositis-like or atypical non-dermatomyositis-like skin lesions, elevation of creatine kinase levels and thickening of muscle fascia in muscle MRI.
Inflammatory pseudotumor of the liver (ORPHA:90003)
A rare benign liver tumor characterized by a prominent inflammatory infiltrate and often mimicking a malignant liver neoplasm. The tumor is frequently solitary with a predilection for the right lobe; however, multiple lesions are possible. There are two clinicopathological subtypes: fibrohistiocytic inflammatory pseudotumor of the liver and lymphoplasmacytic inflammatory pseudotumor of the liver. Patients present with non-specific clinical symptoms such as abdominal pain or discomfort, fever, and weight loss. The condition may be associated with other chronic inflammatory or autoimmune diseases.
Infundibulo-neurohypophysitis (ORPHA:238305)
A type of primary hypophysitis characterized by an inflammation of the posterior pituitary and the stalk. The major clinical manifestation is diabetes insipidus with polyuria and polydipsia. Less frequent symptoms are headaches, adrenal insufficiency, hyperprolactinemia and hypogonadism.
Inhalational anthrax (ORPHA:247257)
Inhalational anthrax is a rare acute systemic infection caused by the inhalation of Bacillus anthracis spores (e.g. through infected animal products, bioterrorism) and characterized by an initial stage where patients present with non specific symptoms (fever, cough, chills, fatigue) that is followed by an acute phase during which hemorrhagic mediastinitis occurs that can progress into meningitis, gastrointestinal involvement, and refractory shock, that can be fatal, if left untreated.
Inhalational botulism (ORPHA:254504)
Inhalational botulism is a man-made form of botulism (see this term), a rare acquired neuromuscular junction disease with descending flaccid paralysis caused by botulinum neurotoxins (BoNTs).
Epidemiology
Prevalence is unknown. So far, nearly 10 cases have been reported worldwide.
Clinical description
Clinical manifestations are similar to other forms of botulism, with symmetrical cranial nerve palsies followed by descending, symmetric flaccid paralysis of voluntary muscles, which may progress to respiratory compromise and death.
Etiology
The disease results from accidental or intentional release of aerosolized BoNTs. After inhalation, the toxin is absorbed into the blood stream and distributed throughout the body, causing the typical manifestations of botulism. The time to onset of inhalational botulism cannot be stated with certainty as few cases are known or because of repeated exposure. Accidental cases were initially reported in three laboratory workers and more recently in illicit drug users after intranasal use of cocaine, through sinusitis and possible sinus colonization and toxicogenesis, or through direct absorption by the nasal mucosa of preformed toxin in contaminated street cocaine. Deliberate dissemination of BoNTs by aerosol could produce an outbreak of inhalational botulism in a large number of simultaneous cases with a common geographic factor, but without common dietary exposure and, possibly, with an unusual BoNT type (e.g. type C, D, F, G). All cases of botulism should be reported to the appropriate government agency.

                            Last update: 
                            April 2011


                            - Expert reviewer(s): 
                            Dr Michel POPOFF
Inherited acute myeloid leukemia (ORPHA:319465)
Inherited acute myeloid leukemia (AML) is a rare, malignant hematopologic disease characterized by clonal proliferation of myeloid blasts, primarily involving the bone marrow, in association with congenital disorders (e.g. Fanconi anemia, dyskeratosis congenita, Bloom syndrome, Down syndrome, congenital neutropenia, neurofibromatosis, etc.) and genetic defects predisposing to AML. Patients present with signs and symptoms related to ineffective hematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement (gingivitis, splenomegaly, etc.). Depending on the underlying genetic defect, there may be additional cancer risks and other health problems present.
Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations (ORPHA:319462)
Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations is a rare cancer-predisposing syndrome, associated with the D1 subgroup of Fanconi anemia (FA), characterized by progressive bone marrow failure, cardiac, brain, intestinal or skeletal abnormalities and predisposition to various malignancies. Bone marrow suppression and the incidence of developmental abnormalities are less frequent than in other FA, but cancer risk is very high with the spectrum of childhood cancers including Wilms tumor, brain tumor (often medulloblastoma) and ALL/AML.
Inherited congenital spastic tetraplegia (ORPHA:210141)
Inherited congenital spastic tetraplegia is a rare, genetic, neurological disease characterized by non-progressive, variable spastic quadriparesis in multiple members of a family, in the absence of additional factors complicating pregnancy or birth (e.g. perinatal asphyxia, congenital infection). Additional clinical features include congenital hypotonia, intellectual disability, and developmental delay. Dysphagia, dysarthria, exotropia, nystagmus, seizures and brain atrophy with ventriculomegaly may be also present.
Inherited Creutzfeldt-Jakob disease (ORPHA:282166)
A rare form of genetic prion disease characterized by typical CJD features (rapidly progressive dementia, personality/behavioral changes, psychiatric disorders, myoclonus, and ataxia) with a genetic cause and sometimes a family history of dementia.