TaoMedAI/RareMedData huggingface dataset:
Primary cutaneous lymphoma (ORPHA:542)
Cutaneous lymphoma is a heterogeneous entity with respect to its clinical and pathological features, evolutive profile, prognosis, molecular aetiology and response to therapy. These specifications have been taken into account in recent classifications, which have placed particular importance on the prognostic implications of these different entities.
Clinical description
Cutaneous T-cell lymphomas can be subdivided into forms with a good prognosis (Mycosis fungoides and CD30+ cutaneous T-cell lymphoma), forms with a poor prognosis (Sezary syndrome and peripheral T-cell lymphoma) and forms with a variable prognosis (pleomorphic small/medium-sized T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, cutaneous T/NK cell lymphomas (referred to as nasal-type lesions), epidermotropic CD8+ T-cell lymphomas and the TCRgamma-delta phenotype). The group of cutaneous B-cell lymphomas includes marginal zone B-cell lymphomas and primary cutaneous follicular lymphomas (both of which have a good prognosis), cutaneous large B-cell lymphomas of the leg (with a variable prognosis), and blastic NK lymphomas (associated with a poor prognosis).
Management and treatment
While treatment is effective and the prognosis is favourable for low grade forms, recent therapeutic innovations relying on the use of biological tools are likely to improve the prognosis for the most severe forms, such as those already existing in the form of anti-CD20 monoclonal antibodies (rituximab) for disseminated cutaneous B-cell lymphomas, and anti-CD52 monoclonal antibody (alemtuzumab) for refractory forms of cutaneous T-cell lymphoma. Deciphering the key molecular mechanisms underlying these malignancies should create new therapeutic perspectives in the close future.

                            Last update: 
                            April 2007


                            - Expert reviewer(s): 
                            Pr Hervé BACHELEZ
Primary cutaneous marginal zone B-cell lymphoma (ORPHA:178536)
A rare, indolent primary cutaneous B-cell lymphoma characterized by multifocal, red to violaceous papules, plaques or nodules localized predominantly on the trunk and extremities. Histologically, these are dermis infiltrates consisting of small, marginal zone B cells, lymphoplasmacytic cells, and plasma cells. Marginal zone B cells express CD20, CD79a and Bcl-2, and are negative for CD5, CD10 and Bcl-6. Plasma cells are typically located at the periphery, and express CD138, CD79a, and monotypic light chains.
Primary cutaneous peripheral T-cell lymphoma not otherwise specified (ORPHA:86885)
An extremely rare, primary cutaneous T-cell lymphoma disorder characterized by solitary, or multifocal and diffuse, cutaneous lesions, ranging from tumor-like patches, plaques, papules, nodules, and/or erythroderma, located on any area of the body, which rapidly progress and may become ulcerated and/or infected. Systemic involvement may be associated.
Primary cutaneous plasmacytosis (ORPHA:451602)
A rare acquired skin disease characterized by benign proliferation of mature plasma cells with a typical triad of cutaneous lesions, polyclonal hypergammaglobulinemia, and superficial lymphadenopathy, without an apparent underlying cause. The skin lesions consist of multiple round-to-oval, red-to-dark-brown macules, papules, and plaques most commonly found on the trunk, but also the face, neck, and axillae.
Primary cutis verticis gyrata (ORPHA:671)
A progressive cutaneous disorder predominantly affecting males, characterized by hypertrophy and thickening of the skin of the scalp, forming convoluted furrows with deep, tender, and cerebriform cutaneous folds. Hair is usually normal in the furrows and sparse on the folds. It can be isolated or associated with other abnormalities, such as intellectual deficit, epilepsy, cataract, blindness, and deafness.
Primary desmosis coli (ORPHA:565641)
A rare intestinal disease characterized by congenital partial or complete lack of the collagen mesh network in the intestinal wall, resulting in hypoperistalsis or aperistalsis. The enteric nervous system is normal or near-normal in the affected areas, although hypo- and dysganglionosis may be found in some proximal segments of the colon and/or small bowel. Patients present with chronic intractable slow transit constipation.
Primary dystonia, DYT13 type (ORPHA:98807)
A rare primary torsion dystonia characterized by focal or segmental dystonia with onset either in the cranial-cervical region or in the upper limbs. Age of onset varies between 5 years and adulthood, with a mean age of onset of 16 years. Clinical manifestations are generally mild and slowly progressive.
Primary dystonia, DYT17 type (ORPHA:370103)
Primary dystonia, DYT17 type is a rare, genetic, isolated dystonia initially presenting as torticollis, and later progressing to segmental or generalized dystonia. Dysphonia and dysarthria also occur later in the disease course.
Primary dystonia, DYT2 type (ORPHA:99657)
A rare isolated dystonia characterized by segmental dystonia that predominantly affects the distal limbs and leads to abnormal posture. This disease has a progressive clinical course and may develop into generalized dystonia but remains mild overall.
Primary dystonia, DYT21 type (ORPHA:306734)
Primary dystonia, DYT21 type is a subtype of mixed dystonia with a late-onset form of pure torsion dystonia.
Primary dystonia, DYT27 type (ORPHA:464440)
A rare genetic dystonia characterized by focal or segmental isolated dystonia involving the face, neck, upper limbs (commonly writing dystonia), larynx, or trunk, with an onset from childhood to early adulthood. Dystonia may be tremulous, giving rise to head or hand tremor. Mode of inheritance is autosomal recessive.
Primary dystonia, DYT4 type (ORPHA:98805)
DYT4 type primary dystonia is characterized by predominantly laryngeal dystonia (manifesting as whispering dysphonia) and cervical dystonia (manifesting as torticollis).
Epidemiology
So far, the disease has been reported in one large Australian family.
Clinical description
The age of onset varies from 13 to 37 years. Some patients develop generalized dystonia and psychiatric symptoms.
Etiology
The locus for DYT4 remains unknown.
Genetic counseling
The disease is transmitted in an autosomal dominant manner.

                            Last update: 
                            April 2009
Primary dystonia, DYT6 type (ORPHA:98806)
A rare genetic movement disorder characterized by dystonia affecting at first an upper limb, less frequently beginning in the head and neck region, before slowly spreading to other locations. The clinical spectrum, like age of onset, is variable with focal, segmental, or generalized distribution, but cranial involvement with speech difficulties and cervical involvement are typical, whereas lower limbs are often spared. With progression of the disease, many patients suffer from generalized dystonia while mostly remaining ambulatory.
Primary essential cutis verticis gyrata (ORPHA:357220)
Primary essential cutis verticis gyrata is a rare, progressive dermis disorder characterized by thickening of the scalp resulting in redundancy of the skin which gives rise to folds and grooves that give the scalp a cerebriform appearance. Folds cannot be corrected by pressure or traction and typically are symmetric and extend anteroposteriorly from vertex to occiput and/or transversely in occipital region. Additional features may include mild subungual hyperkeratosis and distal onycholysis of the nail plates of the great toes. It is not associated with neurological and ophthalmological changes, nor with secondary causes.
Primary failure of tooth eruption (ORPHA:412206)
A rare genetic odontologic disease characterized by failure of eruption of non-ankylosed permanent teeth without evidence of obvious mechanical obstruction. Posterior teeth are preferentially affected (typically with involvement of all teeth distal to the most mesial non-erupted tooth), resulting in a posterior open bite. Non-ankylosed teeth tend to become ankylosed, and orthodontic treatment of affected teeth is generally unsuccessful.
Primary Fanconi renotubular syndrome (ORPHA:3337)
A rare generalized, genetic disorder of proximal tubular transport characterized by excessive urine output with loss of low molecular weight solutes (amino acids, glucose, low-molecular weight proteins, organic acids, carnitine, calcium, phosphate, potassium, bicarbonate) and water, and which can be life threatening.
Epidemiology
The prevalence of the condition is not known.
Clinical description
Onset is typically between infancy and childhood with symptoms related to tubular loss of nutrients, water and electrolytes. Typical clinical features include failure to thrive and rickets, normoglycemic glycosuria and polyuria with bicarbonaturia leading to hyperchloremic metabolic acidosis. Nephrocalcinosis and kidney stones are less common.
Etiology
The genetic etiology has been identified in a handful of families, and includes mutations in either GATM (15q21.1), involved in mitochondrial function, EHHADH (3q27.2), due to a specific mutation (c.7G>A) that introduces a mitochondrial targeting motif, or SLC34A1 (5q35.3) which encodes the proximal tubular sodium-phosphate transporter, NaPi-IIa. However, the disease may be due to unidentified mutations. Of note, the gene SLC34A1 is also associated with two other diseases: autosomal recessive infantile hypercalcemia and dominant hypophosphatemia with nephrolithiasis or osteoporosis.
Diagnostic methods
Diagnosis is based on clinical presentation as well as plasma electrolytes levels and evaluation of urinary solute excretion (aminoaciduria, proteinuria, phosphaturia, calciuria, uricosuria, glycosuria).
Differential diagnosis
Before the diagnosis of primary Fanconi renotubular syndrome is made all causes of secondary Fanconi syndrome must be ruled out, including both inherited (cystinosis, tyrosinemia type I, fructosemia, Wilson's disease, galactosemia, glycogen storage disease, Dent disease, Oculocerebrorenal syndrome of Lowe, arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, mitochondrial cytopathies) and acquired disorders (drug or heavy metal poisoning, malignancies).
Genetic counseling
The majority of reported cases are sporadic and may be associated with de novo mutations. However, hereditary forms have been reported. The pattern of inheritance is autosomal dominant for EHHADH and GATM, and autosomal recessive for SLC34A1. The risk of transmission to offspring is 50% for autosomal dominant disease and, where both parents are heterozygous for the pathogenic mutation, 25% in autosomal recessive disease.
Management and treatment
Treatment is symptomatic. Kidney transplantation is curative.
Prognosis
With adequate fluid, electrolyte and nutrient supplementation, adequate physical and neurocognitive development is usually possible. Mutations in GATM are associated with progressive chronic kidney disease, whereas this has not been observed with EHHADH-associated disease.

                            Last update: 
                            January 2020


                            - Expert reviewer(s): 
                            Pr Detlef BÖCKENHAUER | ERKNet*


                                * European Reference Network
Primary hyperaldosteronism-seizures-neurological abnormalities syndrome (ORPHA:369929)
A rare, genetic, neurologic disease characterized by primary hyperaldosteronism presenting with early-onset, severe hypertension, hypokalemia and neurological manifestations (including seizures, severe hypotonia, spasticity, cerebral palsy and profound developmental delay/intellectual disability).
Primary hypereosinophilic syndrome (ORPHA:314950)
A rare hypereosinophilic syndrome characterized by hypereosinophilia produced by clonal eosinophils derived from neoplastic stem cells in the absence of any secondary cause of eosinophilia and persisting for at least six months. The condition is associated with signs of organ infiltration, dysfunction, and damage. Clinical manifestations are highly variable, depending on the organ systems involved, and include dermatologic, pulmonary, cardiac, gastrointestinal, and cerebral manifestations, among others.
Primary hypergonadotropic hypogonadism-partial alopecia syndrome (ORPHA:2232)
A rare endocrine disorder characterized by primary hypogonadism and partial alopecia. Females present with Mûllerian hypoplasia, absent or streak ovaries, hypoplastic internal genitalia, primary amenorrhea, and sparse or absent axillary and pubic hair. Some patients also presented sparse eyebrows, microcephaly, flat occiput, dorsal kyphosis or mild intellectual disability. The only described male presents with germinal cell aplasia. Affected individual all present partical scalp alopecia.
Primary hypertrophic osteoarthropathy (ORPHA:248095)
Primary hypertrophic osteoarthropathy (PHO) is a genetically and clinically heterogeneous inherited disorder characterized by digital clubbing and osteoarthropathy, with variable features of pachydermia, delayed closure of the fontanels, and congenital heart disease. There are two types of PHO: pachydermoperiostosis and cranio-osteoarthropathy (see these terms).
Epidemiology
Prevalence is unknown. Cranio-osteoarthropathy is the rarest form, with about 30 cases reported to date.
Clinical description
Patients typically present in infancy with clubbing, hyperhidrosis, bone and joint pain and skin thickening. The clinical constellation of PHO includes skin thickening and excessive sweating (pachydermoperiostosis), delayed closure of the cranial sutures (cranio-osteoarthropathy) and congenital heart disease, especially patent arterial duct (see this term).
Etiology
Mutations in the HPGD gene (4q33-q34) encoding 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the main enzyme of prostaglandin degradation, have been identified.
Diagnostic methods
Diagnosis is based on clinical signs and X-ray exam, magnetic resonance imaging (MRI) or radionucleotide bone imaging showing typical bone abnormalities, such as diaphyseal periostosis and acro-osteolysis.
Differential diagnosis
Differential diagnoses include secondary hypertrophic osteoarthropathy, chronic recurrent non-bacterial osteomyelitis, SAPHO and Camurati-Engelman syndromes (see these terms) and chronic bacterial osteomyelitis.
Genetic counseling
PHO is inherited as an autosomal recessive trait; however, heterozygous carriers can have a mild phenotype. Since mutations in the HPGD gene have recently been reported, genetic counseling and prenatal diagnosis might be considered.
Management and treatment
Rheumatological symptoms can be improved by nonsteroidal anti-inflammatory drugs, which have been shown to directly influence the pathogenesis. In addition, corticosteroids or colchicine have been tried. Clinical improvement of the dermatological symptoms is achieved by retinoids. Plastic surgery may be helpful for facial involvement. Finger clubbing surgical reduction has been tried with success.
Prognosis
PHO progresses constantly, leaving patients with chronic debilitating complications, such as clubbing and arthritis.

                            Last update: 
                            January 2011


                            - Expert reviewer(s): 
                            Pr Hermann GIRSCHICK
Primary hypomagnesemia with hypercalciuria and nephrocalcinosis with severe ocular involvement (ORPHA:2196)
Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis with severe ocular involvement (FHHNCOI) is a form of familial primary hypomagnesemia (FPH, see this term), characterized by excessive magnesium and calcium renal wasting, bilateral nephrocalcinosis, progressive renal failure and severe ocular abnormalities.
Epidemiology
To date, approximately 72 cases have been described in the literature.
Clinical description
FHHNCOI has a childhood onset. The initial symptoms may include recurrent urinary tract infections, polyuria and polydipsia. Additional features include nephrocalcinosis, nephrolithiasis, enuresis, abdominal pain, muscular twitches and failure to thrive. The clinical hallmark of this disorder is an ocular abnormality involving severe bilateral myopia with divergent squint, nystagmus, keratoconus, corneal calcifications, cataract, chorioretinitis, pigmentary retinitis, pigmentary maculopathy, macular coloboma, strabismus or visual loss. Renal function generally declines progressively in most patients and patients may reach end stage renal disease in their adolescence or young adulthood. 50% of patients require renal replacement therapy in the second decade of life.
Etiology
FHHNCOI is caused by mutations in CLDN19 (1p34.2) which encodes claudin-19, a protein member of the claudin family which is highly expressed in the tight junctions of the thick ascending limb of Henle's loop, as well as in the retinal epithelium.
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child.

                            Last update: 
                            February 2014


                            - Expert reviewer(s): 
                            Dr Rosa VARGAS-POUSSOU
Primary hypomagnesemia with hypercalciuria and nephrocalcinosis without severe ocular involvement (ORPHA:31043)
Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis without severe ocular involvement (FHHN) is a form of familial primary hypomagnesemia (FPH; see this term), characterized by recurrent urinary tract infections, nephrolithiasis, bilateral nephrocalcinosis, renal magnesium (Mg) wasting, hypercalciuria and kidney failure.
Epidemiology
To date, more than 110 individuals have been reported in the literature.
Clinical description
FHHN has an onset in childhood and the clinical manifestations are recurrent urinary tract infections, polyuria, polydipsia, enuresis, hematuria, nephrolithiasis and bilateral nephrocalcinosis. Some patients fail to thrive during early childhood and experience seizures, vomiting, abdominal pain, tetany and rarely rickets. Ocular involvement is rare and when observed it is relatively mild (myopia, hypermetropia, astigmatism and strabism). Approximately one third of patients progress to renal failure or end-stage renal disease (ESRD) during adolescence.
Etiology
FHHN is characterized by impaired tubular reabsorption of Mg and calcium (Ca) in the thick ascending limb of Henle's loop due to mutations in CLDN16 (3q27), which encodes claudin-16 (previously known as paracellin 1). A significant residual function is observed in several missense mutations, whereas a complete loss of claudin-16 function appears to be more severe (disease presenting earlier and often progressing to kidney failure at a significantly younger age).
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child.

                            Last update: 
                            February 2014


                            - Expert reviewer(s): 
                            Dr Rosa VARGAS-POUSSOU
Primary hypomagnesemia-refractory seizures-intellectual disability syndrome (ORPHA:564178)
A rare genetic disorder of magnesium transport characterized by infantile onset of generalized seizures and severe hypomagnesemia due to massive renal magnesium wasting. Seizures persist despite magnesium supplementation and are associated with significant global developmental delay and intellectual disability. Brain MRI may show reduced cerebral volume.
Primary immunodeficiency syndrome due to P14/LAMTOR2 deficiency (ORPHA:90023)
Primary immunodeficiency syndrome due to p14 deficiency is characterised by short stature, hypopigmentation, coarse facies and frequent bronchopulmonary Streptococcus pneumoniae infections.
Epidemiology
To date, it has been described in four members of one family.
Etiology
Linkage analysis led to the identification of a homozygous deletion in the coding region of the ROBLD3 gene, resulting in reduced expression of the endosomal adaptor protein p14.

                            Last update: 
                            March 2007
Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency (ORPHA:75391)
A rare DNA repair defect other than combined T-cell and B-cell immunodeficiencies characterized by intrauterine and postnatal growth retardation resulting in short stature, microcephaly, glucocorticoid deficiency, natural killer cell deficiency, and recurrent viral infections. Patients may also have increased susceptibility to cancer.
Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection (ORPHA:431166)
Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection is a rare primary immunodeficiency due to a defect in innate immunity disorder characterized by selective susceptibility to viral infections, particularly after systemic challenge with live viral vaccines, such as the measles, mumps and rubella (MMR) vaccine. Patients present severe, potentially fatal, manifestations to viral illness, including encephalitis, hepatitis and pneumonitis.
Primary interstitial lung disease specific to childhood due to pulmonary surfactant protein anomalies (ORPHA:100049)
A group of interstitial lung diseases (ILD) induced by genetic mutations disrupting surfactant function and gas exchange in the lung. The disorders caused by these mutations affect full-term infants and older children and exhibit considerable overlap in their clinical and histologic presentation.
Primary intrahepatic lithiasis (ORPHA:480506)
A rare biliary tract disease characterized by stone formation within the intrahepatic bile ducts without any known cause, leading to bile stasis and repeated cholangitic episodes. The condition is rare in the Western world but frequent in eastern Asia. Patients usually present before the age of forty with right upper quadrant pain, jaundice, and/or fever. Stones are typically calcium bilirubinate (pigment) stones, and bacteria are present in the bile in almost all cases. Complications are biliary strictures, liver abscess, liver fibrosis, and secondary biliary cirrhosis. Association with cholangiocarcinoma has also been reported.
Primary intraosseous venous malformation (ORPHA:140436)
Primary intraosseous venous malformation is a rare, genetic vascular anomaly characterized by severe blood vessel expansion (most frequently within the craniofacial bones) with painless bone enlargement (usually of mandibule, maxilla and/or orbital, nasal, and frontal bones), typically resulting in facial asymmetry and contour deformation. Midline abnormalities, such as diastasis recti, supraumbilical raphe, and hiatus hernia, are commonly associated. Additional features reported include gingival bleeding, ectopic tooth eruption, exophthalmos, loss of vision, nausea, and vomiting.
Primary laryngeal lymphangioma (ORPHA:137926)
Primary laryngeal lymphangioma is a rare, benign, congenital malformation of the lymphatic system characterized by a polypoidal, variable-sized, soft tissue mass located in the larynx. Most lesions manifest by the 2nd year of life and, depending on the size, patients may present with changes in voice, dysphagia, stridor, airway obstruction and/or respiratory distress. Cystic hygroma of the neck is frequently associated.
Primary lateral sclerosis (ORPHA:35689)
Primary lateral sclerosis (PLS) is an idiopathic non-familial motor neuron disease characterized by slowly progressive upper motor neuron dysfunction leading to spasticity, mild weakness in voluntary muscle movement, hyperreflexia, and loss of motor speech production.