TaoMedAI/RareMedData huggingface dataset:
Drug-induced autoimmune hemolytic anemia (ORPHA:90037)
Drug-induced autoimmune hemolytic anemia is a type of autoimmune hemolytic anemia (AIHA; see this term) that occurs as a reaction to therapeutic drugs, and can be due to various mechanisms.
Epidemiology
Drug-induced AIHA is rare; annual incidence is estimated at about 1/1,000,000. It is more common in adults and is very rare in children, although some fatal cases in children have been reported.
Clinical description
The disease presents with anemia linked to hemolysis, and physical examination may show an enlarged spleen.
Etiology
To date about 100 drugs have been implicated in drug-induced AIHA, including: cephalosporins (primarily cefotetan and ceftriaxone), levodopa, methyldopa, penicillin and its derivatives, quinidine and some nonsteroidal anti-inflammatory drugs.
Diagnostic methods
It is important to consider drug-induced AIHA when a patient serologically presents as either warm- or cold-type AIHA (see these terms) to avoid erroneous diagnosis.
Management and treatment
Stopping the drug that is causing the problem may relieve or control the symptoms. Patients may also be given IV immunoglobulin and prednisone to reduce the immune response. Blood transfusion may be needed in severe cases.
Prognosis
The prognosis is good if the causative drug is identified and the patient stops taking it. Death is a rare outcome, but has been reported particularly in children with AIHA caused by cefotetan and ceftriaxone.

                            Last update: 
                            August 2010


                            - Expert reviewer(s): 
                            Pr Marc MICHEL
Drug-induced localized lipodystrophy (ORPHA:90157)
Drug-induced localized lipodystrophy is a rare, acquired, localized lipodystrophy characterized by the appearance of asymptomatic, well-demarcated, variably sized, depressed, lipoatrophic lesions secondary to subcutaneous, intradermic or intramuscular drug injection, including corticosteroids, insulin, human growth hormone and antibiotics. Skin coloration may vary from white or hypopigmented to reddish, pinkish or violaceous. Epidermal atrophy may be also present.
Drug-induced lupus erythematosus (ORPHA:231111)
A rare, systemic disease with skin involvement characterized by the onset of idiopathic lupus erythematosus-like signs and symptoms resulting from continuous drug intake (>1 month), which resolve when treatment is discontinued, in persons with no history of autoimmune disease. Manifestations are variable and may be systemic (e.g. arthralgia, myalgia, fever, fatigue, serositis, pleuritis, pericarditis), subacute cutaneous (incl. photosensitive, non-scarring, annular, polycyclic or papulosquamous lesions, malar erythema, vasculitis, bullous lesions, erythema multiforme-like changes), and/or chronic cutaneous (typically discoid lesions in sun-exposed areas). Procainamide and hydralazine are the drugs most frequently implicated.
Drug-induced vasculitis (ORPHA:251325)
A rare secondary vasculitis characterized by inflammation of blood vessels caused by various drugs, including antibiotics, anti-tumor necrosis factor-alpha agents, immunotherapeutic drugs, and psychoactive agents, among others. The skin is most commonly affected, but other tissues and organs, such as the subcutis, kidneys, or lungs, may also be involved. Systemic disease develops only in a minority of patients, typically when treated with the causative drug over a prolonged period of time. Presenting signs and symptoms include skin rash, myalgia, arthralgia, fever, and malaise.
Epidemiology
The incidence and prevalence of drug-induced vasculitis remains unknown. No population-based study has been performed.
Clinical description
Drug-induced vasculitis typically presents with a petechial rash, purpura and skin necrosis. Symptoms are usually mild and localized. Rarely, systemic involvement of the lungs, kidneys, central nervous system, and/or liver can occur; this can be severe and potentially life-threating. Clinical features include rash, fever, malaise and myalgia, with a temporal relationship with drug administration.
Etiology
The etiology of drug-induced vasculitis (DIV) is incompletely understood, however, aberrant NETosis, breakdown in immune tolerance and epitope spreading, implicated in the development of autoimmunity, have been identified as potential etiological mechanisms.
Diagnostic methods
Drug-induced vasculitis is a diagnosis of exclusion. There is no laboratory diagnostic tool for drug-induced vasculitis. Eosinophil count may be raised; this is seen more frequently in the case of systemic involvement. A comprehensive drug history of prescribed and over-the-counter medicines is paramount. Tissue biopsy can be beneficial in confirming the diagnosis.
Differential diagnosis
Differential diagnosis includes systemic lupus erythematosus, other non-drug-induced ANCA-vasculitis, infections, and malignancies.
Management and treatment
Treatment is focused on stopping administration of the offending agent, and is enough to induce remission in mild cases. In addition, short-course and low-dose steroids therapy can be beneficial. For severe presentations, higher doses of steroids for longer durations may be required. In severe systemic presentations patients can be treated according to ANCA-vasculitis flare protocols. Plasma exchange can also be considered. Relapse is likely upon reintroduction of the offending drug.
Prognosis
Most cases are mild and resolve with cessation of the offending drug without any long-term sequelae. However, in cases with severe systemic involvement, drug-induced vasculitis can result in critical illness and death.

                            Last update: 
                            March 2023


                            - Expert reviewer(s): 
                            Dr Eithne NIC AN RÍOGH
Duane anomaly-myopathy-scoliosis syndrome (ORPHA:50817)
A rare genetic disease characterized by bilateral Duane retraction syndrome type 3 (consisting of severe limitation of abduction, restriction of adduction, retraction of the globe, and narrowing of the palpebral fissure) and congenital myopathy manifesting as mild non-progressive hypotonia without muscular weakness, as well as delayed motor milestones, severe early-onset scoliosis, and short stature. Intelligence is normal.
Duane retraction syndrome with congenital deafness (ORPHA:529574)
A rare neurologic disease characterized by the presence of Duane retraction syndrome (i. e. a congenital cranial dysinnervation disorder with unilateral or bilateral limitation of abduction and/or adduction of the eye, as well as globe retraction and palpebral fissure narrowing on attempted adduction) in combination with congenital unilateral or bilateral hearing loss. The sidedness of hearing loss corresponds to the sidedness of the retraction syndrome.
Duplication of the pituitary gland (ORPHA:314621)
A rare midline cerebral malformation characterized by duplicated pituitary stalks and/or glands within duplicated sella. Patients may present various degrees of facial dysmorphism and endocrine abnormalities, including precocious puberty, hypogonadism, hypothyroidism and/or hyperprolactinemia, as well as associated congenital anomalies, such as clift lip/palate, bifid nasal bridge/tongue/uvula, hypothalamic enlargement with or without hamartoma, nasopharyngeal tumors, corpus callosum agenesis/hypoplasia, basilar artery duplication, and/or vertebral defects (in particular, duplication of the odontoid process).
Duplication of urethra (ORPHA:237)
A rare congenital genitourinary anomaly, encompassing a wide spectrum of anatomic variants in which the urethra is partially or totally duplicated, which may be asymptomatic or cause symptoms such as incontinence, recurrent urinary infections and difficulty urinating.
Dural sinus malformation (ORPHA:97339)
A rare neurovascular malformation characterized by massive dilation of one or more dural sinuses typically associated with arteriovenous shunts. Anatomic types are the lateral type involving the jugular bulb, which presents with minimal symptoms, and the usually symptomatic midline type involving the confluens sinuum (torcular Herophili) and adjacent posterior sinuses. Complications include sinus thrombosis, venous infarction, and cerebral hemorrhage, as well as cardiac failure, macrocrania, and hydrocephalus. Spontaneous regression of the malformation may occur.
DYRK1A-related intellectual disability syndrome due to 21q22.13q22.2 microdeletion (ORPHA:268261)
A rare, syndromic intellectual disability characterized by global developmental delay including severely delayed or absent speech, moderate to severe intellectual disability, behavioral issues, stereotypic behavior, febrile seizures and epilepsy, abnormal gait, vision defects, and characteristic facial features. Intrauterine growth restriction and feeding difficulties are frequently present.
Dyschromatosis symmetrica hereditaria (ORPHA:41)
A rare genodermatosis characterized by the presence of the mixture of hyperpigmented and hypopigmented macules of approximately 5mm in diameter, principally located on the extremities.
Epidemiology
DSH has been reported mainly in eastern Asia including Japan, although genetically confirmed DSH cases have also been reported in Thai, Indian, European, and Hispanic populations. The prevalence of DSH in Japan is estimated to be approximately 1/67,000 people. There does not appear to be male or female predominance. Pathogenic ADAR was also observed in the American population based on a genetic mutation database which implies that DSH patients might be found in the United States.
Clinical description
The first manifestations of the disease generally appear during early childhood and 70% of patients show eruptions until the age of 7. The eruptions might be exacerbated until the age of 20. Skin manifestations on the hands of DSH patients tend to worsen in summer. Quantitative analysis of seasonal changes in DSH severity revealed that sun exposure is only a transiently aggravating factor.
Etiology
The disease is caused by monoallelic mutations in double-stranded RNA-specific adenosine deaminase 1 (ADAR1) gene. Biallelic ADAR1 mutations may also cause a form of Aicardi-Goutières syndrome (a severe genetic inflammatory disease in childhood that affects the brain and the skin, and mimics viral infection) or bilateral striatal necrosis (affecting the central nervous system).
Diagnostic methods
Diagnosis is suspected on clinical presentation and confirmed by genetic testing. Although DSH shows autosomal dominant inheritance with nearly complete penetrance, intrafamilial variation of severity of skin manifestation can be seen. Thus, ultraviolet light examination can be useful to check the slight skin manifestation.
Differential diagnosis
The differential diagnosis includes xeroderma pigmentosum, dyschromatosis universalis hereditaria, reticulate acropigmentation of Kitamura and Aicardi-Goutières syndrome caused by ADAR1 mutations.
Antenatal diagnosis
Prenatal diagnosis is possible where the pathogenic variant has previously been identified in a family member.
Genetic counseling
The disorder is autosomal dominant; some cases occur sporadically. Genetic counseling should be offered to affected individuals informing them that there is a 50% risk of having an affected child at each pregnancy. The genetic penetrance is almost 100%.
Management and treatment
There is no curative treatment. Topical sunscreen and sun-protective clothing can help to control the skin lesions.
Prognosis
DSH patient usually have a normal life expectancy.

                            Last update: 
                            June 2023


                            - Expert reviewer(s): 
                            Pr Michihiro KONO
Dyschromatosis universalis hereditaria (ORPHA:241)
A rare, genetic, pigmentation anomaly of the skin characterized by generalized, irregularly shaped, asymptomatic, hyper- and hypopigmented macules distributed in a reticular pattern involving the trunk, limbs, and sometimes the face. The palms, soles and mucosa are usually not affected. Systemic abnormalities have been rarely reported.
Dysembryoplastic neuroepithelial tumor (ORPHA:251946)
A rare mixed neuronal-glial tumor characterized by a benign, usually supratentorial lesion with predominantly cortical location and multinodular architecture. The tumor typically becomes symptomatic in the second or third decade of life with drug-resistant partial seizures. Histological hallmark is the specific glioneuronal element, columns oriented perpendicularly to the cortical surface, formed by bundles of axons attached to oligodendroglia-like cells, while neurons appear to float in an abundant eosinophilic matrix.
Dysequilibrium syndrome (ORPHA:1766)
Dysequilibrium syndrome (DES) is a non-progressive cerebellar disorder characterized by ataxia associated with an intellectual disability, delayed ambulation and cerebellar hypoplasia.
Epidemiology
To date, more than 50 individuals have been reported in the world literature.
Clinical description
DES is a congenital disorder characterized by nonprogressive cerebellar ataxia, associated with a moderate to profound intellectual disability and delayed ambulation. Gait can be either bipedal or quadrupedal. Additional features include hypotonia, lack of coordination, delayed motor development, seizures, dysarthria, strabismus, short stature and pes planus.
Etiology
Etiological subtypes of DES have been reported and include type 1 (CAMRQ1), 2 (CAMRQ2), 3 (CAMRQ3) and 4 (CAMRQ4) which are attributed to mutations in VLDLR (9p24), CA8 (8q12.1), WDR81 (17p13.3) and ATP8A2 (13q12) genes, respectively. VLDLR encodes the very low density lipoprotein receptor (VLDLR) which is involved in neuronal migration in the cerebral cortex and cerebellum. CA8 encodes a carbonic-anhydrase related protein, whose biological function is not yet fully understood. The function of WDR81 is still unknown. ATP8A2 encodes an ATPase which is mainly expressed in brain tissue, with the highest levels found in the cerebellum, and that may be critical for the developmental processes of the central nervous system.
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: 
                            March 2016


                            - Expert reviewer(s): 
                            Pr Kym BOYCOTT
Dysferlin-related limb-girdle muscular dystrophy R2 (ORPHA:268)
A subtype of autosomal recessive limb-girdle muscular dystrophy characterized by an onset in late adolescence or early adulthood of slowly progressive, proximal weakness and atrophy of shoulder and pelvic girdle muscles. Cardiac and respiratory muscles are not involved. Hypertrophy of the calf muscles and highly elevated serum creatine kinase levels are frequently observed.
Dysmorphism-cleft palate-loose skin syndrome (ORPHA:1779)
Dysmorphism-cleft palate-loose skin syndrome is a rare, genetic developmental defect during embryogenesis characterized by severe psychomotor delay, intellectual disability, congenital, symmetrical circumferential skin creases of arms and legs, cleft palate, and facial dysmorphism (incl. elongated face, high forehead, blepharophimosis, short palpebral fissures, microphthalmia, microcornea, epicanthic folds, telecanthus, microtia, posteriorly angulated ears, broad nasal bridge, microstomia and micrognathia). Additional features reported include short stature, microcephaly, hypotonia, pectus excavatum, severe scoliosis, hypoplastic scrotum, and mixed hearing loss.
Dysmorphism-conductive hearing loss-heart defect syndrome (ORPHA:289553)
Dysmorphism-conductive hearing loss-heart defect syndrome is a rare, multiple congenital anomalies syndrome characterized by a distinctive facial appearance (low frontal hairline, bilateral ptosis, prominent eyes, flat midface, broad, ﬂat nares, Cupid's bow upper lip vermilion, and small, low-set, posteriorly rotated ears), in addition to cleft palate, conductive hearing loss, heart defects (atrial or ventricular septal defect) and mild developmental delay/intellectual disability.
Dysmorphism-pectus carinatum-joint laxity syndrome (ORPHA:2104)
Dysmorphism-pectus carinatum-joint laxity syndrome is characterised by joint laxity, pectus carinatum and facial dysmorphism (mild frontal bossing, a beaked nose with a low nasal bridge, malar hypoplasia, chubby cheeks, a striking philtrum and arched upper lips). It has been described in two siblings. The mode of transmission is unknown.
Dysmorphism-short stature-deafness-difference of sex development syndrome (ORPHA:2282)
Dysmorphism-short stature-deafness-disorder of sex development syndrome is characterized by dysmorphism (including facial asymmetry, arched eyebrows, hypertelorism, broad and flat nasal bridge, microtia, small nose with anteverted nostrils, micrognathia), deafness, cleft palate, male pseudohermaphroditism, and growth and psychomotor retardation. It has been described in two siblings. It is transmitted as an autosomal recessive trait.
Dysosteosclerosis (ORPHA:1782)
A rare genetic primary bone dysplasia disease characterized by progressive osteosclerosis and platyspondyly.
Epidemiology
Less than 30 cases of Dysosteosclerosis have been reported in the literature to date.
Clinical description
The disease is characterized by sclerosis of the skull base, ribs, clavicles, scapulae, mid-diaphyses and increased bone fragility. Patients have a prominent forehead, narrow midface, flattening of the vertebral bodies and dental anomalies. Short stature, optic atrophy, hearing impairment, epilepsy, skin changes, and progressive psychomotor deficit are frequent.
Etiology
The disease is caused by mutations in SLC29A3. This gene encodes a nucleoside transporter. Mutations in this gene may also cause Faisalabad histiocytosis, Rosai-Dorfman disease, H syndrome, and pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome. Parental consanguinity has been noted in some cases. Mutations in osteopetrosis genes TNFRSF11A and TCIRG1 can also cause dysosteosclerosis.
Diagnostic methods
Sequencing combined by deletion and duplication analysis is possible.
Differential diagnosis
Osteopetrosis is more common than dysosteosclerosis and distinguishing features are the presence of sclerotic platyspondyly as well as widened and relatively radiolucent sub-metaphyseal regions of long tubular bones with sclerotic diaphysis. Responsible genes include OSTM1, SNX10, CA2, TCIRG1, TNFSF11, CLCN7, PLEKHM1, TNFRSF11A, and LRP5. In Pyle disease, there is important metaphyseal expansion with cortical thinning of the tubular bones well into the diaphyses. There can be mild platyspondyly and skull sclerosis but not as much as in dysosteosclerosis. Genu valgum is a key clinical feature. The responsible gene is SFRP4. In BANDDOS (Brain abnormalities, neurodegeneration, and dysosteosclerosis), there are bone changes similar to dysosteosclerosis, osteopetrosis or Pyle disease, but there is also neurological disease of neonatal, childhood or adult onset. The responsible gene is CSF1R.
Genetic counseling
Dysosteosclerosis is inherited in an autosomal recessive manner for SLC29A3, TNFRSF11A and TCIRG1 mutation. An X-linked pedigree has also been reported.
Management and treatment
Management is mostly supportive, bone marrow transplantation was tried in one individual without success.
Prognosis
The overall prognosis is generally poor, although, as in osteopetrosis, there is a wide spectrum of severity.

                            Last update: 
                            June 2020


                            - Expert reviewer(s): 
                            Dr Philippe CAMPEAU
Dysostosis with brachydactyly (ORPHA:69028)
Brachydactyly ('short digits') is a general term that refers to disproportionately short fingers and toes, and forms part of the group of limb malformations characterized by bone dysostosis.
Epidemiology
The various types of isolated brachydactyly are rare, except for types A3 and D.
Clinical description
Brachydactyly can occur either as an isolated malformation or as part of a complex malformation syndrome. To date, many different forms of brachydactyly have been identified. Some forms also result in short stature. In isolated brachydactyly, subtle changes elsewhere may be present. Brachydactyly may also be accompanied by other hand malformations, such as syndactyly, polydactyly, reduction defects, or symphalangism.
Etiology
For the majority of isolated brachydactylies and some syndromic forms of brachydactyly, the causative gene defect has been identified. In isolated brachydactyly, the inheritance is mostly autosomal dominant with variable expressivity and penetrance.
Diagnostic methods
Diagnosis is clinical, anthropometric and radiological.
Antenatal diagnosis
Prenatal diagnosis is usually not indicated for isolated forms of brachydactyly, but may be appropriate in syndromic forms. Molecular studies of chorionic villus samples at 11 weeks of gestation and by amniocentesis after the 14th week of gestation can provide antenatal diagnosis if the causative mutation in the family is known.
Genetic counseling
The nature of genetic counseling depends both on the pattern of inheritance of the type of brachydactyly present in the family and on the presence or absence of accompanying symptoms.
Management and treatment
There is no specific management or treatment that is applicable to all forms of brachydactyly. Plastic surgery is only indicated if the brachydactyly affects hand function or for cosmetic reasons, but is typically not needed. Physical therapy and ergotherapy may ameliorate hand function.
Prognosis
Prognosis for the brachydactylies is strongly dependent on the nature of the brachydactyly, and may vary from excellent to severely influencing hand function. If brachydactyly forms part of a syndromic entity, prognosis often depends on the nature of the associated anomalies.

                            Last update: 
                            June 2008


                            - Expert reviewer(s): 
                            Dr Mona AGLAN  - Pr Samia TEMTAMY
Dysphagia lusoria (ORPHA:99082)
A rare aortic arch defect characterized by variable degrees of dysphagia due to compression of the esophagus from an aberrant right subclavian artery (arteria lusoria), which arises as the fourth branch, distal to the left subclavian artery, from the aortic arch. In most cases, the aberrant vessel then passes posterior to the esophagus, less frequently between the trachea and esophagus, or anterior to the trachea. Children may also present with stridor and recurrent chest infections.
Dysplasia epiphysealis hemimelica (ORPHA:1822)
A rare bone development disorder characterized by localized, asymmetric osteochondral overgrowth affecting single or multiple epiphyses, most commonly the distal femur, proximal tibia, and talus. The lesions are typically restricted to one side of the epiphysis, with the medial side being affected twice as often as the lateral side. The condition is usually diagnosed in children, and three times more often in boys than in girls. Patients present with pain, limitation in range of motion, and deformity or swelling of the affected joint.