TaoMedAI/RareMedData huggingface dataset:
Tetrasomy X (ORPHA:9)
Tetrasomy X is a sex chromosome anomaly caused by the presence of two extra X chromosomes in females (48,XXXX instead of 46,XX).
Epidemiology
Prevalence is unknown but only around 40 cases have been reported in the literature so far.
Clinical description
Tetrasomy X is associated with delayed speech, learning difficulties, developmental delay and facial dysmorphism. Although disease severity is variable, the learning difficulties and developmental delay are generally mild to moderate. Commonly associated facial features include hypertelorism, upslanting palpebral fissures, epicanthal folds and a flat nasal bridge. Other anomalies may include dental abnormalities, hypotonia and joint laxity, radioulnar synostosis, heart defects, hip dysplasia, and ovarian dysfunction. An increased susceptibility to infections during childhood has also been reported.
Etiology
Tetrasomy X is generally thought to arise as a result of successive maternal nondisjunction during meiosis.

                            Last update: 
                            January 2010


                            - Expert reviewer(s): 
                            Dr Natalie AYARI  - Dr A BERGE  - Dr Susan HOWELL  - Dr Nicole TARTAGLIA
TFR2-related hemochromatosis (ORPHA:225123)
A form of rare hemochromatosis (HC) characterized by excessive tissue iron deposition of genetic origin and presenting with liver disease, hypogonadism, arthritis, diabetes and skin pigmentation.
Epidemiology
Less than 50 cases have been reported in the literature. It is mainly found in Caucasian populations but has also been reported in Asia.
Clinical description
TFR2-related hemochromatosis concerns middle aged-adults but also adolescents and young adults (<30 years old). It resembles symptomatic HFE-related hemochromatosis and presents with liver disease, hypogonadism, arthritis, diabetes and skin pigmentation. Biochemical abnormalities include elevated serum iron, transferrin saturation and ferritin.
Etiology
It is due to mutations of the transferrin receptor 2 gene (TFR2) on chromosome 7. These mutations lead to hypohepcidinemia which in turn causes iron excess through increased intestinal iron absorption and iron release from spleen macrophages.
Diagnostic methods
Diagnosis is based on biochemical testing using serum transferrin saturation and serum ferritin, and on imaging testing for quantifying visceral iron overload (magnetic resonance imaging). Molecular genetic blood testing permits to confirm the diagnosis.
Differential diagnosis
Differential diagnosis includes: a) in younger patients: HJV or HAMP-related hemochromatosis and post-transfusional iron overload in the case of hematological diseases such as thalassemia major, sickle cell disease, and other rare iron-loading anemias b) in older patients: HFE-related hemochromatosis and other adult-onset rare forms of non-HFE-related hemochromatosis (SLC40A1-related HC, for example).
Genetic counseling
Genetic counseling should be offered to first-degree relatives of patients with genetically confirmed TFR2-related hemochromatosis. Particular focus should be given to siblings as they are at the highest risk (25%).
Management and treatment
Patients are treated by repeated phlebotomies that are performed weekly until the ferritin level reaches 50 µg/L, after which they are performed every 1-3 months.
Prognosis
Prognosis can be considered as good, provided that the patients are treated early, before the development of severe visceral complications (especially cirrhosis).

                            Last update: 
                            August 2023


                            - Expert reviewer(s): 
                            Pr Graça PORTO | EuroBloodNet*


                                * European Reference Network
Thakker-Donnai syndrome (ORPHA:1780)
A rare, genetic, lethal, multiple congenital anomalies/dysmorphic syndrome characterized by facial dysmorphism (including long, downward slanting palpebral fissures, hypertelorism, posteriorly rotated ears, broad nasal bridge, short nose with a bulbous tip and anteverted nares, downturned corners of the mouth) as well as vertebral (occult spina bifida, hemivertebrae), brain (ventricular dilatation, agenesis of corpus callosum), cardiac (tetralogy of Fallot, ventricular septal defect) and gastrointestinal (short esophagus with intrathoracic stomach, small intestine, spleen and pancreas, anal atresia) malformations. There have been no further descriptions in the literature since 1991.
Thalidomide embryopathy (ORPHA:3312)
Thalidomide embryopathy is a group of anomalies presented in infants as a result of in utero exposure (between 20-36 days after fertilization) to thalidomide, a sedative used in treatment of a range of conditions, including morning sickness, leprosy and multiple myeloma (see these terms). Thalidomine embryopathy is characterized by phocomelia, amelia, forelimb and hand plate anomalies (absence of humerus and/or forearm, femur and/or lower leg, thumb anomalies). Other anomalies include facial hemangiomas, and damages to ears (anotia, microtia), eyes (microphthalmia, anophthalmos, coloboma, strabismus), internal organs (kidney, heart, and gastrointestinal tract), genitalia, and heart. Infant mortality associated with thalidomide embryopathy is estimated to be as high as 40%. Thalidomide is contraindicated in pregnancy and pregnancy prevention is recommended in women under treatment.
Thanatophoric dysplasia type 1 (ORPHA:1860)
A form of thanatophoric dysplasia characterized by prenatal onset of growth deficiency of the limbs of less than 5%, bowed femurs (like a telephone receiver), shortened ribs, and platyspondyly. Fetal MRI can identify temporal lobe abnormalities and a narrow foramen magnum. Postnatally, distinctive facial features include macrocephaly, large anterior fontanel, frontal bossing, midface hypoplasia, proptosis, and low nasal bridge. Neonates usually die shortly after birth due to respiratory insufficiency and/or spinal cord/brain stem compression.
Thanatophoric dysplasia type 2 (ORPHA:93274)
A form of thanatophoric dysplasia characterized by prenatal onset of micromelia with straight femurs, platyspondyly, narrow thorax, and cloverleaf skull with increased risk of hydrocephalus and neurological complications. Fetal MRI can identify temporal lobe abnormalities and a narrow foramen magnum. Postnatally, distinctive facial features include macrocephaly, frontal bossing, midface hypoplasia, low nasal bridge, large anterior fontanel, and proptosis. Neonates usually die shortly after birth due to respiratory insufficiency and/or spinal cord/brain stem compression.
Theca steroid-producing cell malignant tumor of ovary, not further specified (ORPHA:99917)
A rare malignant sex cord stromal tumor of ovary of unknown histological lineage, occurring in adult women, characterized, in most cases, by manifestations of androgen excess (hirsutism, hair loss, amenorrhea, or oligomenorrhea) and, occasionally, Cushing syndrome.
Thiamine-responsive encephalopathy (ORPHA:199348)
Thiamine-responsive encephalopathy is a Wernicke-like encephalopathy (see this term) characterized by seizures responsive to high doses of thiamine.
Epidemiology
Two cases have been described so far.
Clinical description
Clinical features include epilepsy, nystagmus, ophthalmoplegia and ataxia.
Etiology
The disease results from mutations in the SLC19A3 gene, encoding a thiamine transporter.
Genetic counseling
Transmission is autosomal recessive.

                            Last update: 
                            October 2009
Thiamine-responsive maple syrup urine disease (ORPHA:268184)
Thiamine-responsive maple syrup urine disease (thiamine-responsive MSUD) is a less severe variant of MSUD (see this term) that manifests with a phenotype similar to intermediate MSUD (see this term) but that responds positively to treatment with thiamine.
Epidemiology
MSUD has an estimated incidence of 1/150,000 live births. The thiamine-responsive type appears to be very rare.
Clinical description
Thiamine-responsive MSUD is poorly characterized. It appears to usually present after infancy with a phenotype very similar to that seen in intermediate MSUD (see this term). Manifestations include feeding problems, poor growth, maple syrup odor in urine and developmental delay. Older children usually present with learning difficulties. Like classic MSUD (see this term), physiological stress can result in acute decompensation with anorexia, nausea, vomiting (at all ages), ataxia (in infants/toddlers), cognitive impairment, sleep disturbances, hallucinations, hyperactivity, mood swings, acute / focal dystonia and choreoathetosis (in adults) that can progress to stupor, coma and cerebral edema, if untreated. Thiamine (doses of 10-1000 mg per day) has improved the leucine tolerance in the few reported cases of this MSUD subtype, but some dietary branched-chain amino-acid (BCAA) restriction remains necessary.
Etiology
MSUD is due to mutations in the genes encoding 3 of the 4 subunits of branched-chain 2-ketoacid dehydrogenase (BCKAD) complex. The genes are BCKDHA (19q13.1-q13.2), encoding E1a; BCKDHB (6q14.1), encoding E1b; and DBT (1p31), encoding E2 respectively. Mutations lead to an accumulation of BCAAs (especially leucine) and branched-chain alpha-ketoacids. In thiamine-responsive MSUD, mutations in DBT predominate.
Genetic counseling
Inheritance is autosomal recessive and genetic counseling is possible.

                            Last update: 
                            April 2014


                            - Expert reviewer(s): 
                            Dr Bridget WILCKEN
Thickened earlobes-conductive deafness syndrome (ORPHA:2405)
Thickened earlobes-conductive deafness syndrome is characterized by microtia with thickened ear lobes, micrognathia and conductive hearing loss due to congenital ossicular anomalies. It has been described in two families. The mode of inheritance is autosomal dominant.
Thiel-Behnke corneal dystrophy (ORPHA:98960)
Thiel-Behnke corneal dystrophy (TBCD) is a rare form of superficial corneal dystrophy characterized by sub-epithelial honeycomb-shaped corneal opacities in the superficial cornea, and progressive visual impairment.
Epidemiology
Prevalence of this form of corneal dystrophy is not known. Cases have been reported in Germany, the USA and in other countries.
Clinical description
Corneal erosions develop in the first and second decade of life and cause ocular discomfort and pain. The erosions recur and vision gradually becomes impaired.
Etiology
Thiel-Behnke corneal dystrophy appears to be caused by mutation in the TGFBI gene (5q31), like Reis-Bücklers corneal dystrophy. However, there appears to be genetic heterogeneity as another locus has also been identified on chromosome 10 (10q23-q24).
Diagnostic methods
Histological examinations reveal a variable thickness of the corneal epithelium. The epithelial basal lamina and Bowman layer display variable degenerative changes. Irregular subepithelial collagenous tissue is also found.
Differential diagnosis
TBCD is clinically similar to Reis-Bücklers corneal dystrophy (RBCD, see this term), but generally has a less severe course. Tissue examination or molecular genetic analysis can be used to differentiate TBCD and RBCD.
Genetic counseling
This entity has an autosomal dominant mode of inheritance.
Management and treatment
The pathologic corneal tissue can be excised surgically or with an eximer laser.

                            Last update: 
                            May 2012


                            - Expert reviewer(s): 
                            Dr Gordon KLINTWORTH
Thiemann disease, familial form (ORPHA:3314)
A very rare genetic necrotic bone disorder characterized clinically by painless swelling of the proximal interphalangeal joints associated with osteonecrosis of epiphyses followed by osteoarthritic changes, with onset before 25 years of age and often a benign course.
Thin ribs-tubular bones-dysmorphism syndrome (ORPHA:1506)
An extremely rare, lethal, primary bone dysplasia characterized by thin ribs, thin long bones, high-arched palate and facial features of frontal bossing and low-set, posteriorly rotated ears. Bilateral cryptorchidism may be also observed. There have been no further descriptions in the literature since 1990.
Thinking seizures (ORPHA:166424)
Thinking seizures is a rare neurologic disease characterized by seizures induced by specific cognitive tasks, such as calculation or solving arithmetic problems (e.g. Sudoku puzzle), playing thinking games (e.g. Rubik's cube, chess, cards), thinking, making decisions and abstract reasoning. Idiopathic generalized seizures are mainly involved, but partial epilepsies may, in rare cases, be observed.
Third branchial cleft anomaly (ORPHA:141030)
A rare otorhinolaryngeal malformation characterized by a soft, fluctuant mass, abscess or draining tract along the anterior border of the lower half of sternocleidomastoid muscle, occasionally leading to development of retropharyngeal absces, acute suppurative thyroiditis, stridor, respiratory distress, odynophagia,and dysphagia. Anomaly occurs as a tract from the piriform sinus to the thyroid gland. A third branchial cleft fistula passes superficial to both the superior and recurrent laryngeal nerves, which is the main difference in comparison to the fourth branchial cleft fistula.
Thomas syndrome (ORPHA:3316)
Thomas syndrome is characterised by renal anomalies, cardiac malformations and cleft lip or palate. It has been described in six patients. Transmission was suggested to be autosomal recessive.
Thomsen and Becker disease (ORPHA:614)
A rare, genetic, skeletal muscle channelopathy characterized by slow muscle relaxation after contraction (myotonia).
Epidemiology
Worldwide prevalence is estimated at 1/100,000.
Clinical description
Onset occurs early in life, usually in the first two decades, with myotonia potentially affecting every muscle after contraction, most frequently lower limb and hand muscles. Myotonia usually improves with exercise (e.g. after warm-up). Myotonia congenita may be inherited as an autosomal dominant (Thomsen disease) or recessive (Becker's disease) inheritance, with a more severe and earlier phenotype in recessively inherited disease.
Etiology
Disease is caused by loss of function mutations in the gene encoding the chloride channel, CLCN1 (7q34), that plays a role in muscle cell repolarization.
Diagnostic methods
The clinical diagnosis can easily be confirmed by electromyography (EMG), which reveals myotonic discharges in association with hyperexcitation of the muscle fiber membrane. EMG testing under exercise and cold stress allows detailed characterization of the myotonia and helps orientate the molecular diagnosis. Identification of mutations in the chloride channel gene can be considered as diagnostic.
Differential diagnosis
Steinert myotonic dystrophy, proximal myotonic myopathy and sodium channel channelopathies should be always considered in the differential diagnosis. Steinert myotonic dystrophy and proximal myotonic myopathy represent the most relevant differential diagnosis; these diseases present with fixed muscle weakness and wasting, and multisystem involvement, which are usually not associated to Thomsen and Becker disease, and occasionally may present with only myotonia. In addition, some degree of weakness may be observed in Thomsen and Becker disease, especially in later disease stages. Sodium muscle channelopathies may present with myotonia, which may be very similar to that reported in Thomsen and Becker disease or characterized by worsening with exercise, the so-called ''paradoxical myotonia'' (paramyotonia congenita).
Genetic counseling
The mode of transmission may be autosomal dominant (Thomsen myotonia) or autosomal recessive (Becker myotonia). Although some clinical and EMG clues may help distinguish Thomsen from Becker disease, genetic counselling should be proposed and the results of the molecular analysis should be interpreted with care as the same mutations have been associated with both dominant and recessive modes of transmission depending on the family studied.
Management and treatment
Treatment revolves around sodium channel blocking agents such as mexiletine hydrochloride (indication approved in Europe), carbamazepine, phenytoin, ranolazine or lamotrigine.
Prognosis
Myotonia congenital prognosis is relatively good, with normal life expectancy. Becker disease is considered more severe than Thomsen disease.

                            Last update: 
                            September 2019


                            - Expert reviewer(s): 
                            Dr Lorenzo MAGGI  - Dr Renato MANTEGAZZA
Thoracic dysplasia-hydrocephalus syndrome (ORPHA:1861)
A rare syndromic primary bone dysplasia characterized by short ribs with a narrow chest and thoracic dysplasia, mild rhizomelic shortening of the limbs, communicating hydrocephalus, and developmental delay. There have been no further descriptions in the literature since 1987.
Thoracic outlet syndrome (ORPHA:97330)
Thoracic outlet syndrome (TOS) is a group of disorders characterized by paresthesias, pain and weakness of the upper extremities due to compression, tension or inflammation of the neurovascular bundle as it passes through the thoracic outlet. There are 3 forms of TOS with different clinical pictures and etiologies: neurogenic TOS (NTOS) that can be divided into true or disputed forms, arterial TOS (ATOS) and venous TOS (VTOS) (see these terms).
Epidemiology
The diagnosis of TOS remains controversial so the true incidence is unknown. Neurogenic TOS is the most frequently observed form accounting for 95% of all cases with 99% of these being disputed NTOS.
Clinical description
Compression typically occurs at the interscalene triangle, the costoclavicular space between the first thoracic rib and clavicle, or the subcoracoid space beneath the pectoralis minor tendon causing pain, paresthesias and weakness in the upper extremities. Patients are unable to maintain the position of opening and closing hands while arms are in an elevated position for 3 minutes (the Roos test).
Etiology
Depending on the subtype, TOS is due to subclavian vein obstruction (in VTOS), subclavian artery compression (in ATOS) or lower trunk brachial plexus compression, scarring of scalene muscles, poor posture or a congenital anomaly (in NTOS).

                            Last update: 
                            May 2013


                            - Expert reviewer(s): 
                            Dr Joseph FEINBERG  - Dr Paul SCHOLTEN
Thoraco-abdominal enteric duplication (ORPHA:1759)
Thoraco-abdominal enteric duplication is a rare, syndromic intestinal malformation characterized by single or multiple smooth-walled, often tubular, cystic lesions, which on occasion contain ectopic gastric mucosa, located in the thorax (usually in the posterior mediastinum and to the right of the midline) and in the abdomen. Infants usually present with respiratory distress and older patients with heartburn, abdominal pain, vomiting and/or melena. Vertebral anomalies in the lower cervical spine, with CNS involvement, are frequently present and complications, such as bowel obstruction, perforation and intussusception, have also been reported.
Thoracolaryngopelvic dysplasia (ORPHA:3317)
Thoracolaryngopelvic dysplasia is a short-rib dysplasia characterized by thoracic dystrophy, laryngeal stenosis and a small pelvis.
Epidemiology
Prevalence is unknown but less than 10 cases have been reported in the literature so far.
Clinical description
Patients present with severe respiratory distress (requiring intubation) during the neonatal period. The rib shortening is less severe than in Jeune syndrome (see this term) and the thorax is characteristically small, narrow and bell-shaped. The pelvis is reduced in all dimensions and the combination of the thorax anomalies and the small pelvis give the appearance of a protruding abdomen. Subglottic stenosis has also been described but it remains unclear whether this is a congenital anomaly or is secondary to long-term intubation. In addition, several cases of thoracopelvic dysostosis (without laryngeal involvement) have been described, which could represent heterogeneous expression of the same syndrome or a distinct entity.
Genetic counseling
Transmission is autosomal dominant.

                            Last update: 
                            November 2008
Thoracomelic dysplasia (ORPHA:1803)
A rare primary bone dysplasia disorder characterized by a bell-shaped thorax, disproportionate short stature, pelvic hypoplasia, dislocatable radial heads and elongated distal fibulae. No acetabular spurs nor phalangeal cone-shaped epiphyses are present and osseous manifestations tend to normalize with age. There have been no further descriptions in the literature since 1988.
Thrombocythemia with distal limb defects (ORPHA:329319)
Thrombocythemia with distal limb defects is a rare, genetic syndrome with limb reduction defects characterized by thrombocytosis, unilateral transverse limb defects (ranging from absence of phalanges to absence of hand or forearm) and splenomegaly.
Thrombomodulin-related bleeding disorder (ORPHA:436169)
A rare genetic coagulation disorder characterized by marked bleeding tendency and posttraumatic bleeding with easy bruising, soft tissue and muscle bleeding, hemarthroses, and menorrhagia due to an increase of soluble thrombomodulin in plasma with subsequent protein C activation and reduction of thrombin generation within a potential thrombus. Abnormal laboratory findings include markedly elevated plasma thrombomodulin, reduced prothrombin consumption, and decreased thrombin generation.
Thumb deformity-alopecia-pigmentation anomaly syndrome (ORPHA:2251)
Thumb deformity-alopecia-pigmentation anomaly syndrome is a rare, genetic, congenital limb malformation syndrome characterized by short stature, sparse scalp hair, hypoplastic, proximally-placed thumbs, and skin hyperpigmentation with areas of 'raindrop' depigmentation. Presence of a single, upper central incisor has also been reported. There have been no further descriptions in the literature since 1988.
Thumb stiffness-brachydactyly-intellectual disability syndrome (ORPHA:1078)
A rare, genetic, congenital limb malformation syndrome characterized by bilateral thumb ankylosis, type A brachydactyly and mild to moderate intellectual disability. Patients present thumb stiffness and abnormalities of the metacarpal bones, frequently associated with mild facial dysmorphism and signs of obesity. There have been no further descriptions in the literature since 1990.
Thygeson superficial punctate keratitis (ORPHA:519406)
A rare disorder of the anterior segment of the eye characterized by chronic recurrent epithelial keratitis manifesting with groupings of small, slightly elevated, ovoid, grayish-white intraepithelial opacities, usually located in the central cornea. Patients present with photophobia, tearing, foreign body sensation, and blurred vision. The condition is typically bilateral, takes a relapsing-remitting course, and is mostly self-limiting after a few years.