TaoMedAI/RareMedData huggingface dataset:
Familial thrombocytosis (ORPHA:71493)
Familial thrombocytosis is a type of thrombocytosis, a sustained elevation of platelet numbers, which affects the platelet/megakaryocyte lineage and may create a tendency for thrombosis and hemorrhage but does not cause myeloproliferation.
Epidemiology
The prevalence of familial thrombocytosis is not known.
Clinical description
The disease usually presents at birth but can be discovered at any time during life and thus can affect all ages. Patients present with thrombocytosis which is often discovered on a routine blood test. The clinical presentation is similar to sporadic essential thrombocythemia (ET; see this term) and may include impaired microcirculation resulting in brief episodes of fainting and dizziness, an increased risk of thrombotic events, hemorrhage, and mild splenomegaly. Patients with mutations in the MPL gene also experience frequent development of bone marrow fibrosis and seem to be free of hemorrhagic complications. The course of the disease is milder than sporadic ET and is devoid of the risk of leukemic transformation or progression toward myelofibrosis with myeloid metaplasia.
Etiology
Familial thrombocytosis is caused by germline mutations in the THPO gene (3q26.3-q27) or in the MPL (MPL S505N) gene (1p34)
Diagnostic methods
Diagnosis is based on the observation of elevated levels of platelets (over 450 x 109/L) and the elimination of secondary causes of thrombocythemia. Genetic testing is required to confirm the diagnosis.
Differential diagnosis
Differential diagnoses include causes of thrombocytosis with myeloproliferative neoplasm including chronic myeloid leukemia, polycythemia vera, primary myelofibrosis, sporadic or familial ET and myelodysplasic disorders with thrombocytosis including sideroblastic anemia or 5q- syndrome (see these terms), although these can be excluded by the presence of myeloproliferation. Differential diagnoses also include causes of secondary thrombocytosis including iron deficiency, malignancy, chronic inflammatory disease, splenectomy or aspleny and protracted marrow regeneration.
Genetic counseling
Transmission is autosomal dominant with high penetrance.
Management and treatment
Treatment is based on low dose aspirin at diagnosis. There is no consensus for using platelet lowering therapy despite an increased risk of thrombosis. Patients may have an increased risk of thrombotic events and hemorrhage.
Prognosis
The predominant clinical feature is impaired microcirculation resulting in brief episodes of fainting and dizziness responding well to aspirin when the THPO gene is mutated and an increased risk of thrombosis and a frequent development of marrow fibrosis when MPL gene is mutated. All these may affect life expectancy.

                            Last update: 
                            March 2010


                            - Expert reviewer(s): 
                            Pr Jean BRIERE
Familial thrombomodulin anomalies (ORPHA:3324)
A rare, life-threatening, genetic coagulation disorder characterized by an increased risk of blood clot formation in several members of a family due to a thrombomodulin gene mutation. Patients may manifest with venous thromboembolic disease, premature myocardial infarction and/or arterial thrombosis.
Familial thyroglossal duct cyst (ORPHA:93953)
A very rare inherited form of TDC characterized by a mass measuring 3 cm in diameter or less in the midline area of the neck.
Familial tumoral calcinosis (ORPHA:53715)
A phosphocalcic metabolism anomaly, occuring particularly among younger age groups, characterized by the presence of calcified masses in the juxta-articular regions (hip, elbow, ankle and scapula) without joint involvement. Histologically, lesions display collagen necrobiosis, followed by cyst formation and a foreign-body response with calcification. Two forms have been described: normocalcemic tumoral calcinosis and familial tumoral calcinosis.
Familial vesicoureteral reflux (ORPHA:289365)
Familial vesicoureteral reflux is a rare, non-syndromic urogenital tract malformation characterized by the familial occurrence of retrograde flow of urine from the bladder into the ureter and sometimes the kidneys. Patients may be asymptomatic or may present with recurrent, sometimes febrile, urinary tract infections that, in case of acute pyelonephritis, may lead to serious complications (renal scarring, hypertension, renal failure). Spontaneous resolution of the disorder is possible.
Familial visceral myopathy (ORPHA:2604)
Familial visceral myopathy is a rare hereditary myopathic degeneration of both gastrointestinal and urinary tracts that causes chronic intestinal pseudo-obstruction. It usually presents after the first decade of life with megaduodenum, megacystis and symptoms such as abdominal distension and/or pain, vomiting, constipation, diarrhea, dysphagia, and/or urinary tract infections.n.
Farmer's lung disease (ORPHA:99906)
Farmer's lung disease is the main form of occupational hypersensitivity pneumonitis (see this term), caused by chronic inhalation of microorganisms, often thermophilic actinomycetes and less commonly saccharopolyspora rectivirgula, living in mouldy hay, straw, or grain. It is characterized by variable degrees of dyspnea, cough, tiredness, headaches and occasional fever/night sweats, with acute, sub-acute or chronic clinical course
FASTKD2-related infantile mitochondrial encephalomyopathy (ORPHA:166105)
A rare, genetic, mitochondrial oxidative phosphorylation disorder characterized by infantile-onset encephalomyopathy presenting with developmental delay, slowly progressive hemiplegia, intractable epileptic seizures and asymmetrical brain atrophy with dilatation of the ipsilateral ventricle system. Additional features include optic atrophy, mildly increased plasma and/or CSF lactate and decreased cytochrome c oxidase activity in skeletal muscle biopsy.
Fatal congenital hypertrophic cardiomyopathy due to glycogen storage disease (ORPHA:439854)
A rare glycogen storage disease characterized by fetal or neonatal onset of severe cardiomyopathy with non-lysosomal glycogen accumulation and fatal outcome in infancy. Patients present with massive cardiomegaly, severe cardiac and respiratory complications, and failure to thrive. Non-specific facial dysmorphism, bilateral cataracts, macroglossia, hydrocephalus, enlarged kidneys, and skeletal muscle involvement have been reported in some cases.
Fatal familial insomnia (ORPHA:466)
A rare inherited human prion disease characterized by adult onset of progressive disturbance and loss of circadian rhythms, dysautonomia with increased sympathetic activity, and cognitive impairment with fluctuating vigilance, impaired long-term memory, disorientation, and oneiric states. Motor disturbances include myoclonus, cerebellar ataxia, and pyramidal signs. The disease rapidly leads to a somnolent or comatose state and is typically fatal after 9 or 30 months on average (bimodal course). Neuropathologic examination shows marked neuronal loss and gliosis predominantly in thalamic nuclei and inferior olives, while deposition of abnormal prion protein may be relatively sparse.
Fatal infantile cytochrome C oxidase deficiency (ORPHA:1561)
Fatal infantile cytochrome C oxidase deficiency is a very rare mitochondrial disease characterized clinically by cardioencephalomyopathy resulting in death in infancy.
Fatal infantile hypertonic myofibrillar myopathy (ORPHA:280553)
Fatal infantile hypertonic myofibrillar myopathy is a rare, genetic skeletal muscle disease characterized by muscle stiffness and rigidity, hypertonia, weakness, respiratory distress and normal cognition. Patients have persistently elevated creatine kinase and histopathology is typical of myofibrillar myopathy. The manifestation onset follows the short period of normal infantile development and leads to progressive respiratory insufficiency and early death.
Fatal infantile lactic acidosis with methylmalonic aciduria (ORPHA:17)
Fatal infantile lactic acidosis with methylmalonic aciduria is a rare neurometabolic disease characterized by infantile onset of severe encephalomyopathy, lactic acidosis and elevated methylmalonic acid urinary excretion. Clinically it manifests with severe psychomotor delay, hypotonia, failure to thrive, feeding difficulties and dystonia. Epilepsy and multiple congenital anomalies may be associated.
Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 (ORPHA:168566)
Combined oxidative phosphorylation deficiency type 3 is an extremely rare clinically heterogenous disorder described in about 5 patients to date. Clinical signs included hypotonia, lactic acidosis, and hepatic insufficiency, with progressive encephalomyopathy or hypertrophic cardiomyopathy.
Fatal post-viral neurodegenerative disorder (ORPHA:391343)
A rare neuroinflammatory disease characterized by the onset of ataxia, dysarthia and cerebral white matter changes which are triggered by viral infection. Episodic progressive neurodegeneration (manifesting with loss of motor and verbal skills, muscle weakness, further cerebral white matter degeneration and, eventually, death) is observed in the absence of hematopathology, cytokine overproduction, fever, hypertrigliceridemia, hypofibrinogenemia and hyperferritinemia.
FATCO syndrome (ORPHA:2492)
A rare, genetic, congenital limb malformation syndrome characterized by unilateral or bilateral fibular aplasia/hypoplasia, tibial campomelia, and lower limb oligosyndactyly involving the lateral rays. Upper limb oligosyndactyly and cleft lip/palate may also be associated.
Fatty acid hydroxylase-associated neurodegeneration (ORPHA:329308)
Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a very rare, autosomal recessive form of neurodegeneration with brain iron accumulation (NBIA) characterized by childhood-onset focal dystonia, progressive spastic paraplegia that progresses to tetra paresis, ataxia, dysarthria, intellectual decline, and oculomotor disturbances (optic atrophy), accompanied by iron deposition in the globus pallidus.
Fatty acyl-CoA reductase 1 deficiency (ORPHA:438178)
A rare disorder of plasmalogen biosynthesis characterized by syndromic severe intellectual disability with congenital cataracts, early-onset epilepsy, microcephaly, global developmental delay, growth retardation and short stature, and spastic quadriparesis. Dysmorphic facial features may be present, including high-arched eyebrows, flattened nasal root, hypertelorism, and long and smooth philtrum. Rhizomelia is not part of the syndrome. Cerebellar atrophy, white matter abnormalities, and Dandy-Walker malformation have been described on brain imaging.
FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome (ORPHA:404451)
FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by delayed motor development, intellectual disability, dysarthria, pseudobulbar signs, cryptorchidism, and syndactyly associated with a  FLBN1  gene point mutation. Macular degeneration and signs of brain atrophy and spinal cord compression have also been reported.
Feingold syndrome type 2 (ORPHA:391646)
A rare, genetic congenital malformation syndrome characterized by microcephaly, short stature, digital anomalies (brachymesophalangy, fifth finger clinodactyly, syndactyly of toes and hypoplastic thumbs) and mild intellectual disabilities but that lacks the manifestations of gastrointestinal atresia.
Epidemiology
Feingold syndrome type 2 (FS2) is extremely rare with less than 20 patients described in the literature to date.
Clinical description
FS2 patients present with microcephaly, brachydactyly, brachymesophalangy of the second and fifth fingers, hypoplastic thumbs and toe syndactyly as seen in FS1. Mild intellectual disability is also noted. Unlike FS1, patients with FS2 lack any form of gastrointestinal atresia and they do not display short palpebral fissures.
Etiology
FS2 is thought to be caused by a hemizygous deletion in the MIR17HG gene on chromosome 13q31.3. This is the first example of a syndromic development deficit in humans that is caused by a miRNA gene.
Diagnostic methods
Diagnosis is suspected on clinical presentation and can be confirmed by high-resolution CGH (comparative genomic hybridization) arrays.
Differential diagnosis
Differential diagnosis of FS2 includes FS type 1 (FS1), VACTERL association, CHARGE syndrome, brachydactyly type A4 and Fanconi anemia.
Antenatal diagnosis
Prenatal testing is possible in FS2 families with a known MIR17HG mutation or deletion.
Genetic counseling
FS2 is inherited in an autosomal dominant manner; however, most cases arise de novo. Genetic counseling is possible.
Management and treatment
Extensive medical examinations are needed to identify possible anomalies of the heart or kidneys. Management of FS2 typically centers for long-term medical sequelae. Occupational therapy / surgical intervention for finger/toe anomalies may be required. Renal and cardiac anomalies should receive the standard treatments and prophylactic antibiotics may be beneficial. Special education is recommended for children and adults with learning deficits. Hearing loss should equally be monitored by an audiologist. Cochlear implants are possible in certain cases.
Prognosis
Prognosis depends on congenital malformations (especially cardiac and renal anomalies) present. If optimal surgical correction is achievable, the prognosis can be relatively positive, though some patients will continue to be affected by their congenital malformations throughout life.

                            Last update: 
                            August 2020


                            - Expert reviewer(s): 
                            Pr Loïc DE PONTUAL | ITHACA*


                                * European Reference Network
Feingold syndrome (ORPHA:1305)
A rare genetic, congenital malformation syndrome characterized by microcephaly, short stature and numerous digital anomalies (brachymesophanlangy, fifth finger clinodactyly, syndactyly of toes and hypoplastic thumbs), mild learning deficit and short palpebral fissures. The two subtypes are clinically distinguished by the presence (type 1) or absence (type 2) gastrointestinal atresia.
Female infertility due to oocyte meiotic arrest (ORPHA:488191)
A rare genetic female infertility characterized by oocyte maturation arrest during any of the various stages of meiosis I or II. In some patients, first polar body oocytes may be retrieved, but these either show fertilization failure or early embryonic arrest. Affected women have regular menstrual cycles.
Female infertility due to zona pellucida defect (ORPHA:404466)
Female infertility due to zona pellucida defect is a rare, genetic, female infertility disorder characterized by the presence of abnormal oocytes that lack a zona pellucida. Affected individuals are unable to conceive despite having normal menstrual cycles and sex hormone levels, as well as no obstructions in the fallopian tubes or defects of the uterus or adnexa.
Female restricted epilepsy with intellectual disability (ORPHA:101039)
Female restricted epilepsy with intellectual disability is a rare X-linked epilepsy syndrome characterized by febrile or afebrile seizures (mainly tonic-clonic, but also absence, myoclonic, and atonic) starting in the first years of life and, in most cases, developmental delay and intellectual disability of variable severity. Behavioral disturbances (e.g. autistic features, hyperactivity, and aggressiveness) are also frequently associated. This disease affects exclusively females, with male carriers being unaffected, despite an X-linked inheritance.
Femoral-facial syndrome (ORPHA:1988)
Femoral-facial syndrome is characterized by predominant femoral hypoplasia (bilateral or unilateral) and unusual facies.
Epidemiology
To date, 55 cases have been reported in the literature.
Clinical description
Facial features include upslanting palpebral fissures, short nose with broad tip, long philtrum, thin upper lip, micrognathia and cleft palate. The complete syndrome with cleft palate has been reported only in females. The following associated anomalies may be present: vertebral segmentation defects, preaxial polydactyly, ear defects, genitourinary tract abnormalities, lung hypoplasia, dysplastic kidneys, patent arterial duct (see this term). Intellectual development has been reported normal. In two patients, central nervous system anomalies (corticosubcortical atrophy, colpocephaly, partial agenesis of corpus callosum, hypoplasia of the falx cerebri and absent septum pellucidum) have been described. Many patients show asymmetrical changes.
Etiology
Maternal diabetes has been recognized as a causative factor in more than 20% of the reported cases.
Genetic counseling
Majority of cases are sporadic. Familial occurrence has been reported in three cases.

                            Last update: 
                            July 2009


                            - Expert reviewer(s): 
                            Pr Raoul HENNEKAM
Femur-fibula-ulna complex (ORPHA:2019)
A rare congenital limb malformation syndrome characterized by a highly variable combination of congenital anomalies of the femur, fibula, and/or ulna, which can appear along with finger/toe anomalies at the ulnar/fibular side. Limb defects are asymmetrical, with upper limbs more often affected than lower limbs, and the right side of the body more often affected than the left. Abnormalities of the upper limb include amelia, hypoplasia of the humerus, humero-radial synostosis, and malformation of the ulna and ulnar rays. Abnormalities of the lower limb include absence of the proximal part of the femur and absence of the fibula. Axial skeleton, internal organs and intellectual function are usually normal.
Ferro-cerebro-cutaneous syndrome (ORPHA:397922)
Ferro-cerebro-cutaneous syndrome is a rare, genetic, metabolic liver disease characterized by progressive neurodegeneration, cutaneous abnormalities, including varying degrees of ichthyosis or seborrheic dermatitis, and systemic iron overload. Patients manifest with infantile-onset seizures, encephalopathy, abnormal eye movements, axial hypotonia with peripheral hypertonia, brisk reflexes, cortical blindness and deafness, myoclonus and hepato/splenomegaly, as well as oral manifestations, including microdontia, widely spaced and pointed teeth with delayed eruption, and gingival overgrowth.
Fetal akinesia deformation sequence (ORPHA:994)
The fetal akinesia/hypokinesia sequence (or Pena-Shokeir syndrome type I) is characterized by multiple joint contractures, facial anomalies and pulmonary hypoplasia. Whatever the cause, the common feature of this sequence is decreased foetal activity.
Epidemiology
The syndrome is rare: about 100 cases have been described in the literature. About 30% are stillborn, and the majority of those live-born die of the complications of pulmonary hypoplasia.
Clinical description
Failure of normal deglutition results in polyhydramnios, and a lack of movement of the diaphragm and intercostal muscles leads to pulmonary hypoplasia. The lack of normal fetal movement also results in a short umbilical cord and multiple joint contractures. Ulnar deviation of the hands, rocker-bottom feet, camptodactyly, sparse dermal ridges and absence of palmar flexion creases are the other components of the fetal akinesia sequence. The face is expressionless, with hypertelorism, telecanthus and poorly folded, small, and posteriorly angulated ears, and the mouth is small with micrognathia and high-arched palate. Cleft palate and cardiac defects may occur occasionally. Many of these babies are born prematurely, and even when born at term their growth is delayed, they have a short neck and cryptorchidism. If they survive, they are likely to develop short-gut syndrome with malabsorption.
Etiology
The Pena-Shokeir syndrome is not a unitary entity but is etiologically heterogeneous. Maternal myasthenia gravis has been diagnosed in some cases, and experiments in animal models show that curarization of the mother induces fetal akinesia. All plausible causes of fetal immobility should be searched for (myogenic, neurogenic, ischemic/anoxic), with biopsies when possible.
Differential diagnosis
There are similarities between Pena-Shokeir syndrome type I and the trisomy 18 syndrome: both may include multiple ankyloses, camptodactyly, and rocker-bottom feet. Karyotyping permits differential diagnosis.
Antenatal diagnosis
Prenatal diagnosis after the birth of an index case relies on ultrasound, which may reveal polyhydramnios, ankyloses, scalp oedema, and decreased chest movements in a fetus with pulmonary hypoplasia.
Genetic counseling
Autosomal recessive inheritance (with parental consanguinity and/or recurrence in sibs) has been implied in about 50% of the published cases. The heterogeneity makes accurate recurrence risk counselling difficult. A 0.01 to 25% risk for recurrence seems most appropriate in apparently sporadic cases.

                            Last update: 
                            July 2005
Fetal akinesia-cerebral and retinal hemorrhage syndrome (ORPHA:363409)
Fetal akinesia-cerebral and retinal hemorrhage syndrome is a rare, lethal, congenital myopathy syndrome characterized by decreased fetal movements and polyhydraminos in utero and the presence of akinesia, severe hypotonia with respiratory insufficiency, absent reflexes, joint contractures, skeletal abnormalities with thin ribs and bones, intracranial and retinal hemorrhages and decreased birth weight in the neonate.
Fetal alcohol syndrome (ORPHA:1915)
Fetal alcohol syndrome (FAS) is a rare malformation syndrome caused by excessive maternal consumption of alcohol during pregnancy. It is characterized by prenatal and/or postnatal growth deficiency (weight and/or height <10th percentile), a unique cluster of minor facial anomalies (short palpebral fissures, flat and smooth philtrum, and thin upper lip) and severe central nervous system (CNS) abnormalities including microcephaly, and cognitive and behavioral impairment (intellectual disability, deficit in general cognition, learning and language, executive function, visual-spatial processing, memory, and attention).
Fetal carbamazepine syndrome (ORPHA:370076)
Fetal carbamazepine syndrome is a drug-related embryofetopathy that can occur when an embryo/fetus is exposed to carbamazepine and that is characterized by facial dysmorphism, with some similarities to that seen in fetal valproate syndrome (see this term), such as epicanthal folds, upward slanting palpebral fissures, short nose, micrognathia and malar hypoplasia, as well as nail dysplasia and major anomalies including cleft lip/palate, neural tube defects and cardiac anomalies. In utero exposure to carbamazepine, in combination with valproate, has been associated with significant developmental delay (particularly affecting verbal intelligence) and a high rate of congenital anomalies.
Fetal cytomegalovirus syndrome (ORPHA:294)
A fetopathy that is likely to occur when a cytomegalovirus (CMV) infected pregnant woman transmits the virus in utero. Children born with congenital CMV infection may present with hepatomegaly, splenomegaly, jaundice, pneumonitis, fetal growth retardation, petechiae, purpura, and thrombocytopenia. Congenital CMV infection can equally result in major neurological sequelae, including microcephaly, intracranial calcifications, sensorineural hearing loss, chorioretinitis, intellectual and motor disabilities, and seizure disorders. CMV disease sequelae caused by a primary infection are usually more severe than those caused by the reactivation of a latent infection.