TaoMedAI/RareMedData huggingface dataset:
Pontiac fever (ORPHA:99748)
Pontiac fever (PF) is a mild form of legionellosis (see this term) manifesting with flu-like symptoms such as nausea, myalgia, fever, cough and headache but without pneumonia.
Epidemiology
The incidence is unknown. Due to the disease's mild and non-specific manifestations it is thought to be underreported. PF is characterised by a high attack rate (number of patients affected / number of people exposed) of up to 95%.
Clinical description
Pontiac fever has a short incubation period ranging from 30-90 hours after infection and affects mainly adults but also children. The disease manifests as an influenza-like syndrome with fever, headache, myalgia and fatigue. In some cases, patients may also experience thoracic pain, dyspnea, diarrhea and vomiting, ocular redness with photophobia and arthralgia. These symptoms usually last 2-7 days and patients recover without treatment.
Etiology
PF is caused by an infection with Legionella pneumophila and Legionella non-pneumophila by inhalation of aerosols from contaminated water, most frequently from showers, whirlpools, spas and hot tubs. The bacteria are found in wet soil and water. It is currently unknown why infection with Legionella evolves into LD or PF in any given case, but as PF is usually observed in immunocompetent patients, immune system status could play a role.
Diagnostic methods
Laboratory diagnosis is rarely performed and is usually done retrospectively by detecting seroconversion or high titers of antibody to Legionella in serum samples. The diagnosis can also be made by detection of the L. pneumophila antigen in urine samples.
Differential diagnosis
Influenza closely resembles PF and must therefore be excluded.
Management and treatment
No treatment is needed for PF and recovery without treatment is the rule.
Prognosis
There is no fatality associated with PF.

                            Last update: 
                            May 2012


                            - Expert reviewer(s): 
                            Dr Sophie JARRAUD
Pontine autosomal dominant microangiopathy with leukoencephalopathy (ORPHA:477749)
A rare genetic cerebral small vessel disease characterized by recurrent ischemic strokes, often with a predilection for the pons, with typical onset in the fourth or fifth decade of life. Patients present progressive cognitive and motor impairment with pyramidal, bulbar, and cerebellar symptoms, among others. Brain imaging shows multiple lacunar infarcts, typically with involvement of the pons, as well as variable leukoencephalopathy of the cerebral hemispheres.
Pontine tegmental cap dysplasia (ORPHA:269229)
A rare, central nervous system malformation characterized by specific pattern of congenital anomalies affecting the pons, medulla, and cerebellum. Clinical manifestations of multiple cranial nerves deficits, pyramidal and cerebellar signs include neonatal hypotonia, ataxia, sensorineural deafness, reduced vision, language and speech disorders, feeding and swallowing difficulties, facial paralysis and intellectual disability. Various cardiac, gastrointestinal, genitourinary and skeletal defects have been sometimes reported.
Pontocerebellar hypoplasia type 10 (ORPHA:411493)
A rare, genetic, pontocerebellar hypoplasia subtype characterized by severe psychomotor developmental delay, progressive microcephaly, progressive spasticity, seizures, and brain abnormalities consisting of mild atrophy of the cerebellum, pons and corpus callosum and cortical atrophy with delayed myelination. Patients may present dysmorphic facial features (high arched eyebrows, prominent eyes, long palpebral fissures and eyelashes, broad nasal root, and hypoplastic alae nasi) and an axonal sensorimotor neuropathy.
Pontocerebellar hypoplasia type 3 (ORPHA:97249)
A rare, genetic form of pontocerebellar hypoplasia (PCH) characterized by neocortical and pontocerebellar hypoplasia with pons and cerebellum equally affected and that clinically manifests with neonatal hypotonia and impaired swallowing followed by seizures, optic atrophy and short stature from infancy onward. Movement disorders, as seen in other forms of PCH, are absent.
Epidemiology
Pontocerebellar hypoplasia type 3 (PCH3) is reported in only 3 families.
Clinical description
Neonatally, PCH3 is characterized by hypotonia and impaired swallowing. From infancy onwards, the main features of PCH3 include progressive microcephaly with brachycephaly, optic atrophy, seizures during the first year of life, severe developmental delay, truncal hypotonia, with increased limb deep tendon reflexes and signs of spasticity of the limbs. Other characteristics such as facial dysmorphism (low set ears and prominent eyes), short stature and low weight are also reported. None of the clinical findings are specific. Characteristic movement disorders, as seen in PCH type 2, appear to be absent.
Etiology
Mutations in the PCLO gene (7q21.11) has been identified in a family from the Sultanate of Oman. It is however unclear if PCLO mutations are causative in the other reported PCH3 families reported in literature. PCH3 is inherited in an autosomal recessive manner.
Diagnostic methods
MRI demonstrates neocortical and pontocerebellar hypoplasia with pons and cerebellum equally affected, a small brainstem, prominent sulci and lateral ventricles and decreased cerebral white matter volume. Genetic testing is recommended to confirm the diagnosis.
Differential diagnosis
Due to phenotypic overlap, other subtypes of PCH should be considered, as well as mutations in the CASK gene. Congenital disorder of glycosylation type 1A (CDG1A) caused by mutations in the PMM2 gene can resemble PCH.
Antenatal diagnosis
Prenatal detection of PCH by ultrasound is unreliable, since cerebellar abnormalities are often not detected at time of the routine screening for structural abnormalities at 20 weeks of gestation. In families in which the causal mutation is detected, prenatal testing or pre-implantation genetic diagnosis (PGD) should be offered.
Genetic counseling
PCH3 is inherited in an autosomal recessive manner. Genetic counseling is recommended for families of individuals with PCH3. For parents of an affected individual, there is a 25% recurrence risk of having another affected child.
Management and treatment
Treatment is symptomatic in PCH.
Prognosis
There is no information on life expectancy, but reported PCH3 patients do not appear to regress.

                            Last update: 
                            January 2021


                            - Expert reviewer(s): 
                            Pr F. [Frank] BAAS  - Dr Tessa VAN DIJK
Pontocerebellar hypoplasia type 4 (ORPHA:166063)
A severe, genetic form of pontocerebellar hypoplasia (PCH) characterized by delayed neocortical maturation with underdeveloped cerebral hemispheres and pontocerebellar hypoplasia and a severely affected vermis. Clinically, the disorder manifests with prenatal onset of polyhydramnios and contractures followed by hypertonia, severe clonus, primary hypoventilation leading to an early postnatal death.
Epidemiology
Pontocerebellar hypoplasia type 4 (PCH4) has been reported in 10 families to date.
Clinical description
PCH4 is characterized prenatally by polyhydramnios. Neonates present with microcephaly, central apnea requiring respiratory support, dysmorphism (sloping forehead, midface hypoplasia, micrognathia), congenital arthrogryposis (50%), severe clonus, and hypertonia. Weaning from mechanical ventilation is difficult and usually fails. Survival beyond the neonatal period is rare.
Etiology
PCH4 is caused by a compound heterozygosity for p.A307S plus non-sense or splice site mutations in the TSEN54 gene (17q25.1).
Diagnostic methods
MRI (usually performed at autopsy) demonstrates microcephaly due to delayed neocortical maturation with underdeveloped cerebral hemispheres, increased volume of extracerebral cerebrospinal fluid, wide midline cava, pontocerebellar hypoplasia with large denuded areas without folia of the cerebellar hemispheric cortex and a severely affected vermis. Genetic testing is recommended to confirm the diagnosis.
Differential diagnosis
Other types of PCH at the severe end of the spectrum should be considered, such as severe forms of PCH1 or SLC25A46-related PCH.
Antenatal diagnosis
In families in which the causal mutation is detected, prenatal genetic testing or pre-implantation genetic diagnosis should be offered. In general, prenatal detection of PCH by ultrasound is unreliable, since cerebellar abnormalities are often not detected at time of the routine screening for structural abnormalities at 20 weeks of gestation.
Genetic counseling
PCH4 is inherited in an autosomal recessive manner. Genetic counseling is recommended for families of individuals with PCH4. For parents of an affected individual, there is a 25% recurrence risk of having another affected child.
Management and treatment
Treatment is symptomatic in PCH.
Prognosis
Survival beyond the neonatal period is rare in PCH4.

                            Last update: 
                            January 2021


                            - Expert reviewer(s): 
                            Pr F. [Frank] BAAS  - Dr Tessa VAN DIJK
Pontocerebellar hypoplasia type 6 (ORPHA:166073)
A rare, genetic form of pontocerebellar hypoplasia (PCH) characterized by neocortical and severe cerebral cortical atrophy associated with pontocerebellar hypoplasia with the pons and cerebellum equally affected. Clinically the disorder manifests at birth with hypotonia, clonus, epilepsy, impaired swallowing and from infancy by progressive microcephaly, spasticity and lactic acidosis.
Epidemiology
Pontocerebellar hypoplasia type 6 (PCH6) is reported in at least 31 cases to date.
Clinical description
PCH6 manifests at birth by generalized hypotonia, lethargy and dysphagia. The clinical profile is characterized from infancy by a profound developmental delay, progressive microcephaly, hypotonia or spasticity and treatment-resistant epilepsy.
Etiology
PCH6 is caused by nonsense, missense and splice site mutations in the mitochondrial arginyl-transfer RNA synthetase (RARS2) gene located to 6q16.1.
Diagnostic methods
MRI demonstrates neocortical and severe cerebral cortical atrophy (more severe than in other types of PCH) as well as pontocerebellar hypoplasia with the pons and cerebellum equally affected. In some patients, early MRI is normal or only shows mild vermal hypoplasia, followed by rapidly progressive brain atrophy. Lactic acid is elevated in cerebrospinal fluid in the majority of patients, which can be accompanied by respiratory chain enzyme deficiency in muscle or fibroblasts. Genetic testing is recommended to confirm the diagnosis
Differential diagnosis
Due to phenotypic overlap, other subtypes of PCH should be considered, as well as mutations in the genes encoding mitochondrial aminoacyl-tRNA synthetases, which can also cause early onset mitochondrial epileptic encephalopathies.
Antenatal diagnosis
Prenatal detection of PCH by ultrasound is unreliable, since cerebellar abnormalities are often not detected at time of the routine screening for structural abnormalities at 20 weeks of gestation. In families in which the causal mutation is detected, prenatal genetic testing or pre-implantation genetic diagnosis should be offered.
Genetic counseling
PCH6 is inherited in an autosomal recessive manner. Genetic counseling is recommended for families of individuals with PCH6. For parents of an affected individual, there is a 25% recurrence risk of having another affected child.
Management and treatment
Treatment is symptomatic in PCH.
Prognosis
Prognosis is poor, exact life expectancy is unknown but in most cases does not exceed infancy.

                            Last update: 
                            January 2021


                            - Expert reviewer(s): 
                            Pr F. [Frank] BAAS  - Dr Tessa VAN DIJK
Pontocerebellar hypoplasia type 7 (ORPHA:284339)
Pontocerebellar hypoplasia type 7 (PCH7) is a novel very rare form of pontocerebellar hypoplasia (see this term) with unknown etiology and poor prognosis reported in four patients and is characterized clinically during the neonatal period by hypotonia, no palpable gonads, micropenis and from infancy by progressive microcephaly, apneic episodes, poor feeding, seizures and regression of penis. MRI demonstrates a pontocerebellar hypoplasia. PCH7 is expressed as PCH with 46,XY disorder of sex development (see this term) in individuals with XY karyotype, and may be expressed as PCH only in individuals with XX karyotype.
Pontocerebellar hypoplasia type 8 (ORPHA:324569)
Pontocerebellar hypoplasia type 8 (PCH8) is a novel very rare form of pontocerebellar hypoplasia (see this term) characterized clinically by progressive microencephaly, feeding difficulties, severe developmental delay, although walking may be achieved, hypotonia often associated with increased muscle tone of lower extremities and deep tendon reflexes, joint deformities in the lower extremities, and occasionally complex seizures. PCH8 is caused by a loss-of-function mutation in the CHMP1A gene. MRI demonstrates a pontocerebellar hypoplasia with vermis and hemispheres equally affected and mild to severely reduced cerebral white matter volume with a fully formed very thin corpus callosum.
Pontocerebellar hypoplasia type 9 (ORPHA:369920)
A rare, genetic, non-syndromic pontocerebellar hypoplasia characterized by progressive cerebellum and brainstem atrophy, corpus callosum hypo-/aplasia and progressive post-natal microcephaly. Patients typically present profound global developmental delay, spastic tetraparesis, seizures, cortical visual impairment and, on neuroimaging, abnormal brain morphology that includes pontocerebellar hypoplasia, ''figure of 8'' midbrain appearance, and, more variably, interhemispheric cysts, ventriculomegaly and cerebral dysmyelination.
Porencephaly-cerebellar hypoplasia-internal malformations syndrome (ORPHA:2941)
Porencephaly-cerebellar hypoplasia-internal malformations syndrome is rare central nervous system malformation syndrome characterized by bilateral porencephaly, absence of the septum pellucidum and cerebellar hypoplasia with absent vermis. Additionally, dysmorphic facial features (hypertelorism, epicanthic folds, high arched palate, prominent metopic suture), macrocephaly, corneal clouding, situs inversus, tetralogy of Fallot, atrial septal defects and/or seizures have been observed.
Porencephaly-microcephaly-bilateral congenital cataract syndrome (ORPHA:306547)
A rare, genetic, central nervous system malformation syndrome characterized by bilateral congenital cataracts and severe hemorrhagic destruction of the brain parenchyma with associated massive cystic degeneration, enlarged ventricles and subependymal calcification. Patients typically present generalized spasticity, increased deep tendon reflexes and seizures. Hepatomegaly and renal anomalies have also been reported.
Porokeratosis of Mibelli (ORPHA:735)
A rare skin disease that is characterized by the presence of brownish single or multiple annular plaques of varying size, that are sometimes confluent, with a distinctive sharply-defined keratotic border.
Epidemiology
Porokeratosis of Mibelli (PM) prevalence is unknown. It is more prevalent in males than females with a ratio of 2-3:1.
Clinical description
Disease onset usually occurs in children, adolescents or young adults (sometimes immunosuppressed). It presents with brownish dry hyperkeratotic plaques of varying size that may coalesce. The lesions have a sharply-defined keratotic border and are usually asymptomatic, but rarely pruritic. They most commonly occur on the limbs (hands and feet) but other areas such as the trunk, palms and soles and genitalia can also be affected. Facial and mucosal lesions are rare. In around 7% of cases, PM lesions undergo malignant transformation, mostly toward squamous cell carcinoma, or less commonly, basal cell carcinoma.
Etiology
The exact etiology is unknown but the lesions are thought to originate from the localized expansion of a clone of abnormal keratinocytes. Contributing factors include immunosuppression, exposure to ultraviolet radiation and drugs, as well as genetic factors (mutations in mevalonate kinase gene).
Diagnostic methods
Diagnosis is based on physical examination and a cutaneous biopsy showing the distinctive cornoid lamella, i.e. a narrow, vertical stack of parakeratotic corneocytes within the horny layer seated on a depression of the underlying epidermis.
Differential diagnosis
The main differential diagnoses are actinic keratosis, elastosis perforans serpiginosa, annular lichen planus, circumscribed palmoplantar hypokeratosis, psoriasis, focal palmoplantar keratoderma and Bowen's disease.
Genetic counseling
Autosomal dominant inheritance has been reported, although PM is often sporadic.
Management and treatment
PM lesions can be treated with surgical excision. Alternative, albeit less efficient, options include topical 5-fluorouracil (5-FU), imiquimod, cryotherapy, dermabrasion, carbon dioxide laser ablation and photodynamic therapy. However the lesions often recur after treatment. Regular follow-up is recommended to monitor the development of any possible malignancies, and sun exposure should be limited in order to decrease their risk.
Prognosis
PM is a chronically progressive disease and can have a negative impact on a patient's quality of life due to the presence of lesions. Rarely (in around 7% of cases), long-standing lesions may transform into squamous cell carcinoma, which has exceptionally proven fatal.

                            Last update: 
                            August 2020


                            - Expert reviewer(s): 
                            Pr Jean KANITAKIS
Porokeratosis plantaris palmaris et disseminata (ORPHA:737)
A rare genetic disease which is a rare form of porokeratosis occurring mainly in adolescence and characterized by small pruritic or painful keratotic papules that first appear on the palms and soles, and may gradually spread to other body zones.
Epidemiology
Porokeratosis plantaris palmaris et disseminata (PPPD) prevalence is unknown but it is one of the rarest forms of porokeratosis. The disease is more frequently seen in males.
Clinical description
The disease often begins in adolescence but some cases have presented in adulthood. Keratotic papules are first noticed on the palms and soles but later spread over the entire body, although lesions on the trunk might be less keratotic. The lesions are usually punctate on the palms and soles and annular on the rest of the body with the characteristic hyperkeratotic border. Foot pain is common due to plantar keratoses. Men are more often affected than women.
Etiology
The exact etiology is unknown. A possible locus for PPPD has been found on chromosome 12q24.1-q24.2.
Diagnostic methods
Diagnosis is based on physical examination and a cutaneous biopsy showing the distinctive pathologic finding known as cornoid lamella. The characteristic clinical findings of papular-keratotic, rather than annular, lesions and an initial onset on the palms and soles also aids in the diagnosis.
Differential diagnosis
Differential diagnoses include other (genetic) punctate palmoplantar keratodermas such as acrokeratoelastoidosis of Costa, hyperkeratosis-hyperpigmentation syndrome, punctate palmoplantar keratoderma type 1 and hereditary papulotranslucent acrokeratoderma.
Genetic counseling
PPPD usually follows a dominant (autosomal or X-linked) pattern of inheritance. Sporadic cases have been reported and may be due to spontaneous mutations resulting in abnormal proliferating clones of epidermal cells.
Management and treatment
There is no standard treatment for PPPD. Oral retinoids combined with topical 5-fluorouracil (5-FU) have been successful in reducing the number of lesions in some patients, but relapses are common. Physical methods (shave excision, cryotherapy, curettage, dermabrasion and linear excision) have had varying degrees of success in removing lesions but are not a feasible option in cases where the lesions are generalized.
Prognosis
PPPD has a negative impact on a patient's quality of life as the lesions are tender or painful, limiting the patient's ability to walk, and their treatment is often unsuccessful.

                            Last update: 
                            August 2020


                            - Expert reviewer(s): 
                            Pr Jean KANITAKIS
Porphyria due to ALA dehydratase deficiency (ORPHA:100924)
A rare acute hepatic porphyria characterized by neurovisceral attacks without skin symptoms.
Epidemiology
Fewer than a dozen cases have been reported in the literature to date.
Clinical description
The disease is reported among children. Patients suffer acute neuro-visceral episodes that can last several weeks, manifesting as intense abdominal pain, neurological disorders and psychological disturbances.
Etiology
Doss porphyria is due to a deficiency in delta aminolevulinic acid dehydratase (ALAD, the second enzyme in the heme biosynthesis pathway), which leads to an accumulation of porphyrin precursors (delta aminolevulinic acid, ALA) in the liver. The enzyme deficiency is due to mutations in the ALAD gene (NM_000031) coding for ALAD (to date, 9 mutations known and expressed). Patients most often have a compound heterozygosity. The transmission pattern is autosomal recessive.
Diagnostic methods
The diagnosis is made on the basis of massive accumulation of ALA in the urine, with no increase in PBG. Diagnosis is based on the identification of a causal mutation in the ALAD gene.
Differential diagnosis
Differential diagnosis should consider acute hepatic porphyria (in acute attack situations), type I tyrosinemia, and lead poisoning.
Antenatal diagnosis
Prenatal diagnosis is theoretically possible in families at risk, but is not offered.
Genetic counseling
Genetic counseling is recommended to patients and families to identify individuals at risk of developing or transmitting the disease, and to advise them on measures to take to reduce the risk of an episode It should also be offered to at-risk couples (both individuals are carriers of a heterozygous pathogenic variant) informing them that there is a 25% risk of having an affected child at each pregnancy.
Management and treatment
Administration of human hemin is of limited effectiveness in acute episode as is liver transplantation. In 2020, treatment with weekly blood transfusions and hydroxyurea was successfully attempted.
Prognosis
In some patients, acute attacks are recurrent and disabling, sometimes fatal. In some cases, they can lead to severe paralysis. The disease is often progressive.

                            Last update: 
                            March 2024


                            - Expert reviewer(s): 
                            Dr Neila TALBI | MetabERN*


                                * European Reference Network
Port-wine nevi-mega cisterna magna-hydrocephalus syndrome (ORPHA:2703)
A rare developmental defect during embryogenesis syndrome characterized by a glabellar capillary malformation, congenital communicating hydrocephalus, and posterior fossa brain abnormalities, including Dandy-Walker malformation, cerebellar vermis agenesis, and mega cisterna magna. Seizures are occasionally associated. There have been no further descriptions in the literature since 1979.
Post-transplant lymphoproliferative disease (ORPHA:70568)
A group of rare immunodeficiency-associated lymphoproliferative disorders characterized by lymphoid or plasmacytic proliferations developing in the context of immunosuppression in a recipient of a solid organ or stem cell allograft. The group includes non-destructive post-transplant lymphoproliferative disorders (PTLDs), polymorphic PTLD, monomorphic PTLDs, and classic Hodgkin lymphoma PTLD. Patients may have more than one type of PTLD in a single or in different locations. The most commonly involved sites are lymph nodes, gastrointestinal tract, lungs, and liver, although the disease may occur almost anywhere in the body. In solid organ transplant recipients, PTLD may also involve the allograft.