The average age at the time of diagnosis is 70. [25] Autopsy studies of Chinese, German, Israeli, Jamaican, Swedish, and Ugandan men who died of other causes found prostate cancer in 30% of men in their 50s, and in 80% of men in their 70s. [26] [27] [28] Men with high blood pressure are more likely to develop prostate cancer. [29] A small increase in risk is associated with lack of exercise. [30] Elevated blood testosterone levels [31] may increase risk. ... It reported superior accuracy of Gallium-68 PSMA-11 PET/CT (92% vs 65%), higher significant change in management (28% vs 15%), less equivocal/uncertain imaging findings (7% vs 23%) and lower radiation exposure (10 msV vs 19 mSv). ... Men with high-grade disease (Gleason 8–10) experienced high mortality within 15 years of diagnosis, regardless of their age. [183] Epidemiology [ edit ] Age-standardized death from prostate cancer per 100,000 inhabitants in 2004. [184] no data <4 4–8 8–12 12–16 16–20 20–24 24–2828–32 32–36 36–40 40–44 >44 As of 2012, prostate cancer is the second-most frequently diagnosed cancer (at 15% of all male cancers) [185] and the sixth leading cause of cancer death in males worldwide. [186] In 2010, prostate cancer resulted in 256,000 deaths, up from 156,000 deaths in 1990. [187] Rates of prostate cancer vary widely.
Overview Prostate cancer is cancer that occurs in the prostate. The prostate is a small walnut-shaped gland in males that produces the seminal fluid that nourishes and transports sperm. Prostate cancer is one of the most common types of cancer. Many prostate cancers grow slowly and are confined to the prostate gland, where they may not cause serious harm. However, while some types of prostate cancer grow slowly and may need minimal or even no treatment, other types are aggressive and can spread quickly. Prostate cancer that's detected early — when it's still confined to the prostate gland — has the best chance for successful treatment. Symptoms Prostate cancer may cause no signs or symptoms in its early stages.
Prostate cancer is a common disease that affects men, usually in middle age or later. In this disorder, certain cells in the prostate become abnormal and multiply without control or order to form a tumor. The prostate is a gland that surrounds the male urethra and helps produce semen, the fluid that carries sperm. Early prostate cancer usually does not cause pain, and most affected men exhibit no noticeable symptoms. Men are often diagnosed as the result of health screenings, such as a blood test for a substance called prostate specific antigen (PSA) or a medical procedure called a digital rectal exam.
Motor symptoms caused by dysfunction of the cerebellum Cerebellar ataxia Specialty Neurology Cerebellar ataxia is a form of ataxia originating in the cerebellum . [1] Non-progressive congenital ataxia (NPCA) is a classical presentation of cerebral ataxias. Cerebellar ataxia can occur as a result of many diseases and may present with symptoms of an inability to coordinate balance, gait, extremity and eye movements. [2] Lesions to the cerebellum can cause dyssynergia , dysmetria , dysdiadochokinesia , dysarthria and ataxia of stance and gait. [3] Deficits are observed with movements on the same side of the body as the lesion (ipsilateral). [2] Clinicians often use visual observation of people performing motor tasks in order to look for signs of ataxia. [2] Contents 1 Signs and symptoms 2 Causes 3 Treatment 3.1 Behavioral intervention 4 See also 5 References 6 External links Signs and symptoms [ edit ] Damage to the cerebellum causes impairment in motor skills and can cause nystagmus . Almost a third of people with isolated, late onset cerebellar ataxia go on to develop multiple system atrophy . [4] The cerebellum's role has been observed as not purely motor. It is combined with intellect, emotion and planning. [5] Causes [ edit ] Play media A male with gluten ataxia: previous situation and evolution after 3 months of gluten-free diet. There are many causes of cerebellar ataxia including, among others, gluten ataxia , [6] autoimmunity to Purkinje cells or other neural cells in the cerebellum, [7] CNS vasculitis , multiple sclerosis , infection, bleeding, infarction, tumors, direct injury, toxins (e.g., alcohol), genetic disorders and neurodegenerative diseases (such as progressive supranuclear palsy and multiple system atrophy ).
A rare multiple congenital anomalies syndrome usually characterized by microcephaly, ocular anomalies such as microphthalmia, and apple-peel intestinal atresia. Facial dysmorphism is reported in some cases and may include narrow or sloped forehead, hypertelorism, microphthalmia, dysplastic, edematous deep-set eyes, short palpebral fissures, large or low set ears, broad nasal root, anteverted or broad nasal tip, long philtrum, micrognathia, thin upper vermillion, large mouth and skin tag on the cheek. Motor delay and intellectual disability have been reported. Heart, brain, craniofacial abnormalities, renal hypoplasia and other anomalies (e.g. lower limb edema, thrombocytopenia) are variably present. Rarely, cases without intestinal atresia, microcephaly or developmental delay can be found. Severe lethal cases have also been reported.
A number sign (#) is used with this entry because of evidence that Stromme syndrome (STROMS) is caused by compound heterozygous mutation in the CENPF gene (600236) on chromosome 1q41. Description Stromme syndrome is an autosomal recessive congenital disorder affecting multiple systems with features of a ciliopathy. Affected individuals typically have some type of intestinal atresia, variable ocular abnormalities, microcephaly, and sometimes involvement of other systems, including renal and cardiac. In some cases, the condition is lethal in early life, whereas other patients show normal survival with or without mild cognitive impairment (summary by Filges et al., 2016). Clinical Features Stromme et al. (1993) reported 2 sisters, the offspring of healthy, unrelated parents, who had apple peel jejunal atresia (see 243600), severe microcephaly, and ocular abnormalities.
Targeted analysis for pathogenic variants can include the following: c.156C>A (p.Cys52Ter) is the most frequent pathogenic variant in individuals of Turkish ethnicity and accounts for approximately 28% of pathogenic variants worldwide [Author, review of the literature]. c.1010G>A (p.Cys337Tyr) and c.233G>A (p.Cys78Tyr) are the most common pathogenic variants in the Indian population.
Progressive pseudorheumatoid arthropathy (dysplasia) of childhood (PPAC; PPD) presents as spondyloepiphyseal dysplasia (SED) tarda with progressive arthropathy and is described as a specific autosomal recessive subtype of SED. Epidemiology The prevalence has been estimated at 1/1,000,000 but it is likely to be higher in the Middle East and the Maghreb. Clinical description Most patients present the disease before the age of 8 years (the onset varies between 2 and 11 years). Typically, there are no symptoms in the newborn period. The most common signs at diagnosis are bowing of the legs, muscle weakness, symmetric swelling of the proximal interphalangeal joints. Motion range limitation, deformities and pain develop gradually, and spread to other joints.
A number sign (#) is used with this entry because of evidence that progressive pseudorheumatoid arthropathy of childhood (PPAC) is caused by homozygous or compound heterozygous mutation in the WISP3 gene (603400) on chromosome 6q21. Clinical Features Spranger et al. (1983) described an arthropathy of childhood beginning at about age 3 years with progressive joint stiffness that first affects the hips. Morning stiffness and decreased mobility of the cervical spine suggest rheumatoid arthritis. Swelling of the finger joints is caused not by soft tissue involvement but by osseous distention of the ends of the phalanges. Normal sedimentation rate, negative rheumatoid factor tests, and histologically normal synovium exclude rheumatoid disease.
Progressive pseudorheumatoid dysplasia (PPRD) is a joint disease that worsens over time. This condition is characterized by breakdown (degeneration) of the cartilage between bones (articular cartilage). This cartilage covers and protects the ends of bones, and its degeneration leads to pain and stiffness in the joints and other features of PPRD. PPRD usually begins in childhood, between ages 3 and 8. The first indications are usually an abnormal walking pattern, weakness and fatigue when active, and stiffness in the joints in the fingers and in the knees. Other signs and symptoms that develop over time include permanently bent fingers (camptodactyly), enlarged finger and knee joints (often mistaken as swelling), and a reduced amount of space between the bones at the hip and knee joints.
Progressive pseudorheumatoid disyplasia (PPD) is a disorder of bone and cartilage that affects many joints. It manifests between the age of 3 and 6 years with joint pain and progressive joint stiffness. Major signs and symptoms include stiff joints (contractures), short stature, and widening of the ends of the finger and toe bones as well as other tubular bones. Bony widening at the fingers' joints progresses leading to permanent bending of the fingers (camptodactyly). Spine involvement results in short trunk and hunching of the back (kyphosis).
A number sign (#) is used with this entry because of evidence that Desbuquois dysplasia-2 (DBQD2) is caused by homozygous or compound heterozygous mutation in the XYLT1 gene (608124) on chromosome 16p12. Description Desbuquois dysplasia, which belongs to the multiple dislocation group of disorders, is characterized by dislocations of large joints, severe pre- and postnatal growth retardation, joint laxity, and flat face with prominent eyes. Radiologic features include short long bones with an exaggerated trochanter that gives a 'monkey wrench' appearance to the proximal femur, and advanced carpal and tarsal ossification (summary by Bui et al., 2014). For a discussion of genetic heterogeneity of Desbuquois dysplasia, see DBQD1 (251450). Nomenclature Desbuquois dysplasia had been classified as 'type 1' or 'type 2' based on the presence (type 1) or absence (type 2) of additional hand anomalies, consisting of an extra ossification center distal to the second metacarpal, a delta phalanx, a bifid distal thumb phalanx, and dislocation of the interphalangeal joints.
Desbuquois syndrome (DBQD) is an osteochondrodysplasia characterized by severe micromelic dwarfism, facial dysmorphism, joint laxity with multiple dislocations, vertebral and metaphyseal abnormalities and advanced carpotarsal ossification. Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies. A variant form of DBQD, Kim variant (see these terms), has also been described and is characterized by short stature and articular, minor facial and significant hand anomalies. Epidemiology To date, less than 50 cases have been described in the literature. Clinical description DBQD is characterized by severe micromelic dwarfism, facial dysmorphism (round flat face, prominent eyes, midface hypoplasia, short nose, microstomia, long upper lip with flat philtrum, microretrognathia, often resulting in isolated Pierre Robin syndrome (see this term)), thoracic hypoplasia, kyphoscoliosis, severe joint laxity with dislocation, and osteopenia.
Desbuquois syndrome (DBQD) is a rare type of osteochondrodysplasia (a disorder of the development of bones and cartilage). Characteristics may vary in severity and can include short stature with short extremities, severe joint laxity with dislocation, osteopenia , kyphoscoliosis , distinctive facial characteristics and other abnormalities.Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies. A variant form of DBQD, Kim variant, has been described in 7 patients originating from Korea and Japan, and is characterized by short stature, joint and minor facial anomalies, together with significant hand anomalies with short bones in the hands, long fingers and advanced bone age. DBQD type 1 and Kim variant are caused by mutations in the gene CANT1 . Some cases of DBQD type 2 are caused by mutations in the gene XYLT1 but in other cases the cause is unknown.
A radiograph shows a well-demarcated cyst-like lesion (arrow) in the talus of a person with PLOSL, age 28 years. Paloneva et al [2001]; reprinted with permission from Neurology Neuroradiologic findings (Figure 3, Figure 4, Figure 5) Figure 3.
A number sign (#) is used with this entry because of evidence that polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy-2 (PLOSL2) is caused by homozygous mutation in the TREM2 gene (605086) on chromosome 6p21. Description Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy-2 (PLOSL2), or Nasu-Hakola disease, is a recessively inherited presenile frontal dementia with leukoencephalopathy and basal ganglia calcification. In most cases the disorder first manifests in early adulthood as pain and swelling in ankles and feet, followed by bone fractures. Neurologic symptoms manifest in the fourth decade of life as a frontal lobe syndrome with loss of judgment, euphoria, and disinhibition. Progressive decline in other cognitive domains begins to develop at about the same time.
This article includes a list of general references , but it remains largely unverified because it lacks sufficient corresponding inline citations . Please help to improve this article by introducing more precise citations. ( June 2019 ) ( Learn how and when to remove this template message ) Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy Specialty Medical genetics Causes Mutations in the TREM2 and TYROBP genes Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy is a rare disease characterised by early-onset dementia and multifocal bone cysts. [1] It is also known as Nasu–Hakola disease. Contents 1 Signs and symptoms 2 Genetics 3 Pathopysiology 4 Diagnosis 4.1 Differential diagnosis 4.2 Investigations 5 Treatment 6 Epidemiology 7 History 8 References Signs and symptoms [ edit ] Four stages are recognised in this condition. The first (latent stage) show no symptoms or signs. This stage typically lasts up to the early 20s. This is followed by the osseous stage. This is characterised by recurrent bone pain usually affecting the long bones of the limbs.
A number sign (#) is used with this entry because of evidence that polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy-1 (PLOSL1), also known as Nasu-Hakola disease, is caused by homozygous mutation in the DAP12 gene (TYROBP; 604142) on chromosome 19q13. Description Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy is characterized by presenile dementia along with large-scale destruction of cancellous bones. Initial symptoms, starting in the twenties, are pain and swelling resulting from cysts in the wrists and ankles. Extremity bone fractures could occur with minor trauma. At around 30 years of age, patients gradually develop neuropsychiatric symptoms, including epileptic seizures, agnosia, apraxia, speech disorder, memory disturbance, euphoria, and loss of social inhibitions. The disorder usuallly leads to death in the fifth decade of life (summary by Kondo et al., 2002).
Nasu-Hakola disease (NHD), also referred to as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), is a rare inherited leukodystrophy characterized by progressive presenile dementia associated with recurrent bone fractures due to polycystic osseous lesions of the lower and upper extremities. Epidemiology Over 200 cases have been reported worldwide in the literature, the majority of them being in the Japanese and Finnish population. The prevalence in Finland is estimated between 1/500,000 and 1/1,000,000. Clinical description The disease course is generally divided into four stages: latent, osseous, early neurologic, and late neurologic. After a normal development during childhood (latent stage), the disease starts manifesting during adolescence or young adulthood (typical age of onset 20-30 years) with pain in the hands, wrists, ankles, and feet.
Other conditions to consider in the differential diagnosis Lissencephalies without known gene defects exhibiting two-layered cortex, extreme microcephaly, and cerebellar and pontine hypoplasia [Forman et al 2005] Pontocerebellar hypoplasia in extremely premature infants (gestational age <28 weeks); an acquired phenocopy to be considered [Volpe 2009, Pierson & Al Sufiani 2016] Management Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with EXOSC3 pontocerebellar hypoplasia ( EXOSC3- PCH), the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended.
Osteopathia striata with cranial sclerosis (OS-CS) is a bone dysplasia characterized by longitudinal striations of the metaphyses of the long bones, sclerosis of the craniofacial bones, macrocephaly, cleft palate and hearing loss. Epidemiology Fewer than 100 cases have been reported in the literature. Clinical description The clinical presentation is highly variable even within the same family, ranging from mild skeletal manifestations to multisystem organ involvement. Cardiac malformations (ventricular septal defect, aortic stenosis), developmental delay, cranial nerve palsies, anal malformations, cataracts and nervous system malformations are frequent. Vertebral anomalies (scoliosis, spondylolisthesis), anomalies of extremities (clubfoot, unusually long and thin fingers with clinodactyly of distal phalanges), hypertelorism, frontal bossing, broad nasal bridge, prominent occipital bony protrusion and mild intellectual impairment have also been documented.
Osteopathia striata with cranial sclerosis (OSCS) causes the bones to become unusually hard and thick. The severity of the condition and the symptoms vary significantly from person to person, even within the same family. Features of the condition are generally present at birth. Symptoms may include skeletal abnormalities at the ends of long bones, hardening (sclerosis) of the bones of the head and face, large head size, and cleft palate. Some people with OSCS may also have developmental delay, hearing loss, heart defects, and breathing and feeding difficulties. Osteopathia striata cranial sclerosis is caused by variants in the AMER1 gene and is inherited in an X-linked dominant pattern.
At baseline, 26 (67%) of 39 patients with available photographs had macular atrophy with macular/peripheral flecks; 11 (28%) has macular atrophy without flecks; 1 (2.5%) had numerous flecks without macular atrophy; and 1 (2.5%) had a normal fundus appearance.
A number sign (#) is used with this entry because of evidence that Stargardt disease-3 (STGD3) is caused by heterozygous mutation in the ELOVL4 gene (605512) on chromosome 6q14. For a general phenotypic description and a discussion of genetic heterogeneity of Stargardt disease, see 248200. Clinical Features In most instances macular dystrophy with flecks (Stargardt disease) shows an autosomal recessive pattern of inheritance; see 248200. Cibis et al. (1980) reported an extensive family with an apparently dominant form of macular dystrophy with flecks. Some patients had no flecks. The authors thought there was insufficient evidence to place the disorder in the category of 'cone dystrophy,' and stated that 'cone dystrophy is never associated with the fundus flavimaculatus flecks synonymous with Stargardt's disease.'
Stargardt disease Other names Stargardt macular dystrophy & degeneration, juvenile macular degeneration, fundus flavimaculatus Optical coherence tomography is used for diagnosis of Stargardt's disease. Specialty Ophthalmology Symptoms Blurred vision Usual onset Childhood Duration Lifelong Causes Genetic Diagnostic method Slit-lamp Treatment None Stargardt disease is the most common inherited single-gene retinal disease . [1] It usually has an autosomal recessive inheritance caused by mutations in the ABCA4 gene. Rarely it has an autosomal dominant inheritance due to defects with ELOVL4 or PROM1 genes. It is characterised by macular degeneration that begins in childhood, adolescence or adulthood, resulting in progressive loss of vision. [2] Contents 1 Signs and symptoms 2 Genetics 3 Pathophysiology 4 Diagnosis 5 Treatment 6 Prognosis 7 Epidemiology 8 History 9 Research 10 References 11 External links Signs and symptoms [ edit ] Presentation usually occurs in childhood or adolescence, though there is no upper age limit for presentation. The main symptom is loss of visual acuity, uncorrectable with glasses.
A number sign (#) is used with this entry because Stargardt disease-4 (STGD4) is caused by heterozygous mutation in the prominin-1 gene (PROM1; 604365). For a general phenotypic description and a discussion of genetic heterogeneity of Stargardt disease, see STGD1 (248200). Description Stargardt disease is the most common hereditary macular dystrophy and is characterized by decreased central vision, atrophy of the macula and underlying retinal pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD is most commonly inherited as an autosomal recessive trait (see 248200), but STGD4 is inherited as an autosomal domiant trait (summary by Kniazeva et al., 1999). Clinical Features Kniazeva et al. (1999) studied 26 members of a 3-generation Caribbean kindred with an autosomal dominant Stargardt-like phenotype.
A rare ophthalmic disorder that is usually characterized by a progressive loss of central vision associated with irregular macular and perimacular yellow-white fundus flecks, and a so-called ''beaten bronze'' atrophic central macular lesion. Epidemiology The prevalence is estimated at 1/8,000 - 1/10,000. Both sexes are equally affected. Clinical description The disease typically presents within the first two decades of life, even though symptoms can also appear during adulthood and as late as the seventh decade. Although disease progression and severity varies widely, Stargardt disease (STGD1) is usually characterized by a progressive loss of central vision causing blurry vision and, occasionally, an increasing difficulty to adapt in the dark. Peripheral vision is usually normal. Most affected individuals also have impaired color vision.
Stargardt disease is a genetic eye disorder that causes progressive vision loss. It affects the macula, an area of the retina responsible for sharp, central vision. Vision loss is due to abnormal accumulation of a fatty yellow pigment ( lipofuscin ) in the cells within the macula. People with Stargardt disease also have problems with night vision, and some have problems with color vision. The signs and symptoms of Stargardt disease typically appear in late childhood to early adulthood and worsen over time.
A number sign (#) is used with this entry because galactokinase deficiency is caused by homozygous or heterozygous mutation in the GALK1 gene (604313) on chromosome 17q24. Classic galactosemia (230400) is a distinct disorder caused by mutation in the gene encoding galactose-1-phosphate uridyltransferase (GALT; 606999) on chromosome 9p13. Description Galactokinase deficiency is an autosomal recessive disorder that causes cataract formation in children not maintained on a lactose-free diet. Cataract formation is the result of osmotic phenomena caused by the accumulation of galactitol in the lens (Asada et al., 1999). Clinical Features Gitzelmann (1967) reported juvenile cataracts related to galactokinase deficiency in 2 sibs of a consanguineous Gypsy family, Fanconi had previously reported the cases as instances of 'galactose diabetes;' however, GALT activity in red cells was normal.
Galactosemia , which means “galactose in the blood,” refers to a group of inherited disorders that impair the body's ability to process and produce energy from a sugar called galactose. When people with galactosemia injest foods or liquids containing galactose, undigested sugars build up in the blood. Galactose is present in many foods, including all dairy products (milk and anything made from milk), many baby formulas, and some fruits and vegetables. The impaired ability to process galactose can be due to the deficiency of any of 3 enzymes, caused by mutations in different genes. There are 3 main types of galactosemia which are distinguished based on their genetic causes, signs and symptoms, and severity: Classic galactosemia (type 1) - the most common and severe type, caused by mutations in the GALT gene, and characterized by a complete deficiency of an enzyme called galactose-1-phosphate uridyl transferase (GALT).
Galactosemia Galactose Specialty Endocrinology Galactosemia (British galactosaemia , from Greek γαλακτόζη + αίμα , meaning galactose + blood, accumulation of galactose in blood) is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly. Galactosemia follows an autosomal recessive mode of inheritance that confers a deficiency in an enzyme responsible for adequate galactose degradation. Friedrich Goppert (1870–1927), a German physician, first described the disease in 1917, [1] with its cause as a defect in galactose metabolism being identified by a group led by Herman Kalckar in 1956. [2] Galactosemia was the second disorder found to be detectable through newborn screening methods by Robert Guthrie. [3] Its incidence is about 1 per 60,000 births for people of European ancestry. In other populations the incidence rate differs. Galactosaemia is about one hundred times more common (1:480 births) [4] in the Irish Traveller population. [5] Contents 1 Cause 2 Accumulation of galactose 2.1 Reduction to galactitol 2.2 Oxidation to galactonate 3 Diagnosis 3.1 Types 4 Treatment 5 See also 6 References 7 External links Cause [ edit ] Lactose Glucose Galactose Lactose in food (such as dairy products) is broken down by the enzyme lactase into glucose and galactose . In individuals with galactosemia, the enzymes needed for further metabolism of galactose (Galactokinase and galactose-1-phosphate uridyltransferase) are severely diminished or missing entirely, leading to toxic levels of galactose or galactose 1-phosphate (depending on which enzyme is missing) in various tissues as in the case of classic galactosemia , resulting in hepatomegaly (an enlarged liver ), cirrhosis , kidney failure , cataracts , vomiting , seizure , low blood sugar (hypoglycemia) , lethargy , brain damage , and ovarian failure .
A number sign (#) is used with this entry because galactosemia III is caused by homozygous or compound heterozygous mutation in the UDP-galactose-4-epimerase gene (GALE; 606953) on chromosome 1p36. Description Epimerase-deficiency galactosemia was originally described as a benign condition in which GALE impairment is restricted to circulating red and white blood cells (Gitzelmann, 1972). Fibroblasts, liver, phytohemagglutinin-stimulated leukocyes, and Epstein Barr virus-transformed lymphoblasts from these patients all demonstrated normal or near-normal levels of GALE, leading to the designation 'peripheral' (or 'isolated') epimerase deficiency. A second form of epimerase deficiency became apparent in which a patient, despite normal GALT activity, presented with symptoms reminiscent of classic galactosemia and demonstrated severely impaired GALE activity in both red blood cells and fibroblasts (Holton et al., 1981). This form was designated 'generalized' epimerase deficiency. Openo et al. (2006) demonstrated that epimerase deficiency is in fact not a binary condition but is, rather, a continuum disorder.
Galactosemia is a group of rare genetic metabolic disorders characterized by impaired galactose metabolism resulting in a range of variable manifestations encompassing a severe, life-threatening disease (classic galactosemia), a rare mild form (galactokinase deficiency) causing cataract, and a very rare form with variable severity (galactose epimerase deficiency) resembling classic galactosemia in the severe form (see these terms). Epidemiology Overall prevalence is unknown. The annual incidence of classic galactosemia is estimated to be between 1/40,000 and 1/60,000 in Western countries. Incidence appears to be variable in other ethnic groups with a higher rate reported in the Irish Traveler population possibly due to consanguinity. Clinical description Infants usually develop feeding difficulties, poor weight gain and growth, lethargy, and jaundice in the common severe form of the disorder, i.e. classic galactosemia. The rare, less severe clinical subtype of galactosemia (galactokinase deficiency) causes primarily cataracts while other signs of galactosemia are absent.
Only 97 (47.3%) were thought to meet the diagnostic criteria for Proteus syndrome; 80 cases (39%) clearly did not meet the criteria; and although 28 cases (13.7%) had features suggestive of Proteus syndrome, there were insufficient clinical data to make a diagnosis.
Summary Clinical characteristics. Proteus syndrome is characterized by progressive segmental or patchy overgrowth most commonly affecting the skeleton, skin, adipose, and central nervous systems. In most individuals Proteus syndrome has modest or no manifestations at birth, develops and progresses rapidly beginning in the toddler period, and relentlessly progresses through childhood, causing severe overgrowth and disfigurement. It is associated with a range of tumors, pulmonary complications, and a striking predisposition to deep vein thrombosis and pulmonary embolism. Diagnosis/testing. The diagnosis of Proteus syndrome is based on clinical criteria that include all three general characteristics (mosaic distribution of lesions, sporadic occurrence, progressive course) and additional specific clinical criteria. Identification of a mosaic, somatic, heterozygous pathogenic variant in AKT1 by molecular genetic testing can establish the diagnosis if the clinical criteria are inconclusive.
Proteus syndrome (PS) is a very rare and complex hamartomatous overgrowth disorder characterized by progressive overgrowth of the skeleton, skin, adipose, and central nervous systems. Epidemiology Approximately 120 cases of PS have been reported to date. The prevalence is estimated to be less than 1/1,000,000 live births. Clinical description Neonates usually appear normal at birth. Onset usually occurs from 6-18 months of age with asymmetric overgrowth seen mainly in the hands or feet. Macrodactyly is the most common presenting symptom, along with hemihypertrophy.
Proteus syndrome is a rare condition characterized by overgrowth of the bones, skin, and other tissues. Organs and tissues affected by the disease grow out of proportion to the rest of the body. The overgrowth is usually asymmetric, which means it affects the right and left sides of the body differently. Newborns with Proteus syndrome have few or no signs of the condition. Overgrowth becomes apparent between the ages of 6 and 18 months and gets more severe with age.
Proteus syndrome is characterized by excessive growth of a part or portion of the body. The overgrowth is usually asymmetric, which means it affects the right and left sides of the body differently. Newborns with Proteus syndrome have few or no signs of the disorder. Overgrowth becomes apparent between the ages of 6 and 18 months and becomes more severe with age. It may result in differences in appearance and with time, an increased risk for blood clots and tumors. Some people with Proteus syndrome have neurological abnormalities, including intellectual disability, seizures, and vision loss, as well as distinctive facial features.
The Journal of Laboratory and Clinical Medicine . 21 (6): 619–28. ^ a b c d e f g D Martino; A Tanner; G Defazio; A J Church; K P Bhatia; G Giovannoni; R C Dale (October 2004).
Sydenham's chorea is a neurological disorder characterized by rapid, jerky, irregular, and involuntary movements (chorea), especially of the face and limbs. Additional symptoms may include muscle weakness, slurred speech, headaches, and seizures. Children with Sydenham's chorea often have emotional or behavioral problems such as obsessive-compulsive disorder , distractibility, irritability, and inappropriate outbursts of laughing or crying. Sydenham's chorea mostly affects children and adolescents and usually follows a Streptococcal infection by anywhere form 1-8 months. Sydenham's chorea is one of the major clinical signs of acute rheumatic fever .
Other Features Lopez-Velasco et al. (1997) found that hypertension was present in approximately 43% of patients with active acromegaly and in 28% of patients in whom acromegaly was cured.
Recent research [ edit ] According to NIH clinical trials.gov, research on the port-wine stain and its relation to polymorphisms of RASA1 has commenced in November 2010 and expected to end in November 2019. [28] The purpose of the study is to assess how the port-wine stains can lead to complex syndromes such as PWS.
A number sign (#) is used with this entry because of evidence that Sturge-Weber syndrome can be caused by somatic mosaic mutation in the GNAQ gene (600998) on chromosome 9q21. Nonsyndromic port-wine stains (CMC; 163000) are also caused by somatic mosaic mutation in the GNAQ gene. Description Sturge-Weber syndrome is characterized by an intracranial vascular anomaly, leptomeningeal angiomatosis, most often involving the occipital and posterior parietal lobes. The most common symptoms and signs are facial cutaneous vascular malformations (port-wine stains), seizures, and glaucoma. Stasis results in ischemia underlying the leptomeningeal angiomatosis, leading to calcification and laminar cortical necrosis.
Sturge-Weber syndrome (SWS) is a rare disorder affecting the skin and nervous system. Babies with SWS are born with a birthmark on their face known as a port-wine stain . Port-wine birthmarks are caused by enlarged blood vessels right underneath the skin. People with Sturge-Weber syndrome also have clusters of abnormal blood vessels between the layers of tissue that cover the brain and spine known as leptomeningeal angiomas. They may also have increased pressure in the eyes known as glaucoma. Other symptoms of SWS may include seizures, muscle weakness, developmental and intellectual disability.
Sturge–Weber syndrome Other names Sturge–Weber–Krabbe disease CT scan of Sturge-Weber syndrome Specialty Medical genetics Sturge–Weber syndrome , sometimes referred to as encephalotrigeminal angiomatosis , is a rare congenital neurological and skin disorder. It is one of the phakomatoses and is often associated with port-wine stains of the face, glaucoma , seizures , intellectual disability , and ipsilateral leptomeningeal angioma (cerebral malformations and tumors). Sturge–Weber syndrome can be classified into three different types. Type 1 includes facial and leptomeningeal angiomas as well as the possibility of glaucoma or choroidal lesions. Normally, only one side of the brain is affected. This type is the most common. Type 2 involvement includes a facial angioma (port wine stain) with a possibility of glaucoma developing.
Parkes Weber syndrome (PWS) is a rare congenital condition characterized by a large number of abnormal blood vessels. The main signs and symptoms of PWS typically include a capillary malformation on the skin; hypertrophy (excessive growth) of the bone and soft tissue of the affected limb; and multiple arteriovenous fistulas (abnormal connections between arteries and veins) which can potentially lead to heart failure. There also may be pain in the affected limb and a difference in size between the limbs. Some cases of Parkes Weber syndrome result from mutations in the RASA1 gene, and are inherited in an autosomal dominant manner. In these cases, affected people usually have multiple capillary malformations.
A rare congenital neurocutaneous syndrome defined by a facial capillary malformation or port-wine birthmark (PWB) associated with cerebral and ocular ipsilateral vascular malformations in most of the cases resulting in variable ocular and neurological complications. Epidemiology The birth prevalence in Europe is estimated at around 1/20,000 to 1/50,000. Clinical description The facial port-wine birthmark is present at birth and covers the forehead and/or the upper eyelid (at risk zone). Glaucoma is the most common ocular complication, affecting 30 to 60% of patients with a risk of early visual impairment. Epilepsy is often the first neurological manifestation. Around 80% of patients develop seizures at a median age of 6 months.
Sturge-Weber syndrome is a condition that affects the development of certain blood vessels, causing abnormalities in the brain, skin, and eyes from birth. Sturge-Weber syndrome has three major features: a red or pink birthmark called a port-wine birthmark, a brain abnormality called a leptomeningeal angioma, and increased pressure in the eye (glaucoma ). These features can vary in severity and not all individuals with Sturge-Weber syndrome have all three features. Most people with Sturge-Weber syndrome are born with a port-wine birthmark. This type of birthmark is caused by enlargement (dilatation) of small blood vessels (capillaries) near the surface of the skin.
The patient's son reported slow running in childhood and proximal muscle weakness that became apparent in his teenage years. Physical examination at age 28 showed proximal greater than distal muscle weakness and atrophy that affected the lower more than the upper extremities.
A subtype of autosomal dominant limb-girdle muscular dystrophy characterized by an adult-onset of slowly progressive, proximal pelvic girdle weakness, with none, or only minimal, shoulder girdle involvement, and absence of cardiac and respiratory symptoms. Mild to moderate elevated creatine kinase serum levels and gait abnormalities are frequently observed.
Asparagine synthetase deficiency is a condition that causes neurological problems in affected individuals starting soon after birth. Most people with this condition have an unusually small head size (microcephaly ) that worsens over time due to loss (atrophy) of brain tissue. They also have severe developmental delay that affects both mental and motor skills (psychomotor delay). Affected individuals cannot sit, crawl, or walk and are unable to communicate verbally or nonverbally. The few affected children who achieve developmental milestones often lose these skills over time (developmental regression).
A number sign (#) is used with this entry because of evidence that asparagine synthetase deficiency (ASNSD) is caused by homozygous or compound heterozygous mutation in the ASNS gene (108370) on chromosome 7q21. Description ASNS deficiency (ASNSD) is an autosomal recessive severe neurologic disorder characterized by microcephaly, severely delayed psychomotor development, progressive encephalopathy, cortical atrophy, and seizure or hyperekplexic activity. The disorder shows onset in utero or at birth and may result in early death (summary by Ruzzo et al., 2013). Clinical Features Ruzzo et al. (2013) reported 9 patients from 4 unrelated families with a similar phenotype characterized by congenital and progressive microcephaly (up to -7 SD), lack of or severely delayed psychomotor development, appendicular hypertonia and hyperreflexia, and decreased cerebral volume. Two families were Iranian Jewish, 1 was Bangladeshi, and 1 was French Canadian.
Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome is a rare, genetic, neurometabolic disorder characterized by severe, progressive microcephaly, severe to profound global development delay, intellectual disability, seizures (typically tonic and/or myoclonic and frequently intractable), hyperekplexia, and axial hypotonia with appendicular spasticity, as well as hyperreflexia, dyskinetic quadriplegia, and abnormal brain morphology (cerebral atrophy with variable additional features including ventriculomeglay, pons and/or cerebellar hypoplasia, simplified gyral pattern and delayed myelination). Cortical blindness, feeding difficulties and respiratory insufficiency may also be associated.
However, avoidance behaviour is reinforced through negative reinforcement . [5] [25] Wolpe developed a technique called systematic desensitization to help participants avoid "avoidance". [26] Research results have suggested that even with a decrease in therapeutic contact densensitization is still very effective. [27] However, other studies have shown that therapists play an essential role in acrophobia treatment. [28] Treatments like reinforced practice and self-efficacy treatments also emerged. [5] There have been a number of studies into using virtual reality therapy for acrophobia. [29] [30] Botella and colleagues [31] and Schneider [31] were the first to use VR in treatment. [5] Specifically, Schneider utilised inverted lenses in binoculars to "alter" the reality.
This combination was believed to alter these effects of Parkinson's Disease. [26] In the short term, this combination had brought positive results as behaviours of these patients had improved. [26] Yet these researchers found that in the long-term this combination provided a reverse effect, accelerating the cognitive slowing of the brain (bradyphrenia) and motor movement ( bradykinesia ). [26] H2 Antagonists [ edit ] H2 antagonists are a class of drugs that was found to provide positive outcomes throughout the treatment. [27] [28] Some studies showed that through oral admission, the H-2 antagonist will target specific receptors in the brain, by crossing the blood-brain barrier and will alter the rate of cognitive thought processing. [27] Psychiatrist Kaminski found that the improvement of this condition will create a positive correlation between the decrease of time in cognitive thought processing and the decrease in reaction time for tasks to be completed. [27] See also [ edit ] Sluggish cognitive tempo References [ edit ] ^ Blueprints Neurology, 2nd ed. [ page needed ] ^ a b c d e f g h i j Rogers, Daniel (9 July 2009).
