Food and Drug Administration. February 28, 2017 . Retrieved 1 March 2017 . ^ "Xermelo (telotristat ethyl) Tablets, for Oral Use. ... European Journal of Clinical Investigation . 28 (6): 431–40. doi : 10.1046/j.1365-2362.1998.00305.x .
Clinical Features Anderson (1966) observed appendiceal carcinoid in father and daughter. Eschbach and Rinaldo (1962) reported fatal malignant carcinoid of the ileum in brother and sister. Duodenal carcinoid occurs with multiple endocrine neoplasia (131100, 162300, 171400). Cytogenetics Karanjawala et al. (2000) reported the first account of an individual with apparently nonmosaic complete maternal isodisomy of chromosome 8. The individual was identified during routine genotyping in a genomewide search for type II diabetes susceptibility genes, although he did not have diabetes.
Choate et al. (2010) then analyzed 28 revertant spots from 5 additional patients. ... These observations confined the disease locus to an interval on 17q containing a gene cluster encoding 28 type 1 keratins and 24 keratin-associated proteins.
Ichthyosis with confetti is a disorder of the skin. Individuals with this condition are born with red, scaly skin all over the body, which can be itchy in some people. In childhood or adolescence, hundreds to thousands of small patches of normal skin appear, usually on the torso. The numerous pale spots surrounded by red skin look like confetti, giving the condition its name. The patches of normal skin increase in number and size over time. In addition to red, scaly skin, people with ichthyosis with confetti typically have abnormally thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Many affected individuals have excess hair (hirsutism) on some parts of the body, particularly on the arms and legs.
Ichthyosis en confetti Other names Ichthyosis with confetti , Congenital reticular ichthyosiform erythroderma and Ichthyosis variegata , [1] Ichthyosis with confetti is inherited in an autosomal dominant manner Specialty Dermatology Ichthyosis en confetti , is a very rare form of congenital ichthyosis in which healthy patches of normal skin co-exist within the abnormal skin areas. [2] The condition is caused by a frameshift mutation in the keratin 10 gene (KRT10); [3] mutant keratin 10 accumulates in the nucleolus, a sub-nuclear structure, rather than within cellular intermediate filaments like the wild-type protein. Children with the condition exhibit red, flaky skin; however, for reasons not yet totally clear, wild type clonal patches of skin start to appear, in place of the red, flaky skin. Due to the clonal nature of the growth of the normal skin cells, it appears the patient is covered with confetti, hence the name of the condition. [3] It has been hypothesized that this is the result of a combination of mitotic recombination and natural selection within the skin. [4] See also [ edit ] List of cutaneous conditions caused by mutations in keratins List of cutaneous conditions References [ edit ] ^ Krunic, A. L.; Palcesky, D.; Busbey, S.; Medenica, M. (2003). "Congenital reticular ichthyosiform erythroderma--ichthyosis variegata: a case report and review of the literature" . Acta Dermato-venereologica . 83 (1): 36–39. doi : 10.1080/00015550310002684 .
PMID 16235165 . ^ Sun, Lena (October 28, 2016). "New data shows a deadly measles complication is more common than thought" . The Washington Post . Retrieved October 28, 2016 . ^ Fisher DL, Defres S, Solomon T (2015).
Bartram et al. (1982) observed subacute sclerosing panencephalitis in a brother and sister of nonconsanguineous parents of 11 children living in rural Turkey. An interval of 4 years separated onset of symptoms in the 2 children. Fibroblast interferon had no beneficial effect. Neuro - Subacute sclerosing panencephalitis Inheritance - Autosomal recessive ▲ Close
A chronic progressive encephalitis that develops a few years after measles infection and presents with a demyelination of the cerebral cortex. Epidemiology Due to the measles immunization, nowadays cases of SSPE are very rare. In the United States, less than 10 cases/year are reported. However, in some countries like India, over 20 cases/per million people/per year are reported. Males are more often affected than females (3:1). Clinical description SSPE occurs primarily in children and young adults, approximately 2-8 years after the initial infection. Patients present with a history of measles infection (though the person seems to have fully recovered from the illness).
Subacute sclerosing panencephalitis (SSPE) a rare condition that is caused by a measles infection acquired earlier in life. Signs and symptoms of the condition primarily affect the central nervous system and often develop approximately 7 to 10 years after a person recovers from the measles. Affected people may initially experience behavioral changes, dementia, and disturbances in motor function. In the late stages of the disease, affected people often progress to a comatose state, and then to a persistent vegetative state. Ultimately, many people with SSPE succumb to fever, heart failure, or the brain's inability to continue controlling the autonomic nervous system .
. ^ Tossa, Paul; Deloge-Abarkan, Magali; Zmirou-Navier, Denis; Hartemann, Philippe; Mathieu, Laurence (28 April 2006). "Pontiac fever: an operational definition for epidemiological studies" . ... M.; GRAHAM, F.; SCHOUSBOE, M.; SYKES, K. (28 September 2009). "AAn outbreak of Pontiac fever due to Legionella longbeachae serogroup 2 found in potting mix in a horticultural nursery in New Zealand".
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.
Other features during the neonatal period included hypotonia (58%), transient tachypnea of the newborn (47%), poor sucking (44%), tremor (28%), and hypoglycemia (17%). There were mild craniofacial features such as prominent forehead, midfacial hypoplasia, wide nasal bridge, hypertelorism, hirsutism, and arched eyebrows. ... Population Genetics In the French Canadian population of the Saguenay-Lac-Saint-Jean region of Quebec province, De Braekeleer (1991) estimated the prevalence at birth of cytochrome c oxidase deficiency to be 1 in 2,473, giving a carrier frequency of 1 in 28. Morin et al. (1993) estimated the incidence of LSFC at 1 in 2,063 live births between 1979 and 1990, giving a carrier rate of 1 in 23 among inhabitants of the SLSJ region.
Saguenay-Lac-St. Jean (SLSJ) type congenital lactic acidosis, a French Canadian form of Leigh syndrome (see this term), is a mitochondrial disease characterized by chronic metabolic acidosis, hypotonia, facial dysmorphism and delayed development. Epidemiology The exact prevalence of this disorder is not known. It was first described in Saguenay-Lac-Saint-Jean (Quebec, Canada) where its prevalence at birth is estimated to be 1/2,000. In this region, the prevalence of the gene mutation underlying the disorder is estimated to be 1/23 inhabitants, and may be due to a founder effect. Clinical description Facial dysmorphism is characterized by a prominent forehead, wide nasal bridge, hypertelorism, broad anterior fontanelle, midfacial hypoplasia, broad midline, synophrys, and a characteristic arched form of the eyebrows, along with mild hirsutism. There are 3 forms of the disease corresponding to varying degrees of severity: a neonatal form, a classic form and a so-called "survivor" form.
In addition to previously described mutations in TP53 (191170), CDKN2A (600160), PIK3CA (171834), and HRAS (171834), Agrawal et al. (2011) identified mutations in NOTCH1 (190198). Nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type. ... Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumors with favorable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8 (601763), NOTCH1, and TP53.
A rare head and neck tumor characterized by a malignant epithelial neoplasm with evidence of squamous differentiation, most commonly located in the piriform sinus, less frequently the posterior pharyngeal wall or the postcricoid area. The tumor can spread directly to adjacent structures or metastasize via lymphatic and blood vessels to regional lymph nodes, or lung, liver, and bones, respectively. Primary risk factors are tobacco smoking and (to a lesser extent) alcohol consumption. Patients may present with odynophagia, dysphagia, signs and symptoms related to a neck mass, voice changes, otalgia, and constitutional symptoms.
A rare head and neck tumor characterized by a firm infiltrative neoplasm with squamous differentiation, arising from the mucosal epithelium, and most commonly located in the tongue, floor of the mouth, or gingiva, but also the buccal mucosa or any other area of the oral cavity, depending on prevailing risk factors (such as smoking, alcohol consumption, and tobacco chewing). Patients present with a variably white, erythematous, mixed, nodular, or ulcerated lesion, which may cause discomfort, pain, or reduced mobility of the tongue. The tumor is aggressive with a propensity for local invasion and early lymph node metastasis.
Squamous cell carcinoma is a cancer that arises from particular cells called squamous cells. Squamous cells are found in the outer layer of skin and in the mucous membranes, which are the moist tissues that line body cavities such as the airways and intestines. Head and neck squamous cell carcinoma (HNSCC) develops in the mucous membranes of the mouth, nose, and throat. HNSCC is classified by its location: it can occur in the mouth (oral cavity), the middle part of the throat near the mouth (oropharynx), the space behind the nose (nasal cavity and paranasal sinuses), the upper part of the throat near the nasal cavity (nasopharynx), the voicebox (larynx), or the lower part of the throat near the larynx (hypopharynx). Depending on the location, the cancer can cause abnormal patches or open sores (ulcers) in the mouth and throat, unusual bleeding or pain in the mouth, sinus congestion that does not clear, sore throat, earache, pain when swallowing or difficulty swallowing, a hoarse voice, difficulty breathing, or enlarged lymph nodes.
A rare head and neck tumor characterized by a malignant epithelial neoplasm with evidence of squamous differentiation, most commonly located in the supraglottis or glottis. The tumor can spread directly to adjacent structures or metastasize via lymphatic and blood vessels to regional lymph nodes, or lung, liver, and bones, respectively. Primary risk factors are tobacco smoking and (to a lesser extent) alcohol consumption. Patients may present with hoarseness, dyspnea, stridor, dysphagia, hemoptysis, or odynophagia.
A rare head and neck tumor characterized by a malignant epithelial neoplasm with evidence of squamous differentiation, which may arise in association with high-risk HPV in a subset of cases. HPV-positive tumors have a strong predilection for the base of tongue and the palatine tonsils and typically present at an advanced clinical stage with cervical lymphadenopathy. They are associated with significantly better prognosis than HPV-negative tumors, which more commonly involve the soft palate, manifest as sore throat and difficulty in swallowing or a neck mass, and occur in older patients. Smoking and alcohol consumption are important risk factors.
A rare head and neck tumor characterized by a malignant epithelial neoplasm most commonly arising in the maxillary sinus or nasal cavity, occurring as a keratinizing, a non-keratinizing, or a spindle cell (sarcomatoid) type. Patients may present with nasal obstruction, epistaxis, rhinorrhea, swelling, or (at more advances stages) with facial pain and/or paralysis, diplopia, and proptosis. Patients with paranasal sinus tumors present later and at a higher stage than patients with nasal cavity carcinomas. Risk factors are smoking and industrial exposures. High-risk HPV is most frequently associated with the non-keratinizing type.
A rare head and neck tumor characterized by a firm infiltrative neoplasm with squamous differentiation, most commonly arising at the vermilion border of the lower lip. Patients present with a usually asymptomatic lesion of variable appearance, such as ulceration, a focus of whitish thickening, a dry atrophic area, or an area of persistent chapping and localized flaking and crusting. Carcinomas of the lower lip tend to progress slowly (as opposed to those of the upper lip). Invasion of adjacent structures, including perineural spread, is typical, with a variable rate of metastasis, depending on the location.
A rare cerebellar malformation characterized by congenital complete or partial fusion of the cerebellar hemispheres, dentate nuclei, and middle cerebellar peduncles, and complete or partial absence of the vermis. It may occur as an isolated anomaly or together with other malformations of the brain and is associated with variable clinical manifestations including developmental delay, ataxia, dysarthria, oculomotor abnormalities, seizures, and involuntary head movements, among others. Epidemiology The exact prevalence is unknown. A value of 4 in 3000 paediatric magnetic resonance imaging (MRI) scans was reported in one study and around 50 cases have been reported in the literature. Clinical description Other cerebral anomalies often associated with RS include fusion of the dentate nuclei, deformation of the fourth ventricle, and fusion of the cerebral peduncles. Supratentorial findings include hydrocephalus, fusion of the thalami, anomalies of the corpus callosum and septo-optic dysplasia.
Glaucoma-ectopia-microspherophakia-stiff joints-short stature syndrome is characterized by progressive joint stiffness, glaucoma, short stature and lens dislocation. It has been described in three members of a family (the grandfather, his daughter and grandson). It is likely to be transmitted as an autosomal dominant trait. The acronym GEMSS (Glaucoma, Ectopia, Microspherophakia, Stiff joints, Short stature) was proposed as a name for the syndrome. This syndrome shows similarities to Moore-Federman syndrome (see this term).
Among 58 blood relatives of the index case, 28 were diagnosed with early CAD, defined as MI, angina, or sudden cardiac death at or before age 50 in men or 55 in women.
A C-to-T SNP at chromosome 1 position 160300514 (rs12143842, T allele frequency = 24%) was associated with a QT interval duration increase of 4.4 ms per additional T allele (P = 4.4 x 10(-28)). For comparison, the most strongly associated variant to that time, rs10494366, was associated with a 3.5-ms increase (P = 1.6 x 10(-23)) per additional G allele.
Ben Khelifa et al. (2011) studied 2 infertile brothers of Tunisian descent who both had nearly 100% large-headed spermatozoa that were 28 to 52% multiflagellate, with sperm counts of 0.8 to 0.9 x 10(6) per ml.
Macrozoospermia is a condition that affects only males. It is characterized by abnormal sperm and leads to an inability to father biological children (infertility). In affected males, almost all sperm cells have abnormally large and misshapen heads. The head of the sperm cell contains the male's genetic information that is to be passed on to the next generation. Normally, the head of a sperm cell contains one copy of each chromosome . In men with macrozoospermia, the sperm cell head contains extra chromosomes, usually four copies of each instead of the usual one.
Male infertility due to large-headed multiflagellar polypoid spermatozoa is a male infertility due to sperm disorder characterized by the presence, in sperm, of a very high percentage of spermatozoa with enlarged head, irregular head shape, multiple flagella, and abnormal midpiece and acrosome. It is generally associated with severe oligoasthenozoospermia and a high rate of sperm chromosomal abnormalities (polyploidy, aneuploidy).
Gambelunghe et al. (1999) evaluated the association of APS2-Addison disease with both MICA and MICB gene polymorphism 28 autoimmune (21-hydroxylase autoantibody-positive) Addison disease patients and in 75 healthy subjects from central Italy.
A chronic and rare endocrine disorder due to autoimmune destruction of the adrenal cortex and resulting in a glucocorticoid and mineralocorticoid deficiency. Properly speaking, it designates autoimmune adrenalitis, but it is a term commonly used to describe any form of chronic primary adrenal insufficiency (CPAI). Epidemiology The prevalence of AD is 1/9,000-1/6,900 in the developed countries. Clinical description Disease onset peaks around 40 but it can occur at any age. It presents insidiously with nonspecific symptoms that can be mistaken for other more prevalent conditions.
If aldosterone is deficient, maintenance therapy also includes oral doses of fludrocortisone acetate. [28] Prognosis [ edit ] Outcomes are typically good when treated. ... National Endocrine and Metabolic Diseases Information Service. Archived from the original on 28 October 2007 . Retrieved 26 October 2007 . ^ Freeman, Lynette K.; Chanco Turner, Maria L. (2006). ... Archived from the original on 5 September 2015. ^ White, Katherine (28 July 2004). "What to do in an emergency -Addisonian crisis" .
Chronic primary adrenal insufficiency (CPAI) is a chronic disorder of the adrenal cortex resulting in the inadequate production of glucocorticoid and mineralocorticoid hormones. Epidemiology It is a rare disease with a prevalence of about 1/ 7, 100 and an annual incidence of about 1/ 250, 000 in Western populations. Clinical description Disease onset peaks around 40 but can occur at any age. It presents insidiously with nonspecific symptoms that can be mistaken for other more prevalent conditions. Common manifestations include fatigue, loss of energy, malaise, weight loss, nausea, anorexia (failure to thrive in children), muscle and joint pain.
Chuandi et al. (1985) reported a Chinese kindred in which persons in 3 generations, and by implication at least 1 person in a fourth earlier generation, had chronic adrenal insufficiency. This was manifest by hyperpigmentation, hypernatriuria, hypokaliuria, and decreased plasma total cortisol and urine free cortisol; PTC, UFC and 17-OHCS did not respond to ACTH stimulation. Eleven affected persons in 5 sibships were identified, including several instances of male-to-male transmission. Endocrine - Chronic adrenal insufficiency Inheritance - Autosomal dominant Lab - Hypernatriuria - Hypokaliuria - Decreased plasma total cortisol - Decreased urine free cortisol - No response of PTC, UFC and 17-OHCS to ACTH stimulation Skin - Hyperpigmentation ▲ Close
Addison's disease occurs when the adrenal glands do not produce enough (or any) of the hormones, cortisol and aldosterone. These adrenal gland hormones are necessary for balancing water and energy in the body. Symptoms usually develop slowly over time, and may include fatigue, loss of appetite, abdominal pain, and dark patches of skin. Sometimes symptoms occur suddenly causing a life-threatening condition called acute adrenal failure, also known as an acute adrenal crisis. Symptoms of an acute adrenal crisis include sudden weakness, pain, and fainting.
Overview Addison's disease, also called adrenal insufficiency, is an uncommon illness that occurs when the body doesn't make enough of certain hormones. In Addison's disease, the adrenal glands make too little cortisol and, often, too little of another hormone, aldosterone. Addison's disease can affect anyone and can be life-threatening. Treatment involves taking hormones to replace those that are missing. Symptoms Addison's disease symptoms usually happen slowly, often over months. The disease can move so slowly that people who have it may ignore the symptoms at first.
Congenital factor V deficiency is an inherited bleeding disorder due to reduced plasma levels of factor V (FV) and characterized by mild to severe bleeding symptoms. Epidemiology Prevalence of homozygous forms is estimated at 1/1,000,000. Both sexes are equally affected. Clinical description Congenital FV deficiency can manifest at any age, with the most severe forms manifesting early in life. Common clinical signs include epistaxis, bruising, mucosal bleeding, soft tissue bleeding, and hemarthrosis. Excessive and prolonged bleeding during or following surgery, delivery or trauma are frequent.
Factor V deficiency is an inherited bleeding disorder that prevents blood clots from forming properly. This disorder is caused by mutations in the F5 gene, which leads to a deficiency of a protein called coagulation factor V. The reduced amount of factor V may lead to nosebleeds, easy bruising, and excessive bleeding following surgery or trauma. This condition is inherited in an autosomal recessive manner. Treatment includes fresh blood plasma or fresh frozen plasma infusions during bleeding episodes. This condition should not be confused with Factor V Leiden thrombophilia , a genetic risk factor for blood clots.
Factor V deficiency is a rare bleeding disorder. The signs and symptoms of this condition can begin at any age, although the most severe cases are apparent in childhood. Factor V deficiency commonly causes nosebleeds; easy bruising; bleeding under the skin; bleeding of the gums; and prolonged or excessive bleeding following surgery, trauma, or childbirth. Women with factor V deficiency can have heavy or prolonged menstrual bleeding (menorrhagia). Bleeding into joint spaces (hemarthrosis) can also occur, although it is rare. Severely affected individuals have an increased risk of bleeding inside the skull (intracranial hemorrhage), in the lungs (pulmonary hemorrhage), or in the gastrointestinal tract , which can be life-threatening.
"Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency". Nat. Genet . 28 (1): 73–6. doi : 10.1038/88299 . PMID 11326280 .
Leukocyte adhesion deficiency type II (LAD-II) is a form of LAD (see this term) characterized by recurrent bacterial infections, severe growth delay and severe intellectual deficit. Epidemiology LAD-II is extremely rare: less than 10 cases have been reported so far. Clinical description The first signs usually occur in infancy or early childhood. Patients present recurrent bacterial infections, severe growth delay resulting in short stature, and severe intellectual deficit. Patients have the Bombay phenotype (they do not express the H antigen).
All affected individuals reported repeated episodes of unilateral keratoendotheliitis, occurring from 1 to 6 times per year, starting at the median age of 11 years (range, 5-28 years). Episodes became milder in middle age, and their frequency decreased; there was no apparent seasonal variation.
Contents 1 Presentation 2 Genetics 3 Diagnosis 4 Treatment 5 Prognosis 6 History 7 References 8 External links Presentation [ edit ] Patients experience repeated unilateral attacks of keratitis 1 to 6 times per year, beginning at the age of 5 to 28 years. Men and women are equally affected.
In both cases, the giant mononucleate erythroblasts and the multinucleate erythroblasts had total DNA contents up to 28 and 48 times, respectively, the haploid DNA content.
Congenital dyserythropoietic anemia type III (CDA III) is a rare form of CDA (see this term) characterized by dyserythropoiesis, with big multinucleated erythroblasts in the bone marrow, and manifesting with mild to moderate anemia. Epidemiology The prevalence is unknown. Three families have been reported with autosomal dominant CDA III in Sweden, America and Argentina. Other sporadic CDA III-like cases have been described. In total, about 60 cases have been reported worldwide. Clinical description The clinical presentation is variable. CDA III can manifest with mild anemia and jaundice in neonates but it may not be discovered until childhood or adulthood. Intensity of symptoms increases during infections, following trauma, and during pregnancy.
Congenital dyserythropoietic anemia type III Specialty Hematology Congenital dyserythropoietic anemia type III ( CDA III ) is a rare autosomal dominant disorder characterized by macrocytic anemia , bone marrow erythroid hyperplasia and giant multinucleate erythroblasts . [1] New evidence suggests that this may be passed on recessively as well. Contents 1 Presentation 2 Genetics 3 Diagnosis 4 Treatment 5 See also 6 References 7 Further reading 8 External links Presentation [ edit ] The signs and symptoms of CDA type III tend to be milder than those of the other types. Most affected individuals do not have hepatosplenomegaly, and iron does not build up in tissues and organs. In adulthood, abnormalities of a specialized tissue at the back of the eye (the retina) can cause vision impairment. Some people with CDA type III also have a blood disorder known as monoclonal gammopathy, which can lead to a cancer of white blood cells (multiple myeloma). [2] Genetics [ edit ] CDA type III is transmitted autosomal dominantly.
