Overview Peritonitis is a serious condition that starts in the abdomen. That's the area of the body between the chest and the pelvis. Peritonitis happens when the thin layer of tissue inside the abdomen becomes inflamed. The tissue layer is called the peritoneum. Peritonitis usually happens due to an infection from bacteria or fungi. There are two types of peritonitis: Spontaneous bacterial peritonitis. This infection is caused by bacteria. It can happen when someone has liver disease, such as cirrhosis, or kidney disease.
"Analysis of Clinical Presentations of Bruton Disease: A Review of 20 Years of Accumulated Data from Pediatric Patients at Severance Hospital" . Yonsei Medical Journal . 49 (1): 28–36. doi : 10.3349/ymj.2008.49.1.28 .
Airborne powders of any sort can irritate lung tissue, and powders made from starchy plants (corn, arrowroot) provide food for fungi and are not recommended by the American Academy of Dermatology. [28] Antifungals [ edit ] In persistent or especially bad rashes, an antifungal cream often has to be used.
Overview Diaper rash is a common form of irritated skin (dermatitis) that looks like patches of inflamed skin on your baby's bottom. It's often related to wet or infrequently changed diapers, skin sensitivity, and chafing. It usually affects babies, though anyone who wears a diaper regularly can develop the condition. Diaper rash usually clears up with simple at-home treatments, such as air drying, more-frequent diaper changes and ointment. Symptoms Signs and symptoms of diaper rash include: Inflamed skin in the diaper area — buttocks, thighs and genitals Itchy, tender skin in the diaper area Sores in the diaper area Discomfort, fussiness or crying, especially during diaper changes When to see a doctor If your baby's skin doesn't improve after a few days of home treatment, talk with your health care provider.
The accumulation of iron in tissues due to impaired iron export can lead to increasing transferrin iron saturation and liver parenchymal iron overload in advanced stages of the disease. [24] More ferritin is produced to suppress oxidative cell damage, although the amount of ferritin that cells can accumulate is limited. [25] Hemochromatosis type 4B is characterized by abnormal iron release from macrophages and enterocytes because the mutant ferroportin is resistant to the hepcidin protein, which serves a regulatory function in wild-type ferroportin. [26] Intestinal iron absorption and release of iron from macrophages is increased. [27] Thus, this form of the disease leads to elevated transferrin saturation levels. [28] Systemic iron overload results, and liver iron deposition is primarily in the hepatocytes. [29] Diagnosis [ edit ] Diagnosis is based upon identification of symptoms, medical history, family history, and laboratory tests.
Hemochromatosis type 4 (also called ferroportin disease) is a disease in which too much iron builds up in the body. This is also called iron overload. Accumulation of iron in the organs is toxic and can cause organ damage. While many organs can be affected, iron overload is especially likely to affect the liver, heart , and pancreas . Hemochromatosis type 4 can be further divided into two subtypes: Hemochromatosis type 4A Hemochromatosis type 4B People with hemochromatosis type 4A might not have any symptoms of the disease. Other individuals may develop liver disease as they get older. Hemochromatosis type 4B can be associated with fatigue , weakness, and joint pain .
A number sign (#) is used with this entry because hemochromatosis type 4 (HFE4) is caused by heterozygous mutation in the SLC40A1 gene (604653), which encodes ferroportin, on chromosome 2q32. For general background information and a discussion of genetic heterogeneity of hereditary hemochromatosis, see 235200. Clinical Features Pietrangelo et al. (1999) described an Italian family with an autosomal dominant form of hemochromatosis not associated with mutations in the HFE gene (613609) and not linked to 6p. Fifteen members of this pedigree suffered from iron overload resulting in hepatic fibrosis, diabetes, impotence, and arrhythmias. In addition to autosomal dominant inheritance, features distinguishing this entity from classic hemochromatosis included early iron accumulation in reticuloendothelial cells and a marked increase in serum ferritin prior to elevation of the transferrin saturation.
Hemochromatosis type 4 (also called ferroportin disease) is a form of rare hereditary hemochromatosis (HH; see this term), a group of diseases characterized by excessive tissue iron deposition of genetic origin. Epidemiology HH type 4 is less rare than the other rare forms of HH, hemochromatosis type 2 or type 3 (see these terms). Fewer than 200 cases have been reported in the literature. It has a worldwide distribution. Clinical description The disease is phenotypically heterogeneous with two sub-types. Ferroportin disease form A is the usual form and is generally asymptomatic with no tissue damage and further complications.
Description The most basic description of Moebius syndrome is a congenital facial palsy with impairment of ocular abduction. The facial nerve (cranial nerve VII) and abducens nerve (CN VI) are most frequently involved, but other cranial nerves may be involved as well. Other variable features include orofacial dysmorphism and limb malformations. Mental retardation has been reported in a subset of patients. Most cases of Moebius syndrome are sporadic, but familial occurrence has been reported (Verzijl et al., 2003). The definition of and diagnostic criteria for Moebius syndrome have been controversial and problematic.
Moebius syndrome is a rare neurological condition that primarily affects the muscles that control facial expression and eye movement. Signs and symptoms of the condition may include weakness or paralysis of the facial muscles; feeding, swallowing, and choking problems; excessive drooling; crossed eyes; lack of facial expression; eye sensitivity; high or cleft palate; hearing problems; dental abnormalities; bone abnormalities in the hands and feet; and/or speech difficulties. Affected children often experience delayed development of motor skills (such as crawling and walking), although most eventually acquire these skills. Moebius syndrome is caused by the absence or underdevelopment of the 6th and 7th cranial nerves , which control eye movement and facial expression. Other cranial nerves may also be affected. There is no cure for Moebius syndrome, but proper care and treatment give many individuals a normal life expectancy.
Transient transfection of liver cells with a reporter gene construct containing the CETP promoter from nucleotides -1707 to +28 revealed that the -1337T allele was expressed to a significantly lower degree (34%, P less than 0.0001) than the -1337C allele.
A number sign (#) is used with this entry because apolipoprotein C-III deficiency is caused by heterozygous mutation in the APOC3 gene (107720) on chromosome 11q23. For a discussion of phenotypic features and genetic heterogeneity of hyperalphalipoproteinemia, see HALP1 (143470). Molecular Genetics In a family with hyperalphalipoproteinemia, von Eckardstein et al. (1991) identified a heterozygous carrier of an apolipoprotein C-III variant (107720.0002) by the presence of additional bands after isoelectric focusing (IEF) of very low density lipoprotein (VLDL). Two variant carriers exhibited plasma concentrations of HDL cholesterol and APOA1 (107680) above the 95th percentile for sex-matched controls. Their plasma concentrations of apoC-III were 30 to 40% lower than those of 2 unaffected family members and random controls.
Braces may be especially effective when only one knee is affected. [1] Shoe insoles that are fitted to correct flat feet provide significant relief to those with severely flat feet. [27] However, it has been found that insoles used to correct medial knee osteoarthritis (the more common form) may not offer much pain relief. [28] [29] Lifestyle [ edit ] Body weight [ edit ] Obesity is a known and very significant risk factor for the development of osteoarthritis. [9] Furthermore, losing weight reduces mechanical stress acting upon the knees when standing, possibly reducing pain and improving function in knee osteoarthritis. [26] [1] However, it is necessary to ascertain whether the patient is actually overweight before committing to weight loss as a management technique. [9] Exercise [ edit ] Exercises can help increase range of motion and flexibility as well as help strengthen the muscles in the leg. [30] Physical therapy and exercise are often effective in reducing pain and improving function.
"ATGL/CGI-58-Dependent Hydrolysis of a Lipid Storage Pool in Murine Enterocytes" . Cell Reports . 28 (7): 1923–1934.e4. doi : 10.1016/j.celrep.2019.07.030 .
Cerebral creatine deficiency Other names CCD Specialty Pediatrics , medical genetics , neurology Symptoms intellectual disability, developmental delay, seziures Usual onset early childhood Causes Genetic Diagnostic method Blood, and urine tests, genetic testing , brain MRS Treatment dietary modification, creatine supplementation Prognosis variable; early treatment for AGAT and GAMT deficiency results in significantly improved outcomes Cerebral creatine deficiencies are a small group of inherited disorders that result from defects in creatine biosynthesis and utilization. Commonly affected tissues include the brain and muscles. There are three distinct CCDs. The most common is creatine transporter defect (CTD), an X-linked disorder caused by pathogenic variants in SLC6A8 . The main symptoms of CTD are intellectual disability and developmental delay, and these are caused by a lack of creatine in the brain, due to the defective transporter. There are also two enzymatic defects of creatine biosynthesis, arginine:glycine amidinotransferase deficiency (AGAT deficiency), caused by variants in GATM and guanidinoacetate methyltransferase deficiency (GAMT deficiency), caused by variants in GAMT .
Chanarin-Dorfman syndrome is a condition in which fats (lipids) are stored abnormally in the body. Affected individuals cannot break down certain fats called triglycerides, and these fats accumulate in organs and tissues, including skin, liver, muscles, intestine, eyes, and ears. People with this condition also have dry, scaly skin (ichthyosis), which is usually present at birth. Additional features of this condition include an enlarged liver (hepatomegaly), clouding of the lens of the eyes (cataracts ), difficulty with coordinating movements (ataxia), hearing loss, short stature, muscle weakness (myopathy), involuntary movement of the eyes (nystagmus), and mild intellectual disability. The signs and symptoms vary greatly among individuals with Chanarin-Dorfman syndrome.
Neutral lipid storage disease (NLSD) refers to a group of diseases characterized by a deficit in the degradation of cytoplasmic triglycerides and their accumulation in cytoplasmic lipid vacuoles in most tissues of the body. The group is heterogeneous: currently cases of NLSD with icthyosis (NLSDI/Dorfman-Chanarin disease; see this term) and NLSD with myopathy (NLSDM/neutral lipid storage myopathy; see this term) can be distinguished. Epidemiology The group of diseases is very rare and the prevalence is unknown (around 50 cases have been reported in medical literature, of which 3 had NLSDM) because of the vagueness of the descriptions. Clinical description In NLSDI, generalized ichthyosis occurs in 95% of cases, moderate myopathic syndrome (or abnormal serum muscle enzyme levels), intellectual deficit and moderate hepatomegaly (or functional impairment of the liver) occur in 60% of cases, ocular (cataract, retinopathy) and hearing abnormalities (deafness) occur in 40% of cases, and neuropathy and short stature occur in 20% of cases. Etiology NLSDI/Dorfman-Chanarin disease is caused by mutations in the ABHD5 gene (3p21), NLSDM by mutations in the PNPLA2/ATGL gene (localized to 11p15.5).
A form of neutral lipid storage disease characterized by the accumulation of lipid vacuoles in leukocytes (so-called Jordan's anomaly seen in peripheral blood smears) and a variety of other cell types. The clinical picture consists of congenital ichthyosis of the congenital ichthyosiform erythroderma type together with variable multisystem involvement. Manifestations include hepatosplenomegaly, myopathy, intestinal disease, growth retardation, cataracts, sensorineural hearing loss, and intellectual disability, among others.
A number sign (#) is used with this entry because Chanarin-Dorfman syndrome, a rare form of nonbullous congenital ichthyosiform erythroderma (NCIE; see 242300), can be caused by homozygous mutation in the CGI58 gene (ABHD5; 604780). Another form of neutral lipid storage disease without ichthyosis but with myopathy (NLSDM; 610717) is caused by mutation in the PNPLA2 gene (609059). Clinical Features In a 5-year-old girl, Angelini et al. (1980) identified a syndrome, presumably inherited as an autosomal recessive, characterized by congenital ichthyosis, hepatosplenomegaly, vacuolated granulocytes (Jordans anomaly), and myopathy. Pathologic, ultrastructural and biochemical studies showed nonlysosomal, multisystem triglyceride storage. Cultured fibroblasts showed an increased uptake but decreased oxidation of labeled oleate.
Chanarin-Dorfman syndrome is an inherited condition in which fats are stored abnormally in the body. Affected individuals cannot break down certain fats called triglycerides . These fats accumulate in organs and tissues, including skin, liver, muscles, intestine, eyes, and ears. At birth, affected individuals usually present with dry, scaly skin. Additional features include an enlarged liver, cataracts, difficulty with coordinating movements (ataxia), hearing loss, short stature, muscle weakness, nystagmus, and mild intellectual disability. The signs and symptoms vary greatly among individuals with this condition.
Certain mutations on the CUBN or AMN (genes that encode cubilin and amnionless respectively) have been identified through genetic analysis, and ethnic susceptibility of some of the mutations were indicated from the current research. [2] [3] It has been further suggested that mutations on CUBN were restricted to exon 1-28 which encoded amnionless binding domains (EGF) and IF-Cbl binding region of cubilin, while AMN mutations primarily clustered in intron 8-11 and transmembrane domain in exon 10. [2] Some interesting aspects of particular mutations were also elucidated by the researchers, for example, CUBN mutation c.3890C>T; p.Pro1297Leu, was considered to be a Finnish founder mutation presenting mostly in homozygous status, while an AMN mutation c.208-2A>G, which was thought to account for 15% IGS cases around the world, was postulated as an ancient founder mutation that can trace back to approximately 13,600 years ago. [2] [4] Pathogenesis [ edit ] Vitamin B 12 , is an essential water-soluble vitamin found in animal products (such as liver, meat, fish, and dairy products). [5] Vitamin B 12 is not found in plant sources; a vegetarian diet can be a risk factor for vitamin B 12 deficiency.
A number sign (#) is used with this entry because of evidence that hereditary megaloblastic anemia-1 can be caused by mutation in the gene encoding cubilin (CUBN; 602997) or the AMN (605799) gene. The CUBN and AMN gene products form a complex that acts as a receptor for vitamin B12 and gastric intrinsic factor (GIF; 609342). Imerslund-Grasbeck syndrome was described by Imerslund (1960) in Norway and Grasbeck et al. (1960) in Finland; the Finnish cases were found to be due to mutations in cubilin, whereas the Norwegian cases were found to be due to mutations in AMN. Description Imerslund-Grasbeck syndrome is a form of congenital megaloblastic anemia due to vitamin B12 deficiency caused by a defect in the vitamin B12/intrinsic factor receptor. See also congenital pernicious anemia due to a defect in intrinsic factor (261000).
Imerslund-Grasbeck syndrome (IGS) or selective vitamin B12 (cobalamin) malabsorption with proteinuria is a rare autosomal recessive disorder characterized by vitamin B12 deficiency commonly resulting in megaloblastic anemia, which is responsive to parenteral vitamin B12 therapy and appears in childhood. Epidemiology The syndrome was first described in Finland and Norway where the prevalence is about 1/200 000. Clinical description Other manifestations include failure to thrive and grow, infections and neurological damage. Mild proteinuria (with no signs of kidney disease) is present in about half of the patients. Anatomical anomalies in the urinary tract were observed in some Norwegian patients.
Imerslund-Grasbeck syndrome (IGS) is a rare condition characterized by vitamin B12 deficiency , often causing megaloblastic anemia . IGS usually appears in childhood. Other features may include failure to thrive , infections, and neurological damage. Mild proteinuria (with no signs of kidney disease) is present in about half of affected individuals. IGS is caused by mutations in either the CUBN or AMN gene and is inherited in an autosomal recessive manner. Treatment includes life-long vitamin B12 injections, with which affected individuals can stay healthy for decades.
Bilateral frontoparietal polymicrogyria (BFPP) is a sub-type of polymicrogyria (PMG; see this term), a cerebral cortical malformation characterized by excessive cortical folding and abnormal cortical layering, that involves the frontoparietal region of the brain and that presents with hypotonia, developmental delay, moderate to severe intellectual disability, pyramidal signs, epileptic seizures, non progressive cerebellar ataxia, dysconjugate gaze and/or strabismus.
A number sign (#) is used with this entry because bilateral frontoparietal polymicrogyria (BFPP) is caused by homozygous mutation in the ADGRG1 gene (604110) on chromosome 16q21. Mutation in a cis-regulatory region of ADGRG1 causes bilateral perisylvian polymicrogyria (BPPR; 615752). See also unilateral polymicrogyria (610031). Clinical Features In 2 sisters, aged 7 and 10 years, Harbord et al. (1990) described developmental delay and a nonprogressive cerebellar ataxia with similar neurophysiologic and neuroradiologic findings of an extensive neuronal migration defect. There were no dysmorphic features, metabolic abnormalities, chromosomal defects or evidence of prenatal environmental toxins. Harbord et al. (1990) considered that these sibs had an autosomal recessive neuronal migration defect that had not previously been recorded.
Bilateral frontoparietal polymicrogyria (BFPP) is a rare neurological disorder that affects the cerebral cortex (the outer surface of the brain). BFPP specifically affects the frontal and parietal lobes on both sides of the brain (bilateral). Signs and symptoms typically include moderate to severe intellectual disability, developmental delay, seizures, cerebellar ataxia , strabismus, and dysconjugate gaze (eyes that are not aligned). Some cases are caused by mutations in the GPR56 gene and are inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person.
Extramammary Paget disease (EMPD) is characterized by a chronic eczema -like rash of the skin around the genital regions of males and females. Under the microscope, this condition looks very similar to a condition that occurs on the breast called mammary Paget disease . The primary difference between the two is the location of the rash. While the location of the rash for individuals with mammary Paget disease is around the nipple and areolar skin, EMPD may occur in the vulva, perianal region, scrotum, penis, and axilla. EMPD most often occurs in women between age 50 to 60. About 25 percent of extramammary Paget disease is associated with an underlying cancer. Treatment typically includes surgery. Prognosis varies depending on how early the disorder was diagnosed and treated as well as the association with an underlying cancer.
A rare skin tumor characterized by predominantly intraepithelial growth of an adenocarcinoma which may either arise primarily in the skin (primary extramammary Paget disease) or result from intraepithelial spread of a visceral carcinoma (secondary extramammary Paget disease). The lesion is typically located in the anogenital region, presenting as a scaly, oozing, pruritic or painful erythematous plaque often resembling eczema. It may exhibit an invasive component with a significant risk of lymph node metastasis.
Extramammary Paget disease is a cancerous disease seen at various sites, most often in the anogenital region. The clinical features are usually those of eczematous eruptions with weeping and crust formation. This disease has been shown to be a skin manifestation of internal malignancy. In a study of 40 patients with Paget disease of the anogenital region, Helwig and Graham (1963) did not find a family history of the disease in any of the cases. Kuehn et al. (1973) described a case occurring in a father and son. The father, aged 66, presented with extramammary Paget disease in the right scrotal area.
Folster-Holst et al. (1999) described a 28-year-old woman with characteristic clinical signs of Netherton syndrome in which human papillomaviruses were identified in papillomatous skin lesions and plane warts.
Netherton disease is a rare disorder affecting the skin, hair and immune system. Symptoms are present at birth and include red, scaly skin. Other symptoms include outbreaks of red, circular scaly rashes, thin, fragile hair (bamboo hair), and immune reactions such as hay fever, asthma, itchy skin, and eczema. Dehydration and infection are common and can be serious. Babies tend to grow slowly and have poor weight gain. Netherton syndrome is caused by the SPINK5 gene not working correctly. It is inherited in an autosomal recessive pattern. Netherton syndrome is diagnosed based on clinical examination, the symptoms, and genetic testing.
Ichthyosis linearis circumflexa Specialty Dermatology Ichthyosis linearis circumflexa is a distinctive skin condition of generalized hyperkeratosis and polycyclic and serpiginous erythematous plaques with a characteristic, migratory, double-edged scale at the margins, and is the typical cutaneous manifestation of Netherton's syndrome . [1] : 496 [2] : 563 See also [ edit ] Ichthyosis prematurity syndrome List of cutaneous conditions References [ edit ] ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine . (6th ed.). McGraw-Hill. ISBN 0-07-138076-0 . ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology . (10th ed.). Saunders. ISBN 0-7216-2921-0 . This Genodermatoses article is a stub . You can help Wikipedia by expanding it . v t e
Netherton syndrome (NS) is a skin disorder characterized by congenital ichthyosiform erythroderma (CIE), a distinctive hair shaft defect (trichorrhexis invaginata; TI) and atopic manifestations. Epidemiology Incidence is estimated at 1/200,000 births. Clinical description Patients generally present at birth with generalized erythroderma and scaling, and failure to thrive. Frequent complications include hypernatremic dehydration, recurrent infections, and diarrhea and intestinal malabsorption. The disease course is heterogeneous: the generalized erythroderma may persist in some patients, but more frequently it evolves during childhood into ichthyosis linearis circumflexa (ILC). ILC is a milder and highly characteristic skin disorder marked by migratory erythematous plaques with a double-edged scale.
Netherton syndrome Other names Comèl-Netherton syndrome Netherton syndrome has an autosomal recessive pattern of inheritance . Specialty Medical genetics Netherton syndrome is a severe, autosomal recessive [1] form of ichthyosis associated with mutations in the SPINK5 gene. [2] [3] It is named after Earl W. Netherton (1910–1985), an American dermatologist who discovered it in 1958. [4] Contents 1 Signs and symptoms 2 Cause 3 Diagnosis 4 Treatment 5 See also 6 References 7 External links Signs and symptoms [ edit ] Netherton syndrome is characterized by chronic skin inflammation, universal pruritus (itch), severe dehydration, and stunted growth. Patients with this disorder tend to have a hair shaft defect ( trichorrhexis invaginata ), also known as "bamboo hair". The disrupted skin barrier function in affected individuals also presents a high susceptibility to infection and allergy , leading to the development of scaly, reddish skin similar to atopic dermatitis . [5] In severe cases, these atopic manifestations persist throughout the individual's life, and consequently post-natal mortality rates are high.
Netherton syndrome is a disorder that affects the skin, hair, and immune system. Newborns with Netherton syndrome have skin that is red and scaly (ichthyosiform erythroderma), and the skin may leak fluid. Some affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life. Because newborns with this disorder are missing the protection provided by normal skin, they are at risk of becoming dehydrated and developing infections in the skin or throughout the body (sepsis), which can be life-threatening. Affected babies may also fail to grow and gain weight at the expected rate (failure to thrive).
SHH mutations were found in 67 (10.4%) probands. The patients had alobar (28%), semilobar (34%), lobar (4%), or microform (34%) HPE, but the 4 categories of facial defects were evenly distributed, although the proportion of coloboma was relatively high (15% for the series as a whole).
A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome. A form of holoprosencephaly (HPE10) has been mapped within the deleted region of chromosome 1q41-q42. For a general phenotypic description and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100). See also congenital diaphragmatic hernia (DIH; 142340), which has been associated with deletion of chromosome 1q41-q42. See also Skraban-Deardorff syndrome (SKDEAS; 617616), caused by mutation in the WDR26 gene (617424) on chromosome 1q42, which shows overlapping features with chromosome 1q41-q42 deletion syndrome.
A number sign (#) is used with this entry because of evidence that holoprosencephaly-4 (HPE4) is caused by heterozygous mutation in the TGIF gene (602630) on chromosome 18p11. For phenotypic information and a general discussion of genetic heterogeneity in holoprosencephaly, see HPE1 (236100). Cytogenetics Johnson and Bachman (1976) described a normal female who appeared to have a nonreciprocal translocation from the short arm of one chromosome 18 to the long arm of a chromosome 12. She gave birth to a cebocephalic child whose karyotype included an 18p- chromosome. The association of loss of 18p with holoprosencephaly was suggested by the patient reported by Munke et al. (1988); cytogenetic and molecular studies indicated a Y/18 translocation with loss of 18p and distal Yq material in a holoprosencephalic fetus.
A number sign (#) is used with this entry because holoprosencephaly-11 (HPE11) is caused by heterozygous mutation in the CDON gene (608707) on chromosome 11q24. For a general phenotypic description and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100). Clinical Features Bae et al. (2011) reported 4 unrelated patients with HPE11. One patient had agenesis of the corpus callosum, hypotelorism, growth hormone deficiency, global developmental delay, and thick eyebrows with synophrys. Another had agenesis of the corpus callosum, alobar HPE, hypotelorism, cleft lip/palate, and absent columella; absent pituitary and polysplenia were noted in this patient at autopsy.
This article needs additional citations for verification . Please help improve this article by adding citations to reliable sources . Unsourced material may be challenged and removed. Find sources: "Holoprosencephaly" – news · newspapers · books · scholar · JSTOR ( July 2009 ) ( Learn how and when to remove this template message ) Holoprosencephaly Diagram depicting the main subdivisions of the embryonic vertebrate brain. Specialty Medical genetics Holoprosencephaly ( HPE ) is a cephalic disorder in which the prosencephalon (the forebrain of the embryo ) fails to develop into two hemispheres . Normally, the forebrain is formed and the face begins to develop in the fifth and sixth weeks of human pregnancy . The condition also occurs in other species. The condition can be mild or severe.
For a phenotypic description and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100). Clinical Features Levin and Surana (1991) described holoprosencephaly in association with an interstitial deletion of chromosome 14q11.1-q13. Parental karyotypes were normal. The white female, born to nonconsanguineous young parents after an uncomplicated pregnancy, showed hypotelorism, lack of nasal bridge, flattened nasal tip with no visible septum, wide midline cleft of lip and hard palate, and ptosis of the left upper eyelid. Axial CT scan of the head was interpreted as showing semilobar holoprosencephaly. The infant died at 8 days of age. Kamnasaran et al. (2005) reported 6 patients with HPE and interstitial deletions on proximal chromosome 14q: 1 had alobar HPE and 5 had lobar HPE.
For phenotypic information and a general discussion of genetic heterogeneity in holoprosencephaly (HPE), see HPE1 (236100). Clinical Features Lehman et al. (2001) described a female infant who survived for 5.5 hours after delivery at 33 weeks' gestation. Autopsy showed a lobar variant of holoprosencephaly. Cytogenetics By cytogenetic analysis in an infant with a lobar variant of holoprosencephaly, Lehman et al. (2001) identified a 2q37.1-q37.3 deletion. This case represented the fourth reported case of HPE associated with partial monosomy 2q37 and the first with an apparently isolated 2q37 deletion. Lehman et al. (2001) suggested that the deleted segment may contain yet another locus, here designated HPE6, which, when disrupted, can lead to brain malformations within the HPE spectrum.
Nonsyndromic holoprosencephaly is an abnormality of brain development that also affects the head and face. Normally, the brain divides into two halves (hemispheres ) during early development. Holoprosencephaly occurs when the brain fails to divide properly into the right and left hemispheres. This condition is called nonsyndromic to distinguish it from other types of holoprosencephaly caused by genetic syndromes, chromosome abnormalities, or substances that cause birth defects (teratogens). The severity of nonsyndromic holoprosencephaly varies widely among affected individuals, even within the same family.
Holoprosencephaly is an abnormality of brain development in which the brain doesn't properly divide into the right and left hemispheres. The condition can also affect development of the head and face. There are 4 types of holoprosencephaly, distinguished by severity. From most to least severe, the 4 types are alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). In general, the severity of any facial defects corresponds to the severity of the brain defect. The most severely affected people have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye.
A number sign (#) is used with this entry because of evidence that holoprosencephaly-7 (HPE7) is caused by heterozygous mutation in the PTCH1 gene (601309) on chromosome 9q22. For phenotypic information and a general discussion of genetic heterogeneity in holoprosencephaly, see HPE1 (236100). Description Holoprosencephaly (HPE) is the most commonly occurring congenital structural forebrain anomaly in humans. HPE is associated with mental retardation and craniofacial malformations. Considerable heterogeneity in the genetic causes of HPE has been demonstrated (Ming et al., 2002).
A number sign (#) is used with this entry because of evidence that solitary median maxillary central incisor (SMMCI) and SMMCI syndrome are caused by heterozygous mutation in the Sonic hedgehog gene (SHH; 600725) on chromosome 7q36. Clinical Features Rappaport et al. (1976, 1977) reported 7 unrelated patients with single (unpaired) deciduous and permanent maxillary central incisors and short stature. Five of them had isolated growth hormone deficiency. The other 2 had normal growth hormone responses but were short of stature. No similar or possibly related abnormalities were present in the 7 families. Rappaport et al. (1976) used the term monosuperoincisivodontic dwarfism to describe the association of short stature and solitary incisor.
Description Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain and occurs after failed or abbreviated midline cleavage of the developing brain during the third and fourth weeks of gestation. HPE occurs in up to 1 in 250 gestations, but only 1 in 8,000 live births (Lacbawan et al., 2009). Classically, 3 degrees of severity defined by the extent of brain malformation have been described. In the most severe form, 'alobar HPE,' there is a single ventricle and no interhemispheric fissure. The olfactory bulbs and tracts and the corpus callosum are typically absent.
A rare complex brain malformation characterized by incomplete cleavage of the prosencephalon, and affecting both the forebrain and face and resulting in neurological manifestations and facial anomalies of variable severity. Epidemiology Prevalence is estimated to be 1/10,000 live and still births and 1/250 conceptuses, with worldwide distribution. Clinical description Three classical forms of holoprosencephaly (HPE) of increasing severity are described based on the degree of anatomical separation: lobar, semi-lobar and alobar HPE. Milder subtypes include midline interhemispheric variant and septopreoptic HPE. There is, however, a continuous spectrum of abnormal separation of the hemispheres that extends from aprosencephaly/atelencephaly, the most severe end of the spectrum, to microform HPE, a less severe midline defect without the typical HPE brain characteristics.
Callier et al. (2005) tabulated the clinical and cytogenetic findings in 28 reported cases of MVA syndrome. They also reported the first case of MVA syndrome without microcephaly and suggested that microcephaly is not mandatory for the diagnosis of the disorder.
A number sign (#) is used with this entry because mosaic variegated aneuploidy syndrome-2 (MVA2) is caused by homozygous or compound heterozygous mutation in the CEP57 gene (607951) on chromosome 11q21. Description Mosaic variegated aneuploidy syndrome is an autosomal recessive disorder characterized by poor growth and variable phenotypic manifestations, such as facial dysmorphism and congenital heart defects, associated with mosaic aneuploidies resulting from defects in cell division (summary by Snape et al., 2011). See also MVA1 (257300), caused by mutation in the BUB1B gene (602860) on chromosome 15q15. Clinical Features Lane et al. (2002) reported a 12-year-old boy with poor growth, short stature, microcephaly, mild cognitive defects, and mildly dysmorphic facial features. Cytogenetic analysis found 24% hyperdiploid chromosome numbers during metaphase, consistent with MVA.
Mosaic variegated aneuploidy (MVA) syndrome is a rare disorder in which some cells in the body have an abnormal number of chromosomes instead of the usual 46 chromosomes , a situation known as aneuploidy. Most commonly, cells have an extra chromosome, which is called trisomy, or are missing a chromosome, which is known as monosomy. In MVA syndrome, some cells are aneuploid and others have the normal number of chromosomes, which is a phenomenon known as mosaicism . Typically, at least one-quarter of cells in affected individuals have an abnormal number of chromosomes. Because the additional or missing chromosomes vary among the abnormal cells, the aneuploidy is described as variegated.
A number sign (#) is used with this entry because of evidence that mosaic variegated aneuploidy syndrome-3 (MVA3; 617598) is caused by homozygous mutation in the TRIP13 gene (604507) on chromosome 5p15. Description MVA3 is an autosomal recessive disorder resulting from errors in chromosome segregation. Most affected individuals develop early-onset Wilms tumor and show either aneuploidy or premature chromatid separation in cells. Some patients may have additional developmental features, such as microcephaly, growth retardation, or developmental delay (summary by Yost et al., 2017). For a discussion of genetic heterogeneity of MVA, see MVA1 (257300). Clinical Features Yost et al. (2017) reported 6 probands with onset of Wilms tumor in early childhood.
Mosaic variegated aneuploidy (MVA) syndrome is a very rare condition characterized by problems with cell division (specifically during mitosis) that results in a high number of cells with missing (monosomy) or extra (trisomy) genetic material in multiple chromosomes and tissues (mosaic aneuploidies). Only about 50 cases have been described in the medical literature. Features include severe microcephaly, growth deficiency and short stature, mild physical abnormalities, eye abnormalities, problems with the brain and central nervous system, seizures, developmental delay, and intellectual disability. The risk for cancer is increased, with rhabdomyosarcoma , Wilm's tumor , and leukemia reported in several cases. MVA syndrome is an autosomal recessive condition. It can be caused by changes (mutations) in the BUB1B gene or the CEP57 gene. The BUB1B gene encodes BubR1, a key protein in mitotic spindle checkpoint function.
Mosaic variegated aneuploidy (MVA) syndrome is a chromosomal anomaly characterized by multiple mosaic aneuploidies that leads to a variety of phenotypic abnormalities and cancer predisposition. Epidemiology To date, 41 cases of MVA have been described in the literature. Clinical description The most common clinical features are growth retardation of prenatal onset, microcephaly, developmental delay, structural central nervous system and ophthalmological anomalies (e.g. cataract, corneal opacities, microphthalmia and glaucoma), and mild dysmorphic features, including triangular facies, micrognathia, and epicanthic folds. Additional features include oligohydramnios, ventricular dilatation, Dandy-Walker malformation, fetal ascites, and increased nuchal translucency. Cancer occurs in approximately 1/3 of individuals. Wilms tumor, rhabdomyosarcoma, acute lymphoblastic leukemia, and granulosa cell malignant tumor of the ovary (see these terms) all occur before the age of 5 years.
The doubly heterozygous patients exhibited marked left ventricular hypertrophy, which was significantly greater than that in the other affected individuals. In a 28-year-old Australian man with CMH who had previously been studied by Ingles et al. (2005) and found to be compound heterozygous for missense mutations in the MYBPC3 gene (600958.0021 and 600958.0022), Chiu et al. (2007) also identified a heterozygous R73Q substitution in the CALR3 gene (611414).
