In Autosomal Dominant Inheritance Asp Pag
⚡ ALL INFORMATION CLICK HERE 👈🏻👈🏻👈🏻
In Autosomal Dominant Inheritance Asp Pag
Dashboard
Publications
Account settings
Log out
MedGen
National Center for Biotechnology Information
Format Full Report Summary (Text) Summary (XML)
MedGen UID: 141047 • Concept ID: C0443147 • Genetic Function; Intellectual Product
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. [from HPO ]
Sharma A,
Bosman LP,
Tichnell C,
Nanavati J,
Murray B,
Nonyane BAS,
Tandri H,
Calkins H,
James CA
Circ Genom Precis Med
2022 Jun;15(3):e003530.
Epub 2022 May 17
doi: 10.1161/CIRCGEN.121.003530.
PMID: 35579515
Cortés-Martín J,
Díaz-Rodríguez L,
Piqueras-Sola B,
Rodríguez-Blanque R,
Bermejo-Fernández A,
Sánchez-García JC
Int J Environ Res Public Health
2020 Aug 25;17(17)
doi: 10.3390/ijerph17176174.
PMID: 32854429 Free PMC Article
Waung MW,
Taylor A,
Qualmann KJ,
Burish MJ
JAMA Neurol
2020 Jul 1;77(7):887-896.
doi: 10.1001/jamaneurol.2020.0682.
PMID: 32310255 Free PMC Article
Gasser S,
Reichenspurner H,
Girdauskas E
BMC Cardiovasc Disord
2018 Feb 27;18(1):41.
doi: 10.1186/s12872-018-0755-y.
PMID: 29486707 Free PMC Article
Berciano J,
García A,
Gallardo E,
Peeters K,
Pelayo-Negro AL,
Álvarez-Paradelo S,
Gazulla J,
Martínez-Tames M,
Infante J,
Jordanova A
J Neurol
2017 Aug;264(8):1655-1677.
Epub 2017 Mar 31
doi: 10.1007/s00415-017-8474-3.
PMID: 28364294
PubMed Clinical Queries
Reviews in PubMed
Related information in PubMed Central Links
Related literature resources in PubMed
External link. Please review our privacy policy .
An official website of the United States government
The .gov means it's official.
Federal government websites often end in .gov or .mil. Before
sharing sensitive information, make sure you're on a federal
government site.
The site is secure.
The https:// ensures that you are connecting to the
official website and that any information you provide is encrypted
and transmitted securely.
Autosomal dominant; Autosomal Dominant
Autosomal dominant inheritance (263681008); Autosomal dominant (263681008); AD - Autosomal dominant (263681008)
Dashboard
Publications
Account settings
Log out
Search term All GTR Conditions/Phenotypes Genes Human Tests Microbe Tests Labs Search Advanced search for tests
GTR Home
>
Conditions/Phenotypes
>
Atypical hemolytic-uremic syndrome with C3 anomaly
Atypical hemolytic-uremic syndrome with C3 anomaly Synonyms AHUS, SUSCEPTIBILITY TO, 5 ; Atypical hemolytic-uremic syndrome 5
Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. The onset of atypical HUS (aHUS) ranges from the neonatal period to adulthood. Genetic aHUS accounts for an estimated 60% of all aHUS. Individuals with genetic aHUS frequently experience relapse even after complete recovery following the presenting episode; 60% of genetic aHUS progresses to end-stage renal disease (ESRD). Full text of GeneReview (by section): Summary Diagnosis Clinical Characteristics Genetically Related (Allelic) Disorders Differential Diagnosis Management Genetic Counseling Resources Molecular Genetics Chapter Notes References Authors: Marina Noris Elena Bresin Caterina Mele view full author information
Genes reported to contribute to the condition.
C Clinical
test , R
Research test , O
OMIM , G
GeneReviews
Clinical features Help List of clinical features of the condition/phenotype displayed from sources such as the Human Phenotype Ontology (HPO) and OMIM. For more information about the disease, please go to the disease information page.
Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom.
External link. Please review our privacy policy .
An official website of the United States government
The .gov means it's official.
Federal government websites often end in .gov or .mil. Before
sharing sensitive information, make sure you're on a federal
government site.
The site is secure.
The https:// ensures that you are connecting to the
official website and that any information you provide is encrypted
and transmitted securely.
Check Related conditions for additional relevant tests.
Also known as: AHUS5, ARMD9, ASP, C3a, C3b, CPAMD1, HEL-S-62p, C3 Summary: complement C3
Abnormality of blood and blood-forming tissues
Abnormality of blood and blood-forming tissues
Abnormality of blood and blood-forming tissues
Abnormality of metabolism/homeostasis
Abnormality of metabolism/homeostasis
Abnormality of the cardiovascular system
Abnormality of the genitourinary system
Abnormality of the genitourinary system
Abnormality of the genitourinary system
Abnormality of the genitourinary system
Abnormality of the genitourinary system
IMPORTANT NOTE: NIH does not independently verify information submitted to the GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in the GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Dashboard
Publications
Account settings
Log out
Adam MP, Everman DB, Mirzaa GM, et al., editors.
Perinatal (severe): characterized by pulmonary insufficiency and hypercalcemia
Perinatal (benign): prenatal skeletal manifestations that slowly resolve into one of the milder forms
Infantile: onset between birth and age six months of clinical features of rickets without elevated serum alkaline phosphatase activity
Severe childhood (juvenile): variable presenting features progressing to rickets
Mild childhood: low bone mineral density for age, increased risk of fracture, and premature loss of primary teeth with intact roots
Adult: characterized by stress fractures and pseudofractures of the lower extremities in middle age, sometimes associated with early loss of adult dentition
Odontohypophosphatasia: characterized by premature exfoliation of primary teeth and/or severe dental caries without skeletal manifestations
Perinatal (severe) type: growing experience with asfotase alfa enzyme replacement therapy (ERT); expectant management and family support; respiratory support; management of calcium homeostasis and bone health per endocrinologist and orthopedist; pain management; neurosurgical management of craniosynostosis; management of renal disease per nephrologist; dental care.
Infantile and early childhood (juvenile) types: ERT; respiratory support; management of calcium homeostasis and bone health per endocrinologist and orthopedist; pain management; treatment of seizures with vitamin B 6 ; neurosurgical management of craniosynostosis; management of renal disease per nephrologist; dental care.
All other types: dental care starting at age one year; nonsteroidal anti-inflammatory drugs for osteoarthritis, bone pain, and osteomalacia; internal fixation for pseudofractures and stress fractures. In adult hypophosphatasia, there is limited experience in treating osteomalacia with teriparatide and emerging experience with ERT.
Autosomal recessive hypophosphatasia. If both parents are known to be heterozygous for an ALPL pathogenic variant , each sib of an affected individual has at conception a 25% chance of inheriting biallelic pathogenic variants and being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither of the familial pathogenic variants. Depending on the ALPL pathogenic variant, heterozygous sibs may be either clinically asymptomatic (manifesting only biochemical abnormality) or have milder clinical symptoms than the proband .
Autosomal dominant hypophosphatasia. All individuals reported to date with hypophosphatasia caused by a heterozygous ALPL variant with a dominant-negative effect have inherited the ALPL pathogenic variant from a parent (who may or may not have clinical manifestations of hypophosphatasia). Unless an individual with autosomal dominant hypophosphatasia has children with an individual who has a heterozygous or biallelic ALPL pathogenic variant(s), his/her offspring have a 50% chance of inheriting the ALPL pathogenic variant.
Clinical features of infantile rickets: growth failure, craniotabes, craniosynostosis, blue sclerae, flail chest, costochondral enlargement ("rachitic rosary"), scoliosis, thickening of wrists, knees, and ankles, bowing of legs, lax ligaments, and hypotonia
Premature loss of deciduous teeth beginning with the incisors. Unusually and characteristically, the dental root remains attached to the lost tooth. Dental caries and early loss or extraction of adult teeth is also seen ( Figure 1 ).
Vitamin B 6 (pyridoxine)-responsive seizures
Hypercalciuria particularly during the first year of life with or without hypercalcemia
Typically normal serum calcium and ionized calcium. Note: May be elevated, particularly in the first year of life.
Typically normal serum and urine inorganic phosphate. Note: May be elevated.
Normal serum vitamin D (25-hydroxy and 1,25-dihydroxy) and parathyroid hormone
Elevated plasma vitamin B 6 without oral supplementation
Elevated serum pyridoxal 5'-phosphate (PLP) , a biologically active metabolite of vitamin B 6 . Note: (1) Reference laboratories may measure PLP and report as "vitamin B 6 ." (2) Use of multivitamin or calcium supplements containing vitamin B 6 within a week of assaying serum PLP may lead to false positive results.
Elevated urine phosphoethanolamine (PEA) and proline on urine amino acid chromatogram. Note: (1) Urine PEA may be elevated with other metabolic bone diseases. (2) Urine PEA may be normal in affected individuals and can be elevated in asymptomatic heterozygotes.
Elevated urine inorganic pyrophosphate (PPi). Note: (1) Assay is not available in North American clinical laboratories. (2) Asymptomatic heterozygotes can have elevated urine PPi.
Reduced serum unfractionated alkaline phosphatase (ALP) activity. Note: (1) Transient increases in serum ALP activity can occur during pregnancy, with liver disease, and after acute fracture or surgery. Thus, serial measurements may be necessary in toddlers with unexplained fractures. Quantitation of the activity of the bone isoform of ALP in serum may be necessary in the setting of liver disease. The bone isoform is heat labile; the liver isoform is heat stable. (2) Asymptomatic heterozygotes can have reduced serum ALP activity.
Prenatal long bone bowing with osteochondral spurs
Infantile rickets: undermineralized bones, widened-appearing sutures, brachycephaly, rachitic costochondral rib changes ( Figure 2A ), flared metaphyses, poorly ossified epiphyses, and bowed long bones
Focal bony defects of the metaphyses resembling radiolucent "tongues" ( Figure 2C ) are fairly specific for childhood hypophosphatasia.
Defective mineralization of growing/remodeling bone and/or teeth. Bone mineral content increases with age, and there may be improved mineralization during adolescence with decreased mineralization in middle age.
Alveolar bone loss resulting in premature loss of deciduous teeth typically involving the anterior mandible, with the central incisors lost first. However, any tooth may be affected ( Figure 2B ).
Pathologic fractures. Growing children may have a predilection to metaphyseal fractures; however, epiphyseal and diaphyseal fractures are also seen. In adults, metatarsal stress fractures and femoral pseudofractures prevail.
Osteomalacia with lateral pseudofractures ("Looser zones") in adult hypophosphatasia ( Figure 2D )
Biallelic loss-of-function ALPL variants
A heterozygous ALPL variant with dominant-negative effect
Additional clinical & radiographic features of infantile rickets 1, 2
Alveolar bone loss (anterior mandible)
Focal metaphyseal defects resembling radiolucent "tongues"
Stress fractures: metatarsal, tibia
Dental caries & early loss or extraction of adult teeth
Bone histology reveals rachitic abnormalities of the growth plate. Histochemical testing of osteoclasts reveals lack of membrane-associated ALP activity. Osteoclasts and osteoblasts otherwise appear normal.
Tooth histology reveals a decrease in cementum, which varies with the severity of the disease.
↑ serum alkaline phosphatase activity
Serum calcium, phosphorus, magnesium
Referral to endocrinologist for mgmt of bone health
Skeletal survey incl radiographs of skull to assess for craniosynostosis
Blood urea nitrogen & serum creatinine concentration
Social work involvement for parental support;
Skeletal survey incl radiographs of skull to assess for craniosynostosis
Serum 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, & nPTH to assess for confounding comorbidity (e.g., vitamin D deficiency)
Referral to endocrinologist for mgmt of bone health
Blood urea nitrogen & serum creatinine concentration
Respiratory support per pulmonologist
Asfotase alfa ERT has been shown to improve survival & pulmonary function.
Physical medicine & rehab, PT, & OT to optimize mobility & autonomy
Low-impact physical activity & exercise
Mgmt of primary & secondary skeletal manifestations per orthopedist
Internal fixation has been suggested as optimal mgmt.
Consider foot orthotics for tarsal fractures & pseudofractures in adults.
Teriparatide ↑s production of TNSALP in osteoblasts. To date, there are no prospective studies or clinical trials. Improvement in biochemical markers & bone mineral density have been mixed. 3
Teriparatide is contraindicated in children (see Agents/Circumstances to Avoid ).
Mgmt per neurologist to prophylactically or prospectively treat seizures & manage myopathy
Seizures may respond to treatment w/vitamin B 6 (pyridoxine).
The parents of a child with biallelic ALPL pathogenic variants are typically heterozygous for one ALPL pathogenic variant .
Molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for an ALPL pathogenic variant and to allow reliable recurrence risk assessment.
If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, it is possible that one of the pathogenic variants identified in the proband occurred as a de novo event in the proband [ Taillandier et al 2005 , Zhang et al 2012 ] or as a postzygotic de novo event in a mosaic parent. If the proband appears to have homozygous pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:
A single- or multiexon deletion in the proband that was not detected by sequence analysis and that resulted in the artifactual appearance of homozygosity;
Uniparental isodisomy for the parental chromosome with the pathogenic variant that resulted in homozygosity for the pathogenic variant in the proband [ Watanabe et al 2014 , Hancarova et al 2015 ].
Depending on the ALPL pathogenic variant , heterozygous parents are either clinically asymptomatic (manifesting only biochemical abnormality) or have milder clinical symptoms than their child (see Molecular Pathogenesis ).
If both parents are known to be heterozygous for an ALPL pathogenic variant , each sib of an affected individual has at conception a 25% chance of inheriting biallelic pathogenic variants, a 50% chance of being heterozygous, and a 25% chance of inheriting neither of the familial pathogenic variants.
Sibs who inherit biallelic pathogenic variants tend to have similar disease severity; however, growth differences, nutrition, activity level, and earlier age of diagnosis all may influence phenotype . Sibs with compound heterozygous variants tend to display less intrafamilial clinical variability at the severe end of the spectrum and more variability at the milder end of the spectrum.
Depending on the ALPL pathogenic variant , heterozygous sibs may be either clinically asymptomatic (manifesting only biochemical abnormality) or have milder clinical symptoms than the proband (see Molecular Pathogenesis ).
All individuals reported to date with hypophosphatasia caused by a heterozygous ALPL variant with a dominant-negative effect have inherited the ALPL pathogenic variant from a parent (who may or may not have clinical manifestations of hypophosphatasia).
Recommendations for the evaluation of parents of a proband include review of clinical history and laboratory evaluations for signs of hypophosphatasia. Molecular genetic testing is recommended for the parents of the proband to confirm their genetic status and to allow reliable recurrence risk counseling.
If the pathogenic variant identified in the proband is not identified in either parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:
The proband inherited a pathogenic variant from a parent with germline (or somatic and germline) mosaicism . Note: Testing of parental leukocyte DNA may not detect all instances of somatic mosaicism and will not detect a pathogenic variant that is present in the germ cells only.
Evaluation of parents may determine that a parent is affected but has escaped previous diagnosis because of failure by health care professionals to recognize the disorder, reduced penetrance , and/or a milder phenotypic presentation. Therefore, an apparently negative family history cannot be confirmed unless molecular genetic testing has demonstrated that neither parent is heterozygous for the ALPL pathogenic variant identified in the proband .
If a parent of the proband is known to have the pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%.
Clinical severity is often similar in affected family members but cannot be reliably predicted by family history or molecular genetic testing due to reduced penetrance and variable expressivity .
If the ALPL pathogenic variant identified in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is estimated to be 1% because of the theoretic possibility of parental germline mosaicism [ Rahbari et al 2016 ].
The optimal time for determination of genetic risk and discussion of the availability of prenatal/ preimplantation genetic testing is before pregnancy.
It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are heterozygous , or are at risk of being heterozygous.
Molecular genetic testing. Once the ALPL pathogenic variant (s) have been identified in an affected family member, prenatal testing and preimplantation genetic testing
Hoodamateurs.Com
Kate Hudson Upskirt
Ernies House Of Whoopass