• For a long time, autosomal recessive inheritance has been considered a unique feature of type 3 von Willebrand disease (VWD), which is characterized by the virtual absence of von Willebrand factor (VWF) in plasma and storage compartments. (karger.com)
  • In recent years, it has been demonstrated that this type of inheritance is also present in some type 1 and 2 families, previously considered the epitome of true dominant transmission. (karger.com)
  • We report our experience with 12 families with clearly recessive inheritance, but definitely measurable factor VIII and VWF, which is not typical for severe type 3 VWD. (karger.com)
  • Eikenboom JCJ, Reitsma PH, Peerlinck KMJ, Briët E: Recessive inheritance of von Willebrand's disease type I. Lancet 1993;341:982-986. (karger.com)
  • elevated levels of IgE and that follow an autosomal recessive pattern of inheritance. (nih.gov)
  • NMNAT1 RD3 RDH12 RPGRIP1 SPATA7 TULP1 USP45 Leber congenital amaurosis usually has an autosomal recessive pattern of inheritance. (nih.gov)
  • The mutation followed a Mendalian pattern with an autosomal recessive inheritance mode. (illumina.com)
  • The dystrophies typically have an autosomal dominant inheritance and involve Bowman layer and stroma (3). (uiowa.edu)
  • This type of inheritance is called autosomal recessive inheritance. (nih.gov)
  • You may inherit this from one parent and be affected (autosomal dominant inheritance, 50% chance of transmission to children) or from both parents (autosomal recessive inheritance, 25% chance of transmission to children if both parents carry the gene mutation and do not have symptoms). (bcm.edu)
  • MPSI follows an autosomal recessive mode of inheritance. (wisdompanel.com)
  • Patients with head circumference at least three standard deviations below the age and sex mean, with or without central nervous system anomalies, and with a family history consistent with autosomal recessive mode of inheritance (Bacino et al. (preventiongenetics.com)
  • Inheritance is autosomal recessive or autosomal dominant. (msdmanuals.com)
  • and an autosomal recessive or autosomal dominant form of inheritance. (medscape.com)
  • Type I features autosomal dominant inheritance and distal sensory involvement. (bvsalud.org)
  • Type II is characterized by autosomal inheritance and distal and proximal sensory loss. (bvsalud.org)
  • Mutations in subunit of the mitochondrial DNA polymerase (POLG) have been found to be a potential cause of autosomal recessive cerebellar ataxia. (wikipedia.org)
  • In conclusion, patients with recessive FBLN4 mutations are predominantly characterized by aortic aneurysms, arterial tortuosity and stenosis. (uzh.ch)
  • In this study, by targeted next-generation sequencing of 414 known deafness genes, we identified compound heterozygous mutations p.R34X/p.M413T in TMC1 and p.S3417del/p.R1407T in MYO15A in two recessive Chinese Han deaf families. (hindawi.com)
  • Auditory features of the affected individuals are consistent with that previously reported for recessive mutations in TMC1 and MYO15A . (hindawi.com)
  • It has been reported that mutations in TMC1 may cause both prelingual profound autosomal recessive deafness DFNB7/11 and postlingual progressive autosomal dominant deafness DFNA36 [ 13 ]. (hindawi.com)
  • To date, more than 60 mutations in TMC1 are reported worldwide [ 15 ], with the recessive mutations predominantly associated with prelingual severe-to-profound hearing loss [ 15 , 16 ]. (hindawi.com)
  • Pathogenic mutations in the gene encoding the giant skeletal muscle protein titin (TTN) are associated with several muscle disorders, including cardiomyopathy, recessive congenital myopathies and limb-girdle muscular dystrophy (LGMD) type10. (biomedcentral.com)
  • To have an autosomal recessive disorder, you inherit two changed genes, sometimes called mutations. (mayoclinic.org)
  • The four main types of sickle cell anemia are caused by different mutations in these genes. (healthline.com)
  • Mutations in this gene cause Charcot-Marie-Tooth disease type 2A2, and hereditary motor and sensory neuropathy VI, which are both disorders of the peripheral nervous system. (nih.gov)
  • Mutations in any of three genes, ETFA , ETFB , and ETFDH , can result in glutaric acidemia type II. (medlineplus.gov)
  • People with mutations that result in a complete loss of either enzyme produced from the ETFA , ETFB or ETFDH genes are likely to experience the most severe symptoms of glutaric acidemia type II. (medlineplus.gov)
  • Glutaric acidemia type II: gene structure and mutations of the electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) gene. (medlineplus.gov)
  • X-linked hypophosphatemic rickets and autosomal recessive hypophosphatemic rickets are the result of mutations in PHEX (a phosphate-regulating gene with homologies to endopeptidases on the X chromosome) and dentin matrix protein 1 ( DMP1 ), respectively. (medscape.com)
  • A type of autosomal recessive pure hereditary spastic paraplegia characterized by infancy onset of crural spastic paraperesis with scissors gait, extensor plantar response, and increased tendon reflexes. (orpha.net)
  • Autosomal recessive spastic ataxia of Charlevoix-Saguenay, more commonly known as ARSACS, is a condition affecting muscle movement. (nih.gov)
  • Autosomal recessive spastic paraplegia type 57 (SPG57) is an extremely rare complex type of hereditary spastic paraplegia characterized by onset in infancy of pronounced leg spasticity (leading to the inability to walk independently) reduced visual acuity due to optic atrophy and distal wasting of the hands and feet due to an axonal demyelinating sensorimotor neuropathy. (globalgenes.org)
  • Newly diagnosed with Autosomal recessive spastic paraplegia type 57? (globalgenes.org)
  • Abstract Objective: To identify the gene mutation responsible for a family presenting spastic paraplegia, cerebellar ataxia and neuropathy with autosomal recessive transmission. (symptoma.com)
  • Hereditary spastic paraplegia type 18 (HSP18) is a complicated form of autosomal recessive HSP characterized by progressive weakness and spasticity of the lower extremities, dysarthria , and cognitive decline. (symptoma.com)
  • 1 Forty recessive deafness loci (DFNB) have been mapped and the genes responsible at 20 of these loci have been reported. (bmj.com)
  • The deafness segregating in family PKSN32 was not linked to any of the known recessive or dominant deafness loci (Hereditary Hearing Loss Homepage, http://dnalab-www.uia.ac.be/dnalab/hhh/ ). (bmj.com)
  • A maximum two-point LOD score of 4.1 (θ = 0) was obtained with marker D1S214 , defining a new recessive deafness locus, DFNB36 . (bmj.com)
  • The genes that underlie majority of the symptoms for the different types of ataxia are still unknown. (wikipedia.org)
  • Electrophysiologic studies for polyneuropathy Neurological examination Prenatal diagnosis and preimplantation genetic diagnosis (PGD) can be performed to identify the mothers carrying the recessive genes for cerebellar ataxia. (wikipedia.org)
  • 2019). Identification of novel genes associated with sequence type seems to be particularly virulent to anti-phagocytic functions in Streptococcus equi subsp. (cdc.gov)
  • These syndromes are now classified on the basis of at least 15 identified genes-5 autosomal dominant and 10 autosomal recessive. (medscape.com)
  • The 10 recessive genes are associated with the plasma basement membrane and the adjacent reticular lamina, which contains the fibrillary collagen. (medscape.com)
  • These genes are passed on in families using Mendelian principles (e.g., autosomal recessive or dominant). (cdc.gov)
  • This study describes its clinical spectrum, management outcomes and genetic associations in patients with autosomal recessive RP (arRP). (lu.se)
  • Fogel, Clinical Features and Molecular Genetics of ARCA Hakonen, Mitochondrial DNA Mutation "Autosomal recessive cerebellar Ataxia. (wikipedia.org)
  • Castaman G, Novella E, Castiglia E, Eikenboom JCJ, Rodeghiero F: A novel family with recessive von Willebrand disease due to compound heterozygosity for a splice site mutation and a missense mutation in the von Willebrand factor gene. (karger.com)
  • Castaman G, Bertoncello K, Bernardi M, Eikenboom JC, Budde U, Rodeghiero F: Autosomal recessive von Willebrand disease associated with compound heterozygosity for a novel nonsense mutation (2908 del C) and the missense mutation C2362F: definite evidence for the non-penetrance of the C2362F mutation. (karger.com)
  • Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. (nature.com)
  • To our knowledge this is the first case of an initiation codon mutation in a human crystallin gene, and only the second report of a CRYBB1 mutation associated with autosomal recessive congenital cataracts. (molvis.org)
  • In order to further delineate the molecular pathology of autosomal recessive cataracts, we investigated a consanguineous family with nuclear pulverulent cataracts and identified a novel germline CRYBB1 mutation. (molvis.org)
  • In this study, we documented a clinical and molecular investigation of a consanguineous Pakistani family segregating LGMD in an autosomal recessive form and identified a novel homozygous missense mutation in the TTN gene located on chromosome 2q31.2. (biomedcentral.com)
  • This disease is autosomal recessive meaning that two copies of the mutation are needed for disease signs to be shown. (wisdompanel.com)
  • A recessive mutation of ESPN is known to cause hearing loss and vestibular dysfunction in the jerker mouse. (bmj.com)
  • The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. (medlineplus.gov)
  • The gene for the autosomal recessive form was identified as the ROR2 gene on chromosome 9q22. (nih.gov)
  • Autosomal dominant PKD is caused by a gene defect that is inherited from one parent. (childrens.com)
  • Autosomal recessive PKD is caused by a gene defect that must be inherited from both parents. (childrens.com)
  • In addition, although a number of genetic causes of autosomal dominant pulverulent cataracts have been identified (including CRYBB1 ) this is the first gene to have been implicated in autosomal recessive nuclear pulverulent cataract. (molvis.org)
  • R346P) in PAPSS2 Gene Results in Autosomal Recessive form of Brachyolmia Type 1 (Hobaek Form) in A Consanguineous Family. (illumina.com)
  • In an autosomal dominant disorder, the changed gene is a dominant gene. (mayoclinic.org)
  • You need only one changed gene to be affected by this type of disorder. (mayoclinic.org)
  • A person with an autosomal dominant disorder - in this example, the father - has a 50% chance of having an affected child with one changed gene. (mayoclinic.org)
  • Autosomal recessive polycystic kidney disease (ARPKD) is the most common heritable cystic renal disease occurring in infancy and childhood. (medscape.com)
  • [ 1 ] It is distinct from autosomal dominant polycystic kidney disease (ADPKD), which tends to occur in an older population. (medscape.com)
  • Ultrasonography is the primary radiologic modality for the evaluation of autosomal recessive polycystic kidney disease (ARPKD), especially during the perinatal and neonatal periods. (medscape.com)
  • What are the different types of Pediatric Polycystic Kidney Disease (PKD)? (childrens.com)
  • Autosomal dominant polycystic kidney disease (ADPKD). (mayoclinic.org)
  • In the past, this type was called adult polycystic kidney disease, but children can develop the disorder. (mayoclinic.org)
  • Most cases of autosomal recessive cerebellar ataxia are early onset, usually around the age of 20. (wikipedia.org)
  • citation needed] Clinical diagnosis is conducted on individuals with age onset between late teens and late forties who show the initial characteristics for the recessive autosomal cerebellar ataxia. (wikipedia.org)
  • The most typical presentation is limb-girdle muscular dystrophy type 2L (LGMD2L) with late-onset proximal lower-limb weakness in the fourth or fifth decade (range 15-70 years). (nih.gov)
  • Type B (juvenile onset) does not generally affect the brain but most children develop ataxia, damage to nerves exiting from the spinal cord (peripheral neuropathy), and pulmonary difficulties that progress with age. (nih.gov)
  • WWOX has been recently implicated in autosomal recessive spinocerebellar ataxia type 12 (SCAR12) and severe early-onset epileptic encephalopathy (EOEE). (bvsalud.org)
  • Glutaric acidemia type II is caused by a deficiency in either of these two enzymes. (medlineplus.gov)
  • Niemann-Pick types A and B result from accumulation of the fatty substance called sphingomyelin, due to deficiency of an enzyme called sphingomyelinase. (nih.gov)
  • Niemann-Pick disease type C is not caused by a deficiency of sphlingomyelinase but by a lack of the NPC1 or NPC2 proteins. (nih.gov)
  • Type IV features insensitivity to pain, heat intolerance, and mental deficiency. (bvsalud.org)
  • Eikenboom JCJ, Castaman G, Vos HL, Bertina RM, Rodeghiero F: Characterization of the genetic defects in recessive type 1 and type 3 von Willebrand disease patients of Italian origin. (karger.com)
  • Now that genetic testing is available, it can be performed to confirm the diagnosis of autosomal dominant OPCAs. (medscape.com)
  • This type is a much more rare and severe form that is caused by a genetic defect inherited from both parents. (childrens.com)
  • Alport syndrome can be transmitted as an X-linked, autosomal recessive , or autosomal dominant disorder. (nih.gov)
  • Autosomal recessive axonal neuropathy with neuromyotonia is a disorder that affects the peripheral nerves. (nih.gov)
  • Autosomal recessive is one of several ways that a trait, disorder, or disease can be passed down through families. (nih.gov)
  • Glutaric acidemia type II is an inherited disorder that interferes with the body's ability to break down proteins and fats to produce energy. (medlineplus.gov)
  • In the mildest forms of glutaric acidemia type II, muscle weakness developing in adulthood may be the first sign of the disorder. (medlineplus.gov)
  • Mucopolysaccharidosis Type I is a disorder causing failure to thrive, facial and other skeletal abnormalities, tremors, and clouding of the eyes. (wisdompanel.com)
  • Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that results from hypoplasia of the cerebral cortex. (preventiongenetics.com)
  • MPYCD is an autosomal recessive disorder caused by defects in the mitochondrial pyruvate carrier complex (Bricker et al. (preventiongenetics.com)
  • Autoimmune polyendocrine syndrome type II, also known as Schmidt syndrome, is a rare autoimmune disorder in which there is a steep drop in production of several essential hormones by the glands that secrete these hormones. (rarediseases.org)
  • Most congenital non-syndromic hearing loss is inherited as a recessive Mendelian disorder. (bmj.com)
  • In 2022, type 3 VDPV (VDPV3) was detected in stool specimens from an infant with primary immunodeficiency disorder (PID) through a pilot surveillance program to identify VDPVs in children with PIDs. (cdc.gov)
  • Autosomal recessive cerebellar ataxia type 1 (ARCA1) is a condition characterized by progressive problems with movement. (wikipedia.org)
  • http://ghr.nlm.nih.gov/condition/autosomal-recessive-cerebellar-ataxia-type-1 "Autosomal Recessive Cerebellar Ataxias. (wikipedia.org)
  • Orphanet Journal of Rare Diseases "Autosomal Recessive Cerebellar Ataxias. (wikipedia.org)
  • The classification of autosomal recessive ataxias takes into consideration the phenotypes There are different types of ataxias: congenital ataxias (developmental disorders) ataxias with metabolic disorders ataxias with a DNA repair defect degenerative ataxias ataxia associated with other features. (wikipedia.org)
  • Limb-girdle muscular dystrophies (LGMDs) are clinically and genetically heterogeneous muscle disorders inherited as an autosomal recessive or dominant pattern. (biomedcentral.com)
  • The prevalence of autosomal recessive muscle disorders like LGMD and congenital muscular dystrophies are rare in Pakistani populations. (biomedcentral.com)
  • Niemann-Pick disease is a group of autosomal recessive disorders caused by an accumulation of fat and cholesterol in cells of the liver, spleen, bone marrow, lungs, and, in some instances, brain. (nih.gov)
  • For autosomal recessive disorders, cats with two copies of the variant are at risk of developing the condition. (wisdompanel.com)
  • there are many types and subtypes, and other disorders may have overlapping phenotypes. (arupconsult.com)
  • Pseudohypoaldosteronism type I is a group of rare hereditary disorders that cause the kidneys to retain too much potassium but excrete too much sodium and water, leading to hypotension. (msdmanuals.com)
  • Studies have indicated abnormal synthesis of type II collagen in SED congenita. (medscape.com)
  • Although congenital, profound hearing loss with vestibular areflexia is accompanied by retinitis pigmentosa (RP) in Usher syndrome type 1, 3 affected individuals from PKSN32 or PKSR5A denied nyctalopia or other symptoms of RP. (bmj.com)
  • Connect with other caregivers and patients with Cutis laxa, autosomal recessive type 1 and get the support you need. (rareguru.com)
  • The Skeletal Dysplasia Management Consortium has developed best practice guidelines for diagnosis and management of type II collagen skeletal dysplasias (including SED). (medscape.com)
  • Glutaric acidemia type II usually appears in infancy or early childhood as a sudden episode called a metabolic crisis, in which acidosis and low blood glucose (hypoglycemia) cause weakness, behavior changes such as poor feeding and decreased activity, and vomiting. (medlineplus.gov)
  • Type A, the most severe form, begins in early infancy. (nih.gov)
  • To identify the molecular basis for autosomal recessively inherited congenital non-syndromic pulverulent cataracts in a consanguineous family with four affected children. (molvis.org)
  • People with this type of ataxia share many characteristic symptoms including:[citation needed] frequent falls due to poor balance imprecise hand coordination postural or kinetic tremor of extremities or trunk dysarthria dysphasia vertigo diplopia lower extremity tendon reflexes dysmetria minor abnormalities in ocular saccades attention defects impaired verbal working memory and visuospatial skills Normal life expectancy Autosomal recessive ataxias are generally associated with a loss of proprioception and vibration sense. (wikipedia.org)
  • Symptoms of autosomal dominant PKD often do not develop until a person is an adult, but can begin in childhood. (childrens.com)
  • Symptoms of autosomal recessive PKD are usually detected before birth during an ultrasound. (childrens.com)
  • While there are multiple types of SCD, they all have similar symptoms, which vary in severity. (healthline.com)
  • These types of sickle cell disease are more rare and usually don't have severe symptoms. (healthline.com)
  • It is typically an autosomal dominant, bilateral disease that typically presents toward the end of the first decade of life with symptoms of recurrent corneal erosions and decreased vision. (uiowa.edu)
  • When one of the enzymes is defective or missing, partially broken down nutrients accumulate in the cells and damage them, causing the signs and symptoms of glutaric acidemia type II. (medlineplus.gov)
  • It is characterized by slowly progressive yet milder neurologic symptoms compared to type 2 Gaucher disease. (nih.gov)
  • Rodeghiero F, Castaman G: von Willebrand disease type 1: definition, phenotypes, clinical and laboratory assessment. (karger.com)
  • Eikenboom JC: von Willebrand disease type 3: clinical manifestations, pathophysiology and molecular biology. (karger.com)
  • Tjernberg P, Castaman G, Vos HL, Bertina RM, Eikenboom JCJ: Homozygous C2362F von Willebrand factor induces intracellular retention of mutant von Willebrand factor resulting in autosomal recessive severe von Willebrand disease. (karger.com)
  • This type is inherited from at least one parent and is the most common form of the disease. (childrens.com)
  • What are the types of sickle cell disease? (healthline.com)
  • Hemoglobin SS disease is the most common type of sickle cell disease. (healthline.com)
  • Hemoglobin SC disease is the second most common type of sickle cell disease. (healthline.com)
  • Sickle beta-zero thalassemia is the fourth type of sickle cell disease. (healthline.com)
  • Type 1 (nonneuronopathic type) is the most common form of the disease in the U.S. and Europe. (nih.gov)
  • Type 2 (acute infantile neuropathic Gaucher disease) typically begins within three months of birth. (nih.gov)
  • Mucopolysaccharidosis Type 1 (MPSI) is a lysosomal storage disease caused by deficient activity of the alpha-L-iduronidase enzyme, which is used to break down dermatan and heparan sulfates. (wisdompanel.com)
  • GRS for various diseases, such as type 2 diabetes, hypertension, coronary heart disease, breast cancer, prostate cancer, multiple sclerosis, and others, have been developed but have largely undefined clinical validity and utility in unselected populations. (cdc.gov)
  • Here, discover the type of medical professionals that can help, tools for finding them, and tips for getting the most out of your care as you navigate to a diagnosis. (nih.gov)
  • The differential diagnosis should include other forms of CL (autosomal recessive type 2, autosomal dominant and X-lined CL) and related syndromes (gerodermia osteodysplastica, Cantu syndrome, wrinkly skin syndrome and De Barsy syndrome), together with the Ehlers-Danlos syndromes and Costello syndrome (see these terms). (rareguru.com)
  • therefore, family members must be evaluated early if a diagnosis of autosomal dominant OPCA is made. (medscape.com)
  • The diagnosis is based on the presence of spontaneous or medicated ST elevation, characterized by boost of the J point and the ST segment ≥ 2 mm, of superior convexity "hollow type" (subtype 1A) or descending rectilinear model (subtype 1B). (bvsalud.org)
  • skin.DOCK8 immunodeficiency syndrome is also commonly called autosomal recessive hyper-IgE syndrome. (nih.gov)
  • There are 3 types of Usher syndrome, and each type causes a different mix of hearing loss, balance issues , and vision problems. (nih.gov)
  • Camptodactyly syndrome, Guadalajara type 1 is a rare syndrome consisting of growth retardation, facial dysmorphism, camptodactyly and skeletal anomalies. (orpha.net)
  • Because an abnormality in type II collagen should affect the molecules throughout the body, it remains unclear how the currently defined abnormality can translate into major structural abnormalities of the vertebrae and capital femoral epiphysis while leaving the distal femur, proximal tibia, and other regions structurally unaffected. (medscape.com)
  • In the most severe cases of glutaric acidemia type II, affected individuals may also be born with physical abnormalities. (medlineplus.gov)
  • The autosomal recessive form tends to be severe and permanent. (msdmanuals.com)
  • The autosomal dominant form is usually less severe, affecting mainly the mineralocorticoid receptor in the kidney, and may resolve somewhat as children age. (msdmanuals.com)
  • WWOX and severe autosomal recessive epileptic encephalopathy: first case in the prenatal period. (bvsalud.org)
  • In many patients of these families with recessive VWD, molecular basis studies have provided insights into the molecular mechanisms responsible for the heterogeneity of phenotypes. (karger.com)
  • This study aimed to identify the pathogenic variant in a consanguineous Pakistani family with autosomal recessive LGMD type 10. (biomedcentral.com)
  • The variant p.Arg32936His leads to a substitution of the arginine amino acid at position 32,936 into histidine possibly causing LGMD type 10. (biomedcentral.com)
  • We identified a homozygous missense variant in TTN , which likely explains LGMD type 10 in this family in line with similar previously reported data. (biomedcentral.com)
  • [ 8 ] Kohn recognized an autosomal recessive variant of SED tarda associated with mental retardation. (medscape.com)
  • Type 3 (chronic neuronopathic form) can begin at any time in childhood or even in adulthood. (nih.gov)
  • SED Maroteaux type is a form with manifestations limited to the musculoskeletal system. (medscape.com)
  • [ 7 ] SED tarda Toledo type is a form of SED tarda with peripheral corneal opacities and a qualitative abnormality of urinary mucopolysaccharides, mainly chondroitin-6-sulfate. (medscape.com)
  • Not all patients wish to learn of their risks in the absence of an available treatment, while some individuals may use the information for family planning and other types of planning for the future. (medscape.com)
  • Of the 49 babies with multiple malformations, 21 (42.8%) had recog- nized syndromes, most of which were autosomal recessive and 17 had chromosomal aberrations. (who.int)
  • Salamon, T. Über eine Familie mit recessiver Kraushaarigkeit, Hypotrichose und anderen Anomalien [On a family with the recessive trait of woolly hair, hypotrichosis and other anomalies]. (nature.com)
  • Similarly, other forms of SED, such as SED with brachydactyly and SED tarda Namaqualand type (NSED), have been recognized and classified under the International Nomenclature and Classification of the Osteochondrodysplasias. (medscape.com)
  • Type II collagen is a primary matrix protein of physeal and epiphyseal cartilage. (medscape.com)
  • The reported cases suggest the condition is hereditary and is transmitted as an autosomal recessive trait. (orpha.net)
  • A group of researchers and clinicians including Edwin M. Stone, Robert Folberg, and Jay H. Krachmer mapped granular type I, granular type II, and lattice dystrophy to chromosome 5q in 1994 (4). (uiowa.edu)
  • With the increasing molecular definition of several types of collagen and recognition of the concentration of certain types in cartilage tissue, many skeletal dysplasias came to be defined as collagen abnormalities. (medscape.com)
  • With the increasing molecular definition of several types of collagen and recognition of the concentration of certain types in cartilage tissue, many skeletal dysplasias have now been defined as collagen abnormalities. (medscape.com)