In an early classification of EDS, the designations EDS I and EDS II were used for severe and mild forms of classic EDS, respectively. ... EDS II had all the stigmata of EDS I, but to a minor degree (summary by Steinmann et al., 2002). ... The criterion used to distinguish EDS II from EDS I was the absence of widened atrophic scars in EDS II. ... Ten patients each were analyzed with classic EDS, vascular EDS (130050), hypermobility EDS (130020), and TNX-deficient EDS (606408). ... In the Villefranche classification of EDS (Beighton et al., 1998), 6 main descriptive types were substituted for earlier types numbered with Roman numerals: classic type (EDS I and EDS II, 130010), hypermobility type (EDS III, 130020), vascular type (EDS IV, 130050), kyphoscoliosis type (EDS VI, 225400), arthrochalasia type (EDS VIIA and VIIB, 130060), and dermatosparaxis type (EDS VIIC, 225410).
., R134C, 120150.0059) cause classic EDS. Description The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders that share the common features of skin hyperextensibility, articular hypermobility, and tissue fragility. ... There are both severe and mild forms of classic EDS, previously designated EDS I and EDS II, respectively. ... The criterion used to distinguish EDS II from EDS I was the absence of widened atrophic scars in EDS II. De Felice et al. (2001) studied 4 patients with EDS II and 8 patients with EDS III (130020), the hypermobile type. ... Overall, over 90% of patients fulfilling all major Villefranche criteria for classic EDS were shown to harbor a type V collagen defect, indicating that this is the major, if not the only, cause of classic EDS.
Ehlers-Danlos syndrome, classic type (cEDS) is a form of Ehlers-Danlos syndrome that affects the connective tissue and is characterized by skin hyperextensibility, widened atrophic scars and joint hypermobility.
Classical Ehlers-Danlos syndrome (EDS) is a genetic connective tissue disorder that is caused by defects in a protein called collagen. ... More than 90% of people with classical EDS have mutations in COL5A1 or COL5A2, two genes which encode type V collagen.
Overlap with osteogenesis imperfecta may be observed resulting in an EDS/osteogenesis imperfecta overlap phenotype. Diseases in this group include classical Ehlers-Danlos syndrome (EDS), musculocontractural EDS, hypermobile EDS, vascular EDS, arthrochalasia EDS, dermatosparaxis EDS, periodontal EDS, X-linked EDS, brittle cornea syndrome, classical-like EDS type 1 and type 2, cardiac-valvular EDS, spondylodysplastic EDS, myopathic EDS, and kyphoscoliotic EDS.
Atrophic scar in a case of EDS Translucent skin in vascular EDS Individual with EDS displaying skin hyperelasticity Piezogenic papules on the heel of an individual with hypermobile EDS Cardiovascular Thoracic outlet syndrome Arterial rupture Valvular heart disease, such as mitral valve prolapse, creates an increased risk for infective endocarditis during surgery. ... There are special recommendations for anesthesia in people with EDS. Detailed recommendations for anesthesia and perioperative care of people with EDS should be used to improve safety. Surgery in people with EDS requires careful tissue handling and a longer immobilization afterward. Prognosis The outcome for individuals with EDS depends on the specific type of EDS they have. ... Severe mobility-related disability is seen more often in hypermobile EDS than in classical EDS or vascular EDS. Although all types of EDS are potentially life-threatening, most people have a normal lifespan. ... The most commonly occurring is hypermobile EDS, followed by classical EDS. ... Animals with the condition should not be bred, as the condition can be inherited. Animal EDSEDS in a dog Same dog with EDSEDS in same dog showing an atrophic scar St Bernard (dog) with Ehlers-Danlos-like syndrome showing hyperextensible skin Degenerative suspensory ligament desmitis (DSLD) is a similar condition seen in many breeds of horses.
Ehlers-Danlos syndrome is a group of disorders that affect connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. Defects in connective tissues cause the signs and symptoms of these conditions, which range from mildly loose joints to life-threatening complications. The various forms of Ehlers-Danlos syndrome have been classified in several different ways. Originally, 11 forms of Ehlers-Danlos syndrome were named using Roman numerals to indicate the types (type I, type II, and so on). In 1997, researchers proposed a simpler classification (the Villefranche nomenclature) that reduced the number of types to six and gave them descriptive names based on their major features.
Nomenclature Kyphoscoliotic EDS (kEDS) was initially referred to as EDS, oculoscoliotic form after its first description by Pinnell et al . Prior to the development of the 1998 Villefranche classification, kEDS was known as EDS VI (or EDS VIA). ... In 2017, the International EDS Consortium proposed a revised EDS classification system. The new nomenclature for EDS, kyphoscoliotic form is kyphoscoliotic EDS, or kEDS [Malfait et al 2017]. ... Kyphoscoliotic Ehlers-Danlos syndrome (kEDS) has some overlapping clinical features with other forms of EDS, particularly classic EDS and vascular EDS.
Previously, two subtypes, EDS type I and EDS type II, differing only in phenotypic severity, were recognized; it is now apparent that they form a continuum of clinical findings. ... Nomenclature As a result of the 1997 Villefranche conference on EDS [Beighton et al 1998], the former EDS type I and type II were reclassified as EDS, classic type. In 2017, the International EDS Consortium proposed a revised EDS classification system. The new nomenclature for EDS, classic type is classic EDS, or cEDS [Malfait et al 2017]. ... For recommendations on treatment of joint laxity and dislocations, see Hypermobile EDS.
Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue disorders caused by abnormalities in the structure, production, and/or processing of collagen. ... The signs and symptoms of EDS vary by type and range from mildly loose joints to life-threatening complications. ... Mutations in a variety of genes may lead to EDS; however, the underlying genetic cause in some families is unknown. Depending on the subtype, EDS may be inherited in an autosomal dominant or an autosomal recessive manner. There is no specific cure for EDS. The treatment and management is focused on preventing serious complications and relieving associated signs and symptoms.
Clinical Features Wenstrup et al. (2002) performed a prospective cohort study on 71 consecutive EDS patients. ... Wenstrup et al. (2002) concluded that aortic root dilatation is a common finding in EDS. ... Ten patients each were analyzed with classic EDS (130000), vascular EDS (130050), hypermobility EDS, and TNX-deficient EDS (606408). ... Patients with the hypermobility type EDS caused by TNXB haploinsufficiency were least affected. ... The disorder in this family is here classified as a nonvascular variant of EDS IV.
None of these features is specific to EDS, and these features alone are insufficient to establish a diagnosis of any type of EDS [Malfait et al 2017]. Establishing the Diagnosis The diagnostic criteria for hEDS (and all other types of EDS) were revised by the International EDS Consortium in 2017 [Malfait et al 2017]. ... Among those with independently confirmed EDS, Chiari malformation was found in only one (4.7%) of 21 individuals with hypermobile EDS [Castori et al 2010a] and one (5.5%) of 18 individuals with headache and unspecified types of EDS [Jacome 1999]. ... The other forms of EDS are distinguished by additional connective tissue manifestations [Malfait et al 2017]: Classic EDS (cEDS) includes skin and soft tissue fragility. ... In vascular EDS (vEDS), the joint laxity is predominantly in small joints, as opposed to the generalized laxity typically observed in hypermobile EDS.
It is generally considered the least severe form of Ehlers-Danlos syndrome (EDS) although significant complications can occur. ... Although hypermobile EDS is thought to be a genetic condition, the exact underlying cause is unknown in most cases. ... Most cases of hypermobile EDS, are inherited in an autosomal dominant manner.
Clinical Features Cole et al. (1986) reported a 3-month-old girl with type VII EDS. ... The changes were more pronounced than those observed in EDS VIIB (EDSARTH2; 617821), but less severe than those present in EDS VIIC (EDSDERMS; 225410). ... A patient with EDS VIIA had a more severe phenotype compared to those with EDS VIIB, and electron microscopy indicated a more severe disruption of collagen fibrils in EDS VIIA compared to EDS VIIB. ... Nusgens et al. (1992) referred to the 2 structural defects of procollagen polypeptides as EDS VIIA and EDS VIIB for the COL1A1 and COL1A2 defects, respectively. They used the designation EDS VIIC for the autosomal recessive enzymatic form (225410).
Description Arthrochalasia-type EDS is distinguished from other types of EDS by the frequency of congenital hip dislocation and extreme joint laxity with recurrent joint subluxations and minimal skin involvement (Byers et al., 1997; Giunta et al., 2008). For a discussion of genetic heterogeneity of arthrochalasia-type EDS, see 130060. ... Eyre et al. (1985) and Steinmann et al. (1985) each reported a similar case of EDS VII. ... The authors suggested that the last feature may be more common in EDS VII than previously realized. ... Carr et al. (1994) reported a 32-year-old woman with EDS VIIB confirmed by genetic analysis (120160.0032).
Ehlers-Danlos syndromes (EDS) form a heterogeneous group of hereditary connective tissue diseases characterized by joint hyperlaxity, cutaneous hyperelasticity and tissue fragility. ... Etiology Arthrochalasic EDS is due to abnormal maturation of the alpha1 (I) (former type VIIA) or alpha2 (I) (former type VIIB) collagen I pro-chains, in which the aminoterminal propeptide is incorrectly cleaved. ... Genetic counseling Arthrochalasic EDS is transmitted as an autosomal dominant trait. Management and treatment Arthrochalasic EDS patients should be managed by specialist teams.
Clinical description The age of onset of ED is 20-30 years (earlier in Asians). ... ED rarely results in blindness, even in patients who suffer vitreous hemorrhages. ... ED has also been associated with several diseases, in particular tuberculosis. However, their role in the pathogenesis of ED is yet to be ascertained. ... Blindness due to ED is rare.
. ^ Comprehensive Ophthalmology, (4th Ed) 2007 by A K Khurana, Professor, Regional Institute of Ophthalmology, Postgraduate Institute of Medical Sciences, Rohtak- 124001, India ^ Eales disease at eMedicine ^ "Eales Disease - an overview | ScienceDirect Topics". www.sciencedirect.com.
Eales disease is a rare vision disorder that appears as an inflammation and white haze around the outercoat of the veins in the retina. This condition is most common among young males and normally affects both eyes. In most cases, vision becomes suddenly blurred because the vitreous, the clear jelly that fills the eyeball behind the lens of the eye, seeps out. Treatment includes corticosteroids in the inflammation stage and photocoagulation in the proliferative stage of the disease. Visual prognosis is good if treatment begins early in the course of the disease.
Although the findings were similar to those of classic EDS, all tenascin-X-deficient patients lacked atrophic scars, a major diagnostic criteria for classic EDS. ... Unlike classic EDS patients, they did not have atrophic scarring or poor wound healing. ... Ten patients each were analyzed with classic EDS (see 130000), vascular EDS (130050), hypermobility EDS (130020), and TNX-deficient EDS. Overall, those with classic EDS and TNX-deficient EDS reported the most neuromuscular involvement, with muscle weakness, hypotonia, myalgia, easy fatigability, and intermittent paresthesias, although patients in all groups reported these features. ... Patients with the hypermobility type EDS caused by TNXB haploinsufficiency were least affected.
Ehlers-Danlos syndrome due to tenascin-X deficiency is a type of Ehlers-Danlos syndrome characterized by generalized joint hypermobility, skin hyperextensibility and easy bruising without atrophic scarring. Other common features include foot and hand deformities (piezogenic papules, pes planus, broad forefeet, brachydactyly, and acrogenic skin of hands), severe fatigue and neuromuscular symptoms including muscle weakness and myalgia.
Classical-like Ehlers-Danlos syndrome (EDS due to tenascin-X (TNX) deficiency) is a form of Ehlers Danlos Syndrome (EDS) characterized by an unusually large range of joint movement (hypermobility), skin that is soft, stretchy, and fragile and easy bruising. ... Classical-like EDS is caused by mutations in both copies of the TNXB gene and is inherited in an autosomal recessive manner; however, some individuals with a mutation in only one copy of the TNXB gene can have symptoms similar to EDS hypermobility type including joint hypermobility and soft skin. ... Some individuals with classical-like EDS can have larger deletions of genetic material including other genes. ... There is no cure for classical-like EDS. The treatment and management is focused on preventing serious complications and relieving associated signs and symptoms.
Abnormal Eggs, EDS '76 EDS '76 is one of the important viral diseases of birds, notably chickens, ducks, geese and swans. ... Treatment and Prevention There is no treatment for EDS '76, but there are ways in which chickens can be prevented form being infected by EDS '76. ... Several vaccine are available: Izovac EDS, Nobilis EDS, AVIVAC-EDS-76 and other EDS '76 available vaccines. ... "Egg Drop Syndrome (EDS -'76) in India: Seroprevalence of EDS -'76 Virus Infections in Poultry Flocks". ... External links EDS at The Poultry Site
References ^ a b c Anderson DM, ed. (2003). "Sensitization." Dorland's Illustrated Medical Dictionary, 30th ed. ... ISBN 0-7216-0146-4. ^ a b c Brown MJ, ed. (1992). "Sensitization." Miller-Keane Encyclopedia & Dictionary of Medicine, Nursing, and Allied Health, 5th ed. ... ISBN 0-7216-3456-7. ^ a b Pugh MB, ed. (2000). "Sensitization." Stedman's Medical Dictionary, 27th ed. ... ISBN 0-683-40007-X. ^ a b c Janeway C, Travers P, Walport M, Shlomchik M, eds. (2001). ... Dictionary of Terms in Immunology, 3rd ed. Osaka: Saishin-Igakusha, Ltd., p. 510.
Periodontal EDS (EDSPD; previously designated 'EDS VIII') is a specific subtype of EDS with autosomal dominant inheritance, in which the defining feature is an EDS phenotype combined with severe periodontal inflammation. ... Six main descriptive types were substituted for earlier types numbered with Roman numerals: classic type (EDS I and II), hypermobility type (EDS III), vascular type (EDS IV), kyphoscoliosis type (EDS VI), arthrochalasia type (EDS VIIA and VIIB), and dermatosparaxis type (EDS VIIC). Six other forms were listed, one of which was the periodontitis type (EDS VIII). ... Reinstein et al. (2013) reported a 4-generation family with EDS VIII. ... No pathogenic mutations in C1R or C1S were identified in 71 patients with aggressive periodontitis but no EDS-like features, or in 11 patients clinically diagnosed with vascular EDS.
In the second family (family 17), the proband was a 75-year-old man with features of periodontal EDS including thin, fragile, and hyperelastic skin, easy bruising, atrophic scars, pretibial discoloration, and scoliosis.
Ehlers-Danlos syndromes (EDS) form a heterogeneous group of hereditary connective tissue diseases characterized by joint hyperlaxity, cutaneous hyperelasticity and tissue fragility. Clinical description EDS type VIII is the rarest form of EDS and is characterized by severe early-onset periodontal disease in conjunction with the presence of plaques of scar tissue in the pretibial zones (hyperpigmented atrophic scars).
The abnormality in type III collagen suggested the diagnosis of EDS IV. ... Pope and Nicholls (1983) took a less pessimistic view of pregnancy in EDS IV. ... Germain and Herrera-Guzman (2004) provided an extensive review of EDS IV. ... Ten patients each were analyzed with classic type I EDS (130000), vascular EDS, hypermobility EDS (130020), and TNX-deficient EDS (606408). ... Palmeri et al. (2003) characterized 7 members of a family with EDS IV.
Epidemiology The estimated prevalence of forms of EDS varies between 1/10,000 and 1/25,000, with EDS type IV representing approximately 5 to 10% of cases. ... Etiology EDS type IV is caused by mutations in the COL3A1 gene coding for type III procollagen. ... Genetic counseling EDS type IV is inherited as an autosomal dominant trait. Management and treatment In the absence of a specific treatment for EDS type IV, medical intervention should be focused on symptomatic treatment and prophylactic measures. ... A conservative approach is usually recommended when caring for vascular complications in a patient suffering from EDS type IV.
Six main descriptive types were substituted for earlier types numbered with Roman numerals: classic type (EDS I and II), hypermobility type (EDS III), vascular type (EDS IV), kyphoscoliosis type (EDS VI), arthrochalasia type (EDS VIIA and VIIB), and dermatosparaxis type (EDS VIIC). ... The diagnosis of EDS and studies of skin biopsy material were made when he was 3 months old. ... Nomenclature The kyphoscoliotic type of Ehlers-Danlos syndrome was at one time separated into EDS VIA (with lysyl hydroxylase deficiency) and EDS VIB (with normal lysyl hydroxylase activity). ... EDS VIB is now known as the musculocontractural type of EDS (601776), caused by mutation in the CHST14 gene (608429). ... Might this be the ocular-scoliotic form of EDS VI, rather than type IV?
Common signs and symptoms include hyperextensible skin that is fragile and bruises easily; joint hypermobility; severe hypotonia at birth; progressive kyphoscoliosis (kyphosis and scoliosis); and fragility of the sclera. kyphoscoliosis EDS is caused by changes (mutations) in the PLOD1 gene or the FKBP14 gene and it is inherited in an autosomal recessive manner.
Ehlers-Danlos syndrome, kyphoscoliotic type (EDKT) is a form of Ehlers-Danlos syndrome characterized by severe hypotonia and kyphoscoliosis at birth, generalized joint hyperextensibility and ocular globe fragility.
Spondylodysplastic Ehlers-Danlos syndrome (EDS) is a subtype of the EDS, a group of genetic disorders of the connective tissue, which is the material between body cells that gives tissues form and strength. ... Like people with other types of EDS, people with Spondylodysplastic EDS have unusually flexible joints; loose, elastic skin; and easy scarring. ... Spondylodysplastic EDS may be caused by mutations in the B4GALT7 gene, the B3GALT6, or the SLC39A13 gene.
Ehlers-Danlos syndrome, progeroid type (EDS-PF) is a form of Ehlers-Danlos syndrome characterized by a premature aging with sparse hair, macrocephaly, loose elastic skin, failure to thrive, joint laxity, psychomotor retardation, hypotonia, and defective wound healing with atrophic scars.
Molecular Genetics In 4 patients from 3 families with a progeroid form of EDS who did not have mutations in the B4GALT7 gene, Nakajima et al. (2013) performed Sanger sequencing of the B3GALT6 gene and found that all 4 patients were compound heterozygous for a frameshift and a missense mutation (615291.0007-615291.0011).
Hernandez et al. (1979) reported 2 unrelated male patients with what appeared to be a new variety of EDS. Mental retardation, short stature, wrinkled facies, curly and fine hair, scanty eyebrows and eyelashes, telecanthus, periodontitis, multiple nevi, pectus excavatum, and bilateral cryptorchidism were present in addition to joint hypermobility, hyperextensibility and fragility of skin, papyraceous scars, bruisability, varicose veins, and pes planus--features suggesting a form of EDS.
Some people also have hyperflexible joints and vascular anomalies, which also occur in Ehlers-Danlos syndrome (EDS). ... EDS with periventricular heterotopia, previously considered a variant of EDS, is now considered to be the same as X-linked periventricular heterotopia type 1 (PVNH1) and is not included as an EDS subtype under the 2017 classification of EDS.
Summary Clinical characteristics. FLNA-related periventricular nodular heterotopia (PVNH), a neuronal migration disorder, is characterized by the presence of uncalcified nodules of neurons ectopically situated along the surface of the lateral ventricles. Affected individuals are predominantly heterozygous females; males most often show early lethality. Affected females present with seizures at an average age of 14-15 years; intelligence ranges from normal to borderline. The risk for cardiovascular disease, stroke, and other vascular/coagulation problems appears to be increased. Diagnosis/testing. The diagnosis of FLNA-related PVNH is established by the identification of: Characteristic head MRI findings; and Heterozygous pathogenic variants in FLNA in females or hemizygous pathogenic variants in FLNA in males.
Ectodermal dysplasias (ED) are a group of more than 180 disorders that affect the outer layer of tissue of the embryo (ectoderm) that helps make up the skin, sweat glands, hair, teeth, and nails. Symptoms of ED can range from mild to severe and may include teeth abnormalities; brittle, sparse or absent hair; abnormal fingernails; inability to perspire (hypohidrosis); various skin problems; and other symptoms. Different types of EDs are caused by mutations in different genes, and can be inherited in a variety of ways. No cure currently exist for the different types of ED, but many treatments are available to address the individual symptoms.
Some ED conditions are only present in single family units and derive from very recent mutations. ... Sweat glands Individuals affected by certain ED syndromes cannot perspire. ... In some types of ED, abnormal development of parts of the eye can result in dryness of the eye, cataracts, and vision defects. Professional eye care can help minimize the effects of ED on vision. Similarly, abnormalities in the development of the ear may cause hearing problems. ... Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders.
The term ''ectodermal dysplasia'' defines a heterogeneous group of heritable disorders of the skin and its appendages characterized by the defective development of two or more ectodermal derivatives, including hair, teeth, nails, sweat glands and their modified structures (i.e. ceruminous, mammary and ciliary glands). The spectrum of clinical manifestations is wide and may include additional manifestations from other ectodermal, mesodermal and endodermal structures. Epidemiology Overall prevalence of ectodermal dysplasia syndromes is unknown, but appears rare with a presumed cumulative incidence of approximately 1/1,429. More than 120 clinically and/or genetically distinct ectodermal dysplasias have been cataloged. Clinical description In ectodermal dysplasias, the skin usually appears dry with superficial scaling and proneness to dermatitis.
Sheep medicine (2nd ed.). CRC Press. p. 137. ISBN 9781498700153 . ^ a b Winter, AC (2012). ... A handbook for the sheep clinician (7th ed.). Wallingford: CABI. pp. 92–93. ... In Gyles, CL; Prescott, JF; Songer, JG; Thoen, CO (eds.). Pathogenesis of bacterial infections in animals (4th ed.). ... In Uzal, FA; Songer, JG; Prescott, JF; Popoff, MR (eds.). Clostridial diseases of animals. ... ISBN 9781118728307 . ^ Wood, James, ed. (1907). "Braxy" . The Nuttall Encyclopædia.
EDS was suspected on the basis of blue sclerae and soft, velvety, hyperextensible skin. ... Nusgens et al. (1992) noted that the clinical manifestations of EDS VIIC were different from those of EDS VIIA (130060) and VIIB, in which the clinical picture is dominated by joint laxity and subluxations. The skin fragility EDS VIIC can be as severe as that observed in the dermatosparactic calves. ... In 1, a structural defect in the alpha-2(I) chain was demonstrated, consistent with EDS VIIB. ... Nomenclature Nusgens et al. (1992) referred to this disorder as Ehlers-Danlos syndrome type VIIC, reserving EDS VIIA and EDS VIIB for the disorders resulting from defects in the procollagen alpha-1 and alpha-2 polypeptides, respectively.
Ehlers-Danlos syndromes (EDS) form a heterogeneous group of hereditary connective tissue diseases characterized by joint hyperlaxity, cutaneous hyperelasticity and tissue fragility. The dermatosparaxis type (formerly called EDS type VIIC) is marked by extremely fragile tissues, hyperextensible skin and easy bruising.
Primary Care Medicine: Office Evaluation and Management of the Adult Patient (6th ed.). ... Companion to clinical neurology (2nd ed.). Oxford University Press US. p. 587. ... Neurology in clinical practice. 2 (4th ed.). Taylor & Francis. p. 2074. ... Diagnosis and treatment of symptoms of the respiratory tract (2nd ed.). ... A Clinical Guide to Epileptic Syndromes and Their Treatment (2nd ed.).
(eds.). Veterinary Surgery. London: Elsevier Health Sciences. pp. 1990–1992. ISBN 9780323263375 . ^ Withrow SJ, MacEwen EG, eds. (2001). Small Animal Clinical Oncology (3rd ed.). ... In Schaer, Michael; Gaschen, F (eds.). Clinical medicine of the dog and cat (3rd ed.).
ED can have psychological consequences as it can be tied to relationship difficulties and self-image. ... " Psychological impact ED often has an impact on the emotional well-being of both men and their partners. ... Once inserted, an erection can begin within 10 minutes and last up to an hour. Medications to treat ED may cause a side effect called priapism. Testosterone Men with low levels of testosterone can experience ED. ... The study of ED within medicine is covered by andrology, a sub-field within urology. ... In: UpToDate, Martin KA (Ed), UpToDate, Waltham, MA, 2018. ^ Frederick, LR; Cakir, OO; Arora, H; Helfand, BT; McVary, KT (October 2018).
Ehlers-Danlos syndromes (EDS) form a heterogeneous group of hereditary connective tissue diseases characterized by joint hyperlaxity, cutaneous hyperelasticity and tissue fragility. EDS type V is characterised by hyperextensible skin but tissue fragility and joint hyperlaxity are mild. This form of EDS is very rare and has been described in only two families so far.