Idiopathic osteoporosis of childhood or adolescence without blue sclerae and other stigmata of osteogenesis imperfecta is occasionally observed and sometimes more than one sib is affected. This condition, which may be a distinct recessively inherited entity, was delineated by Dent and Friedman (1965) and was reviewed by Dent (1969). The condition described by Chowers et al. (1962) may fall into this category, but the presence of amino aciduria and low serum uric acid makes a renal tubular defect of the Fanconi type likely. Marder et al. (1982) demonstrated low plasma calcitriol (1,25-dihydroxycholecalciferol) and normal serum calcifediol (25-hydroxycholecalciferol) in a 12-year-old girl with idiopathic juvenile osteoporosis. Deficiency of calcitonin has been suspected in cases of IJO, but exogenous calcitonin, in the experience of Jackson et al. (1988), had no benefit.

A number sign (#) is used with this entry because of evidence that susceptibility to early-onset autosomal dominant osteoporosis can be conferred by heterozygous mutation in the WNT1 (164820) gene on chromosome 12q13. Clinical Features Keupp et al. (2013) described a 4-generation family segregating early-onset osteoporosis and fractures inherited in an autosomal dominant pattern. Affected family members showed recurrent fractures (e.g., of vertebrae and ribs after minor trauma) beginning in adolescence, low-bone-turnover markers, and a reduction of trabecular and cortical bone as revealed by high-resolution CT. Mapping Laine et al. (2013) performed a genomewide microsatellite linkage analysis with the use of DNA from 10 affected and 6 healthy members of a Finnish family segregating autosomal dominant early-onset osteoporosis and identified one putative linkage area of 25.5 Mb on chromosome 12 that included the WNT1 gene. Molecular Genetics By whole-exome sequencing of 2 affected individuals from a 4-generation family segregating autosomal dominant early-onset osteoporosis and fractures, Keupp et al. (2013) identified a heterozygous missense mutation in the WNT1 gene (R235W; 164820.0007) that segregated with the phenotype in the family.

Idiopathic juvenile osteoporosis (IJO) is a primary condition of bone demineralization that presents with pain in the back and extremities, walking difficulties, multiple fractures, and radiological evidence of osteoporosis. Epidemiology The exact prevalence is unknown but several hundreds of cases have been reported in the literature so far. Clinical description Onset usually occurs in the prepubertal period, between 8 and 12 years of age. The first sign of IJO is usually pain in the lower back, hips and feet. Knee and ankle pain, kyphosis, loss of height and a sunken chest may also be present.

Juvenile osteoporosis is a condition of bone demineralization characterized by pain in the back and extremities, multiple fractures, difficulty walking, and evidence of osteoporosis . Symptoms typically develop just before puberty. Osteoporosis is rare in children and adolescents. When it does occur, it is usually caused by an underlying medical disorder or by medications used to treat the disorder. This is called secondary osteoporosis . Sometimes, however, there is no identifiable cause of osteoporosis in a child. This is known as idiopathic osteoporosis . There is no established medical or surgical therapy for juvenile osteoporosis.

Evans syndrome is a very rare autoimmune disorder in which the immune system destroys the body's red blood cells, white blood cells and/or platelets. Affected people often experience thrombocytopenia (too few platelets) and Coombs' positive hemolytic anemia (premature destruction of red blood cells). Signs and symptoms may include purpura , paleness, fatigue , and light-headedness. The exact cause of this condition is unknown. The best treatment options for Evans syndrome depend on many factors, including the severity of the condition; the signs and symptoms present; and each person's response to certain therapies.

A rare chronic hematologic disorder characterized by the simultaneous or sequential association of autoimmune hemolytic anemia (AIHA; a disorder in which auto-antibodies are directed against red blood cells causing anemia of varying degrees of severity) with immune thrombocytopenic purpura (ITP; a coagulation disorder in which auto-antibodies are directed against platelets causing hemorrhagic episodes) and occasionally autoimmune neutropenia, in the absence of a known underlying etiology. Epidemiology The prevalence in Europe is estimated at 1/1,000,000 but there are no robust epidemiological data available. Clinical description The syndrome can manifest both in childhood or adulthood. Episodes of thrombocytopenia may precede, occur concurrently with (50% of cases), or follow episodes of AIHA. The severity of symptoms and the delay between episodes of AIHA and/or ITP is variable.

Oculoauricular syndrome, Schorderet type is a rare, genetic developmental defect during embryogenesis syndrome characterized by various ophthalmic anomalies (including congenital microphthalmia, microcornea, cataract, anterior segment dysgenesis, ocular coloboma and early onset rod-cone dystrophy) and abnormal external ears (low-set pinna with crumpled helix, narrow intertragic incisures, abnormal bridge connecting the crus of the helix and the antihelix, narrow external acoustic meatus, and lobule aplasia).

Oculoauricular syndrome Oculoauricular syndrome is inherited in an autosomal recessive manner. Specialty Medical genetics Oculoauricular syndrome is a rare genetic condition affecting the eyes and ears. It is due to mutations in the H6 family homeobox 1 (HMX1) gene. It is also known as the Schorderet-Munier-Franceschetti syndrome. Contents 1 Signs and symptoms 1.1 Eyes 1.2 Ears 2 Genetics 3 Pathogensis 4 Diagnosis 4.1 Differential diagnosis 5 Epidemiology 6 History 7 References 8 External links Signs and symptoms [ edit ] The clinical features of this condition are as follows: [ citation needed ] Eyes [ edit ] microphthalmia coloboma nystagmus corneal sclerosis cataract glaucoma anterior synechiae posterior synechiae macular hypoplasia rod-cone dystrophy divergent strabismus posterior embryotoxon Ears [ edit ] malformed pinnae low-set pinnae crumpled helix narrow external acoustic meatus coloboma of the lobules Hearing is normal Genetics [ edit ] This condition is inherited in an autosomal recessive manner. The gene responsible is located on the short arm of chromosome 4 (4p16.1) [1] Pathogensis [ edit ] This is not presently understood. [ citation needed ] Diagnosis [ edit ] Differential diagnosis [ edit ] This includes Morning glory syndrome [ citation needed ] Epidemiology [ edit ] This condition has only been described in three families to date (2017). [ citation needed ] History [ edit ] This condition was first described in 1945. [2] The gene responsible was identified in 2008. [1] References [ edit ] ^ a b Schorderet, D.F.; Nichini, O.; Boisset, G.; Polok, B.; Tiab, L.; Mayeur, H.; Raji, B; de la Houssaye, G; Abitbol, M.M.; Munier, FL (2008).

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder that occurs in females and mainly affects the reproductive system. This condition causes the vagina and uterus to be underdeveloped or absent, although external genitalia are normal. Affected women usually do not have menstrual periods due to the absent uterus. Often, the first noticeable sign of MRKH syndrome is that menstruation does not begin by age 16 (primary amenorrhea). Women with MRKH syndrome have a female chromosome pattern (46,XX) and normally functioning ovaries.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome describes a spectrum of Mullerian duct anomalies characterized by congenital aplasia of the uterus and upper 2/3 of the vagina in otherwise phenotypically normal females. It can be classified as either MRKH syndrome type 1 (corresponding to isolated utero-vaginal aplasia) or MRKH syndrome type 2 (utero-vaginal aplasia associated with other malformations) (see these terms). Epidemiology MRKH syndrome has a worldwide incidence of 1/4500 live female births. Clinical description MRKH syndrome is most often diagnosed in adolescence as the first symptom is usually a primary amenorrhea in young women presenting otherwise with normal development of secondary sexual characteristics and normal external genitalia. MRKH syndrome type 1 and 2 patients lack the uterus and the upper 2/3 of the vagina leading to difficulties with sexual intercourse in some.

To date, two population-based nationwide studies have been conducted both estimating a prevalence about 1 in 5,000 live female births. [ contradictory ] [22] [23] According to some reports, Queen Amalia of Greece may have had the syndrome, but a 2011 review of the historical evidence concludes that it is not possible to determine the inability of her and her husband to have a child. [24] [6] Their inability to conceive an heir contributed to the overthrow of the king King Otto . [24] People with MRKH [ edit ] Ben Barres , transgender male scientist [25] Esther Morris Leidolf , medical sociologist and intersex activist Shon Klose , Australian intersex activist and musician [26] [27] Jaclyn Schultz , Miss Michigan [28] Suspected cases [ edit ] Amalia of Oldenburg [29] See also [ edit ] MURCS association Cervical agenesis Vaginal hypoplasia WNT4 deficiency SERKAL syndrome Regenerative medicine References [ edit ] ^ "Müllerian Agenesis: Diagnosis, Management, and Treatment" . ... Retrieved 2019-10-27 . ^ One Plus One: Shon Klose , Australian Broadcasting Corporation, 2015-09-28 , retrieved 2019-10-27 ^ "Why This Woman Is Proud to Be Known as "The Pageant Queen Without a Uterus " " .

Overview Giant cell arteritis is an inflammation of the lining of your arteries. Most often, it affects the arteries in your head, especially those in your temples. For this reason, giant cell arteritis is sometimes called temporal arteritis. Giant cell arteritis frequently causes headaches, scalp tenderness, jaw pain and vision problems. Untreated, it can lead to blindness. Prompt treatment with corticosteroid medications usually relieves symptoms of giant cell arteritis and might prevent loss of vision.

Giant cell arteritis (GCA) is a large vessel vasculitis predominantly involving the arteries originating from the aortic arch and especially the extracranial branches of the carotid arteries. Epidemiology GCA is the most common adulthood vasculitis with an annual incidence of 1/3,000-1/25,000 adults over 50 years old. It is more frequent in populations of northern European background. GCA affects people of more than 50 years old (median age at diagnosis between 70-75 years old) and occurs twice as frequently in women as in men. Clinical description GCA often starts insidiously with general symptoms, cranial manifestations (headache, jaw claudication, scalp tenderness, visual loss), and, in about 50% of patients, polymyalgia rheumatica. Visual symptoms due to an ischemic optic neuropathy occur in 20-30% of patients, and can rapidly lead to irreversible monocular blindness.

Giant cell arteritis (GCA) is a form of vasculitis , a group of disorders that cause inflammation of blood vessels. GCA most commonly affects the arteries of the head (especially the temporal arteries, located on each side of the head), but arteries in other areas of the body can also become inflamed. The inflammation causes the arteries to narrow, resulting in poor blood flow. Signs and symptoms when arteries in the head are involved may include a throbbing headache on one side or the back of the head, tenderness of the scalp, flu-like symptoms, and/or problems with eyesight. Symptoms when other arteries are involved depend on the location of those arteries.

For a general phenotypic description and a discussion of genetic heterogeneity of primary open angle glaucoma (POAG), see 137760. Wiggs et al. (2004) identified 25 pedigrees with typical juvenile-onset primary open angle glaucoma (JOAG), demonstrating autosomal dominant inheritance. They sequenced the myocilin gene (MYOC; 601652) in probands from each family and found mutations in 8%. To identify novel genes responsible for JOAG, they used families that did not have myocilin mutations for a genomewide screen. Multipoint linkage analysis of chromosome 9 markers achieved a peak hlod score of 4.0 between markers D9S1803 and D9S196 on chromosome 9q22.

For a general phenotypic description and a discussion of genetic heterogeneity of primary open angle glaucoma (POAG), see 137760. Clinical Features Wang et al. (2006) reported a 3-generation Chinese family in which 8 members had confirmed autosomal dominant juvenile-onset primary open angle glaucoma (JOAG; see 137750). Age at diagnosis ranged from 12 to 32 years. All of those affected showed notable increase in intraocular pressure and severe visual loss. All had a wide anterior chamber. Although most of them had typical glaucoma changes in optic disc and visual field, they all showed a normal iris, no anterior segment anomalies, and corneal thickness and anterior chamber depth within normal ranges. Mapping In 8 affected members of a Chinese family segregating autosomal dominant JOAG, Wang et al. (2006) excluded mutations in the MYOC (601652), OPTN (602432), and WDR36 (609669) genes.

For a general phenotypic description and a discussion of genetic heterogeneity of open angle glaucoma (POAG), see 137760. Mapping Wiggs et al. (2004) identified 25 pedigrees with typical juvenile-onset OAG (JOAG), demonstrating autosomal dominant inheritance. They sequenced the myocilin gene (MYOC; 601652) in probands from each family and found mutations in 8%. To identify novel genes responsible for JOAG, they used families that did not have myocilin mutations for a genomewide screen. Multipoint linkage analysis of chromosome 20 markers achieved a peak hlod score of 4 between markers D20S189 and D20S104 on chromosome 20p12.

A number sign (#) is used with this entry because of evidence that one form of primary open angle glaucoma (POAG), designated GLC1A, is caused by heterozygous mutation in the MYOC gene (601652) on chromosome 1q. Heterozygous mutations in the CYP1B1 gene (601771) may also contribute to the phenotype by digenic inheritance. For a general phenotypic description and a discussion of genetic heterogeneity of POAG, see 137760. Clinical Features Impressive 'dominant' pedigrees of juvenile glaucoma were reported by Stokes (1940), Allen and Ackerman (1942), and others. In a Scottish family that settled in Virginia, Courtney and Hill (1931) described 18 cases (10 males, 8 females) in 5 generations with 2 instances of failure of penetrance in the third generation.

A primary early-onset glaucoma that is characterized by early onset, severe elevation of intra ocular pressure of rapid progression, leading to optic nerve excavation and, when untreated, substantial visual impairment. Epidemiology The disorder is estimated to occur in 0,32/100 000 individuals before the age of 20 years. Clinical description Juvenile glaucoma (JG) typically presents between the ages of 5 to 18 years, but it can appear later. Patients are initially asymptomatic and are often discovered incidentally on a routine examination. JG is generally bilateral; there can be a marked asymmetry between the two eyes.

Isolated patella aplasia-hypoplasia is an extremely rare genetic condition characterized by congenital absence or marked reduction of the patellar bone described in only a few families to date.

A number sign (#) is used with this entry because of evidence that familial candidiasis-9 (CANDF9) is caused by homozygous mutation in the IL17RC gene (610925) on chromosome 3p25. For a general description and a discussion of genetic heterogeneity of familial candidiasis, see CANDF1 (114580). Clinical Features Ling et al. (2015) reported 3 unrelated patients with isolated recurrent chronic mucocutaneous candidiasis infections from early childhood. Symptoms included chronic and recurrent oral thrush and impetigo, sometimes with nail involvement. None of the patients had recurrent viral or bacterial infections, or other fungal infections.

A number sign (#) is used with this entry because of evidence that familial candidiasis-6 (CANDF6) is caused by heterozygous mutation in the IL17F gene (606496) on chromosome 6p12. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of familial candidiasis, see CANDF1 (114580). Molecular Genetics Puel et al. (2011) investigated a multiplex family from Argentina with autosomal dominant inheritance of chronic cutaneous candidiasis. No mutations were identified in the IL22 (605330), IL22RA (605457), IL10RB (123889), IL17RA (605461), IL17RC (610925), or IL17A (603149) genes. However, Puel et al. (2011) detected a heterozygous ser65-to-leu mutation in the IL17F gene in the index case (606496.0001).

A number sign (#) is used with this entry because familial candidiasis-4 (CANDF4) is caused by homozygous mutation in the DEC1 (CLEC7A) gene (606264) on chromosome 12p13. For a general description and a discussion of genetic heterogeneity of familial chronic candidiasis, see CANDF1 (114580). Clinical Features Ferwerda et al. (2009) studied a nonconsanguineous Caucasian family of Dutch ancestry in which 2 sisters had recurrent vulvovaginal candidiasis and onychomycosis. Another sister and their mother had chronic onychomycosis, whereas their father had only transient onychomycosis, with a relatively late age at onset and complete recovery. Microbiologic assessment of the nails of the 3 sisters revealed growth of Trichophyton rubrum.

Description Chronic mucocutaneous candidiasis (CMC) includes a group of rare disorders with altered immune responses, selective against Candida, characterized by persistent and/or recurrent infections of the skin, nails, and mucous membranes, caused by organisms of the genus Candida, mainly Candida albicans (Zuccarello et al., 2002). Isolated familial chronic mucocutaneous candidiasis is distinct from candidiasis with endocrinopathy (240300). In myeloperoxidase deficiency (254600), susceptibility to candidiasis may be increased. Genetic Heterogeneity of Candidiasis Familial candidiasis-1 (CANDF1) maps to chromosome 2p. CANDF2 (212050) is caused by mutation in the CARD9 gene (607212) on chromosome 9q34.3.

In a 9-year-old girl with chronic mucocutaneous candidiasis and cutaneous anergy, Snyderman et al. (1973) found that mononuclear leukocytes failed to migrate in vitro toward two chemotactic stimuli, leukocyte-derived chemotactic factor and C5A. After treatment with transfer factor, the patient's monocytes responded to both chemotactic factors. There is no information on the genetics of this presumably genetic disorder, but autosomal recessive inheritance is a reasonable presumption. Deficiency of leukocyte myeloperoxidase has been found with disseminated candidiasis (254600). In other cases chronic mucocutaneous candidiasis has been related to a deficiency of lymphokine (247650) or a defect in lymphocyte transformation that either is intrinsic (247450) or results from inhibition by a serum factor (247430).

A number sign (#) is used with this entry because of evidence that immunodeficiency-51 (IMD51) is caused by homozygous mutation in the IL17RA gene (605461) on chromosome 22q11. Description Immunodeficiency-51 is an autosomal recessive primary immune deficiency that is usually characterized by onset of chronic mucocutaneous candidiasis in the first years of life. Most patients also show recurrent Staphylococcal skin infections, and may show increased susceptibility to chronic bacterial respiratory infections. Patient cells show a lack of cellular responses to stimulation with certain IL17 isoforms, including IL17A (603149), IL17F (606496), IL17A/F, and IL17E (IL25; 605658) (summary by Levy et al., 2016). Clinical Features Puel et al. (2011) investigated a French child, born to first-cousin parents of Moroccan descent, who presented with Candida albicans dermatitis during the neonatal period and displayed Staphylococcus aureus dermatitis at 5 months of age.

Chronic mucocutaneous candidiasis can have many causes, e.g., (1) failure of lymphocytes to transform in response to antigen, either because of an intrinsic defect (247450) or because of an inhibiting serum factor (247430); (2) failure of production of lymphokine; or (3) unresponsiveness of monocytes to lymphokine (252250). Deficient production of lymphokine despite normal lymphoblastic transformation was demonstrated by Lehner et al. (1972). Inheritance - Autosomal recessive Lab - Failure of production of lymphokine - Normal lymphoblastic transformation Skin - Chronic mucocutaneous candidiasis ▲ Close

For a general description and a discussion of genetic heterogeneity of familial candidiasis, see CANDF1 (114580). Clinical Features Zuccarello et al. (2002) described a Sicilian kindred in which 11 individuals in 5 generations had an apparently distinctive form of familial chronic candidiasis characterized by early-onset infections caused by different species of Candida restricted to the nails of the hands and feet and associated with low serum concentration of intercellular adhesion molecule-1 (ICAM1; 147840). Inheritance The pedigree pattern in the family reported by Zuccarello et al. (2002) was consistent with either autosomal recessive inheritance or autosomal dominant inheritance with incomplete penetrance. Zuccarello et al. (2002) favored the latter possibility, even though the pedigree contained a few marriages between consanguineous relatives. Mapping By genomewide scan of the family reported by Zuccarello et al. (2002), Mangino et al. (2003) assigned the chronic mucocutaneous candidiasis (CANDF3) locus to a 19-cM pericentromeric region on chromosome 11 (multipoint lod score of 3.52 between markers D11S1312 and D11S4191).

Acyl-CoA oxidase deficiency Other names ACOX1 deficiency Acyl CoA oxidase enzyme Specialty Medical genetics Acyl-CoA oxidase deficiency is a rare disorder that leads to significant damage and deterioration of nervous system functions ( neurodegeneration ). [1] It is caused by pathogenic variants in ACOX1 , which codes for the production of an enzyme called peroxisomal straight-chain acyl-CoA oxidase (ACOX1). [1] This specific enzyme is responsible for the breakdown of very long chain fatty acids (VLCFAs) . [2] Defective function of the ACOX1 enzyme prevents proper breakdown of these VLCFAs, leading to accumulation and interference with the nervous system. [1] [2] Acyl-CoA oxidase deficiency affects a person from birth, and most newborns affected with this condition will not survive past early childhood. [1] Affected individuals can be born with hypotonia , seizures, and dysmorphic features, such as widely spaced eyes, a low nasal bridge and low set ears. Polydactyly and hepatomegaly have also been described. [1] Most babies will learn to walk and begin speaking, before experiencing a rapid decline in motor function between the ages of 1 and 3. [3] As the person ages, and the conditions worsens, they begin to experience exaggerated reflexes ( hyperreflexia ), more severe and frequent seizures, and gradual loss of vision and hearing. [1] [2] There is no cure for this condition, however there are a range of symptom-based treatments, used to provide supportive care. Contents 1 Signs and symptoms 2 Genetics 3 Diagnosis 4 Treatment 5 References 6 External links Signs and symptoms [ edit ] Children are born with this condition and their symptoms can be seen immediately. [2] In the early stages these can appear quite mild; weak muscle tone (often extreme hypotonia), lack of neonatal reflexes , seizures and abnormal (dysmorphic) facial features such as widely spaced eyes, a low nasal bridge, low set ears and an abnormally large forehead. [1] [2] Due to the nature of the disease, in the build-up of VLCFAs, symptoms worsen progressively over time. [4] Children can often reach the stage at which they begin to walk and talk, before experiencing a rapid decline in motor skills due to demyelination and subsequent nerve damage. [2] [3] A hearing deficit may develop, eyesight and response to visual and physical stimuli begins to diminish and eventually becomes non-existent. [1] [2] The life expectancy of an individual with ACOX1 deficiency is 5 years. [2] [3] Genetics [ edit ] Acyl-CoA oxidase deficiency is an autosomal recessive disorder that is caused by biallelic pathogenic variants in ACOX1. [1] [5] This is the gene that codes for the production of an enzyme called peroxisomal straight-chain acyl-CoA oxidase which is responsible for the breakdown of VLCFAs. [1] [2] It is not completely clear how the build-up of these VLCFAs causes the symptoms seen with this condition, however research suggests that this abnormal accumulation triggers an inflammation in the nervous system which leads to demyelination . [1] Demyelination leads to the loss of white matter, leukodystrophy , in the brain and spinal cord. [1] [5] It is this leukodystrophy that is related to the development of neurological abnormalities in people with Acyl-CoA oxidase deficiency. [5] Acyl-CoA oxidase deficiency is an extremely rare condition. [1] Diagnosis [ edit ] Diagnosis can be done both prenatally based on family history and after birth based on clinical suspicion. [1] [5] The primary prenatal diagnosis techniques involve the assessment of amniotic fluid for an abnormal elevation in VLCFAs, and a reduced presence (or in some cases complete absence) of acyl-CoA oxidase in fibroblasts . If the causative variants in a family are known, prenatal diagnosis can be performed by molecular testing. [4] After birth, there are a number of diagnostic techniques available for use. A blood sample can be taken, from which the serum levels of VLCFAs and acyl-CoA oxidase activity can be assessed.

Peroxisomal acyl-CoA oxidase deficiency is a disorder that causes deterioration of nervous system functions (neurodegeneration) beginning in infancy. Newborns with peroxisomal acyl-CoA oxidase deficiency have weak muscle tone (hypotonia) and seizures. They may have unusual facial features, including widely spaced eyes (hypertelorism), a low nasal bridge, and low-set ears. Extra fingers or toes (polydactyly ) or an enlarged liver (hepatomegaly) also occur in some affected individuals. Most babies with peroxisomal acyl-CoA oxidase deficiency learn to walk and begin speaking, but they experience a gradual loss of these skills (developmental regression), usually beginning between the ages of 1 and 3.

Neurologic regression occurred at age 28 months, and she showed severe hypotonia, dysphagia, hyperreflexia of the lower limbs, extensor plantar responses, and retinal degeneration. ... The mean age of developmental regression was 28 months, and the mean age at death was 5 years.