The causes of monocytopenia include: acute infections, stress, treatment with glucocorticoids, aplastic anemia, hairy cell leukemia, acute myeloid leukemia, treatment with myelotoxic drugs and genetic syndromes, as for example MonoMAC syndrome. [1] It has been proposed as a measure to predict neutropenia , [2] though some research indicates that it is less effective than lymphopenia . [3] Contents 1 Causes 2 Diagnosis 3 Treatment 4 References 5 External links Causes [ edit ] Some of the causes are: [ citation needed ] - acute infections - stress - treatment with glucocorticoids - aplastic anemia - hairy cell leukemia - acute myeloid leukemia - treatment with myelotoxic drugs - genetic syndromes (e.g.: MonoMAC syndrome) Diagnosis [ edit ] - Blood Test (CBC) (Normal range of Monocytes: 1-10%) (Normal range in males: 0.2-0.8 x 10 3 /microliter) - Blood test checking for monocypenia (Abnormal ranges: <1%) (Abnormal range in males: <0.2 10 3 /microliter) Treatment [ edit ] This section is empty. ... External links [ edit ] Classification D ICD - 9-CM : 288.59 DiseasesDB : 29083 SNOMED CT : 165539005 v t e Diseases of monocytes and granulocytes Monocytes and macrophages ↑ -cytosis : Monocytosis Histiocytosis Chronic granulomatous disease ↓ -penia : Monocytopenia Granulocytes ↑ -cytosis : granulocytosis Neutrophilia Eosinophilia / Hypereosinophilic syndrome Basophilia Bandemia ↓ -penia : Granulocytopenia/agranulocytosis ( Neutropenia / Severe congenital neutropenia / Cyclic neutropenia Eosinopenia Basopenia ) Disorder of phagocytosis Chemotaxis and degranulation Leukocyte adhesion deficiency LAD1 LAD2 Chédiak–Higashi syndrome Neutrophil-specific granule deficiency Respiratory burst Chronic granulomatous disease Neutrophil immunodeficiency syndrome Myeloperoxidase deficiency This article about a disease of the blood or immune system is a stub .
A number sign (#) is used with this entry because the disorder is a contiguous gene syndrome caused by homozygous deletion of approximately 122 kilobases on chromosome 11p15-p14, which contains the genes USH1C (605242), ABCC8 (600509), and KCNJ11 (600937). ... The molecular basis of the disorder was found to be a homozygous deletion of 122 kilobases on chromosome 11p15-p14, including part of the ABCC8 and KCNJ11 genes and overlapping with the Usher syndrome IC (276904) and DFNB18 (602092) loci. ... INHERITANCE - Autosomal recessive GROWTH Other - Failure to thrive HEAD & NECK Ears - Hearing loss, profound congenital sensorineural ABDOMEN Gastrointestinal - Enteropathy - Diarrhea - Intractable vomiting - Feeding problems - Small bowel biopsy shows crypt hyperplastic villus atrophy, inflammatory infiltrate within the lamina propria, and disorganized surface epithelium GENITOURINARY Kidneys - Renal tubular dysfunction ENDOCRINE FEATURES - Hyperinsulinism LABORATORY ABNORMALITIES - Hypoglycemia - Generalized aminoaciduria - Homozygous 122Kb deletion 11p15-p14 MOLECULAR BASIS - Contiguous gene syndrome caused by homozygous deletion of approximately 122Kb on chromosome 11p15-p14 ▲ Close
Mitochondrial encephalomyopathy Specialty Neurology , rheumatology , endocrinology A mitochondrial encephalomyopathy is a form of encephalomyopathy that is associated with a mitochondrial disease . MELAS syndrome Examples include MELAS syndrome and MERRF syndrome . ... External links [ edit ] Classification D ICD - 9-CM : 277.87 MeSH : D017237 v t e Mitochondrial diseases Carbohydrate metabolism PCD PDHA Primarily nervous system Leigh disease LHON NARP Myopathies KSS Mitochondrial encephalomyopathy MELAS MERRF PEO No primary system DAD MNGIE Pearson syndrome Chromosomal OPA1 Kjer's optic neuropathy SARS2 HUPRA syndrome TIMM8A Mohr–Tranebjærg syndrome see also mitochondrial proteins This article about a medical condition affecting the nervous system is a stub .
Many individuals with a mutation of mtDNA display a cluster of clinical features that fall into a discrete clinical syndrome, such as the Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with ragged-red fibers (MERRF), neurogenic weakness with ataxia and retinitis pigmentosa (NARP), or Leigh syndrome (LS). However, considerable clinical variability exists and many individuals do not fit neatly into one particular category, which is well-illustrated by the overlapping spectrum of disease phenotypes (including mitochondrial recessive ataxia syndrome (MIRAS) resulting from mutation of the nuclear gene POLG , which has emerged as a major cause of mitochondrial disease.
Lenz–Majewski syndrome Other names Lenz–Majewski hyperostotic dwarfism (LMHD) [1] Lenz–Majewski syndrome ( LMS ), also known as Lenz–Majewski hyperostotic dwarfism ( LMHD ), is a skin condition characterized by hyperostosis , craniodiaphyseal dysplasia , dwarfism, cutis laxa , proximal symphalangism , syndactyly , brachydactyly , mental retardation, enamel hypoplasia and hypertelorism . [2] : 571 Contents 1 Genetics 2 See also 3 References 4 External links Genetics [ edit ] In 2013, whole-exome sequencing showed that a missense mutation resulting in overactive phosphatidylserine synthase 1 was the cause of LMS, making it the first known human disease to be caused by disrupted phosphatidylserine metabolism. ... "Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome". Nature Genetics . 46 (1): 70–76. doi : 10.1038/ng.2829 . hdl : 10400.4/1596 .
Clinical Features Four unrelated patients were reported with a similar syndrome (Braham, 1969; Macpherson, 1974; Lenz and Majewski, 1974; Kaye et al., 1974; Robinow et al., 1977). ... Majewski (2000) reported follow-up on the original patient with Lenz-Majewski syndrome reported by Lenz and Majewski (1974). ... In addition to most of the recognized manifestations of the syndrome, she had dysgenesis of the corpus callosum, mainly hypoplasia of the splenium but also of the genu, and mild hemispheric white matter atrophy. ... Wattanasirichaigoon et al. (2004) reported a sporadic case of Lenz-Majewski syndrome with newly recognized manifestations including facial palsy, cleft palate, and hydrocephalus developing later in infancy. ... Inheritance All reported cases of Lenz-Majewski syndrome have occurred de novo (Sousa et al., 2014).
Pseudomelanism, also called abundism, is another variant of pigmentation, identifiable by dark spots or enlarged stripes, which cover a large part of the body of the animal, making it appear melanistic. [3] The morbid deposition of black matter, often of a malignant character causing pigmented tumors , is called melanosis . [4] Contents 1 Adaptation 1.1 Industrial melanism 2 In cats 3 In birds 4 In humans 4.1 Peutz–Jeghers syndrome 5 Socio-politics 6 See also 7 References 8 Bibliography Adaptation [ edit ] A melanistic European adder ( Vipera berus ) compared to a normal-colored adder Melanism related to the process of adaptation is called adaptive. ... People from parts of Africa, South Asia , Southeast Asia , and Australia may have very dark skin, but this is not melanism. Peutz–Jeghers syndrome [ edit ] This rare genetic disorder is characterized by the development of macules with Hyperpigmentation on the lips and oral mucosa ( melanosis ), as well as benign polyps in the gastrointestinal tract. [25] Socio-politics [ edit ] Further information: Melanin theory The term melanism has been used on Usenet , internet forums and blogs to mean an African-American social movement holding that dark-skinned humans are the original people from which those of other skin color originate. ... See also [ edit ] Albinism Albino and white squirrels Amelanism Black squirrel Erythrism Heterochromia iridum Leucism Piebaldism Vitiligo Xanthochromism Peutz–Jeghers syndrome Ocular melanosis Melanosis References [ edit ] ^ Morales, E. (1995). ... "Mystery behind labial and oral melanotic macules: Clinical, dermoscopic and pathological aspects of Laugier-Hunziker syndrome" . World Journal of Clinical Cases . 6 (10): 322–334. ... The Linnean . 29 (2): 15 - 22. v t e Pigmentation disorders / Dyschromia Hypo- / leucism Loss of melanocytes Vitiligo Quadrichrome vitiligo Vitiligo ponctué Syndromic Alezzandrini syndrome Vogt–Koyanagi–Harada syndrome Melanocyte development Piebaldism Waardenburg syndrome Tietz syndrome Loss of melanin / amelanism Albinism Oculocutaneous albinism Ocular albinism Melanosome transfer Hermansky–Pudlak syndrome Chédiak–Higashi syndrome Griscelli syndrome Elejalde syndrome Griscelli syndrome type 2 Griscelli syndrome type 3 Other Cross syndrome ABCD syndrome Albinism–deafness syndrome Idiopathic guttate hypomelanosis Phylloid hypomelanosis Progressive macular hypomelanosis Leukoderma w/o hypomelanosis Vasospastic macule Woronoff's ring Nevus anemicus Ungrouped Nevus depigmentosus Postinflammatory hypopigmentation Pityriasis alba Vagabond's leukomelanoderma Yemenite deaf-blind hypopigmentation syndrome Wende–Bauckus syndrome Hyper- Melanin / Melanosis / Melanism Reticulated Dermatopathia pigmentosa reticularis Pigmentatio reticularis faciei et colli Reticulate acropigmentation of Kitamura Reticular pigmented anomaly of the flexures Naegeli–Franceschetti–Jadassohn syndrome Dyskeratosis congenita X-linked reticulate pigmentary disorder Galli–Galli disease Revesz syndrome Diffuse/ circumscribed Lentigo / Lentiginosis : Lentigo simplex Liver spot Centrofacial lentiginosis Generalized lentiginosis Inherited patterned lentiginosis in black persons Ink spot lentigo Lentigo maligna Mucosal lentigines Partial unilateral lentiginosis PUVA lentigines Melasma Erythema dyschromicum perstans Lichen planus pigmentosus Café au lait spot Poikiloderma ( Poikiloderma of Civatte Poikiloderma vasculare atrophicans ) Riehl melanosis Linear Incontinentia pigmenti Scratch dermatitis Shiitake mushroom dermatitis Other/ ungrouped Acanthosis nigricans Freckle Familial progressive hyperpigmentation Pallister–Killian syndrome Periorbital hyperpigmentation Photoleukomelanodermatitis of Kobori Postinflammatory hyperpigmentation Transient neonatal pustular melanosis Other pigments Iron Hemochromatosis Iron metallic discoloration Pigmented purpuric dermatosis Schamberg disease Majocchi's disease Gougerot–Blum syndrome Doucas and Kapetanakis pigmented purpura / Eczematid-like purpura of Doucas and Kapetanakis Lichen aureus Angioma serpiginosum Hemosiderin hyperpigmentation Other metals Argyria Chrysiasis Arsenic poisoning Lead poisoning Titanium metallic discoloration Other Carotenosis Tar melanosis Dyschromia Dyschromatosis symmetrica hereditaria Dyschromatosis universalis hereditaria See also Skin color Skin whitening Tanning Sunless Tattoo removal Depigmentation Environment portal Ecology portal Earth sciences portal Evolutionary biology portal
Clinical Features Gustavson et al. (1993) described a 'new' X-linked mental retardation syndrome in 7 male children in 6 separate sibships in 2 generations of a family. ... In addition to severe retardation, the syndrome included microcephaly, optic atrophy with severely impaired vision or blindness, severe hearing defect, spasticity, epileptic seizures, restricted movement of the large joints, and death in infancy or early childhood. ... At least two other mental retardation syndromes mapped to the same region: Borjeson syndrome (301900) and Pettigrew syndrome (304340).
A rare, genetic, X-linked syndromic intellectual disability disorder characterized by severe intellectual disability, microcephaly, post-natal growth retardation, severe visual impairment or blindness (due to optic atrophy), severe hearing defect, spasticity, epileptic seizures, restricted large-joint movements and early death (in infancy or early childhood).
Somatostatinoma (SSoma) is an extremely rare pancreatic neuroendocrine tumor or duodenal endocrine tumor (see these terms) that originates either in the pancreas (50%) or the gastrointestinal tract (50%) and mainly presents with non-specific symptoms of abdominal pain, weight loss, jaundice and diarrhea but, in approximately 20% of pancreatic cases, leads to a somatostatin hypersecretion syndrome (somatostatinoma syndrome) characterized by diabetes mellitus, cholelithiasis, steatorrhea and hypochlorhydria. ... Most SSomas present with non-specific symptoms of abdominal pain, weight loss, painless obstructive jaundice and diarrhea. Somatostatinoma syndrome occurs in those with a functioning pancreatic SSoma with manifestations including diabetes mellitus, cholelithiasis, diarrhea, weight loss, steatorrhea and hypochlorhydria. ... Etiology Some SSomas are components of familial endocrine tumor syndromes. The cause of sporadic SSomas is not clear. SSoma hypersecretes stomatostatin, which inhibits the secretion of numerous gastrointestinal hormones (such as gastrin, secretin, insulin, glucagon, and cholecystokinin), resulting in somatostatinoma syndrome
Cluster of cancer-related symptoms Trotter's syndrome is a cluster of symptoms associated with certain types of advanced nasopharyngeal carcinoma . ... Van Hassel HJ, Topping JW (July 1977). "Trotter's syndrome. A review". Oral Surg. Oral Med.
Syndromic microphthalmia, type 5 is characterized by the association of a range of ocular anomalies (anophthalmia, microphthalmia and retinal abnormalities) with variable developmental delay and central nervous system malformations. ... Pituitary dysfunction, leading to growth hormone deficiency and short stature, or combined pituitary hormone deficiency (CPHD), has also been reported. Etiology The syndrome is caused by heterozygous mutations in the OTX2 gene (14q22.3).
A number sign (#) is used with this entry because of evidence that microphthalmia with associated features (MCOPS5), including pituitary dysfunction, is caused by heterozygous mutation in the OTX2 gene (600037) on chromosome 14q22. There is also evidence that early-onset retinal dystrophy with or without pituitary dysfunction is caused by heterozygous mutation in the OTX2 gene. Nomenclature The term 'anophthalmia' has been misused in the medical literature. True or primary anophthalmia is rarely compatible with life; in such cases, the primary optic vesicle has stopped developing and the abnormal development involves major defects in the brain as well (Francois, 1961). The diagnosis can only be made histologically (Reddy et al., 2003; Morini et al., 2005; Smartt et al., 2005), but this is rarely done.
Specific disorders in this spectrum include: Fibroadipose hyperplasia (also called fibroadipose overgrowth) CLOVES syndrome Megalencephaly-capillary malformation syndrome (MCAP syndrome) Hemihyperplasia‐multiple lipomatosis syndrome (HHML syndrome) Hemimegalencephaly Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face) Signs and symptoms of PROS depend on the specific disorder present.
PIK3CA-related overgrowth spectrum (PROS) is an umbrella term for rare syndromes characterized by malformations and tissue overgrowth caused by somatic mutations in PIK3CA gene. [1] [2] [3] In PROS diseases individuals malformations are seen in several different tissues such as skin, vasculature, bones, fat and brain tissue depending on the specific disease. Contents 1 PROS spectrum diseases 2 Pathophysiology 3 Treatment 4 References PROS spectrum diseases [ edit ] PROS spectrum diseases include: Fibroadipose hyperplasia or Overgrowth Hemihyperplasia Multiple Lipomatosis Congenital Lipomatous Overgrowth Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal (CLOVES) syndrome Macrodactyly Facial Infiltrating Lipomatosis Megalencephaly - Capillary Malformation Dysplastic Megalencephaly Klippel-Trenaunay syndrome Pathophysiology [ edit ] PIK3CA gene codes for p110α protein which is a catalytic subunit of phosphoinositide 3-kinase , a major regulator of several important cellular functions such as cell proliferation, growth and apoptosis. [4] Mutations in PIK3CA cause over-activity of PI3K which in turn leads to altered growth of cells and tissues which is thought to be important for overgrowth and malformations in PROS. [5] Different presentations of PROS diseases are likely explained by acquisition of the mutation in different time points and different cell types during embryonic development [5] Treatment [ edit ] Treatment of PROS diseases is variable and depends on the specific disease. ... Sclerotherapy can be used to treat vascular malformations . [5] In CLOVES syndrome experimental medical therapy using PIK3CA inhibitor, BYL719 , has been reported to be effective to relieve pain and diminish the malformations. [6] References [ edit ] ^ "PIK3CA-related overgrowth spectrum" . rarediseases.info.nih.gov . ... "Targeted therapy in patients with PIK3CA-related overgrowth syndrome". Nature . 558 (7711): 540–546. doi : 10.1038/s41586-018-0217-9 .
Schimke et al. (1971) described a girl who excreted about 100 mg of acid mucopolysaccharide daily, and showed a nonprogressive form of nephrotic syndrome with proteinuria and a defect of cellular immunity. ... A first cousin had no immunodeficiency, but showed a mucolipidosis-like phenotype. GU - Nephrotic syndrome Radiology - Demineralized bones Inheritance - Autosomal recessive Immune - Immunodeficiency - IgA deficiency Misc - Disseminated herpetic infection Lab - Chondroitin-6-sulfaturia - Acid mucopolysacchariduria - Proteinuria Growth - Short stature - Low birth weight - Truncal shortening Liver - Macronodular cirrhosis Cardiac - Cor pulmonale HEENT - Corneal opacities Pulmonary - Severe pulmonary disease ▲ Close
Griffiths et al. (1983) suggested that neurofibromatosis, pheochromocytoma, and duodenal carcinoid constitute a distinct and specific multiple endocrine neoplasia syndrome. They suggested that it might be termed MEN IIIa, with MEN IIIb being assigned to the von Hippel-Lindau syndrome (193300) with pheochromocytoma and islet cell tumors.
Leprechaunism is a congenital form of extreme insulin resistance (a group of syndromes that also includes Rabson-Mensenhall syndrome, type A insulin-resistance syndrome, and acquired type B insulin-resistance syndrome; see these terms) characterized by intrauterine and mainly postnatal severe growth retardation. ... Biologically, episodes of hypo- and hyperglycemia are observed along with marked hyperinsulinemia due to an extreme resistance to insulin. Etiology The syndrome is associated with homozygous or compound heterozygous mutations in the insulin receptor gene ( INSR ; 19p13.3-p13.2).
A number sign (#) is used with this entry because Donohue syndrome is caused by homozygous or compound heterozygous mutation in the insulin receptor gene (INSR; 147670) on chromosome 19p13. ... Elfin facial appearance, growth retardation, severely diminished subcutaneous adipose tissue stores, decreased muscle mass, hypertrichosis, pachyderma, and acanthosis nigricans were cited as notable clinical features. See Seip syndrome (269700). Elsas et al. (1985) stated that 31 patients with leprechaunism had been reported since the original description by Donohue (1948). ... In all 3 cell lines studied, EGF-stimulated receptor autophosphorylation was also decreased, whereas EGF internalization and degradation were normal. The type A syndrome of insulin resistance and acanthosis nigricans showed no abnormality of EGF receptor. ... In affected members of a Yemeni family segregating Donahue syndrome, Hone et al. (1994) identified homozygosity for a substitution of methionine for isoleucine at codon 119 (exon 2) in the INSR gene. ... Nomenclature Fernhoff (2004) noted that Donohue syndrome is a more appropriate designation for this disorder because 'leprechaunism' may be viewed as pejorative by families.
Leprechaunism is a congenital (present from birth) condition characterized by extreme insulin resistance , pre- and postnatal growth delays, characteristic facial features, skin abnormalities, muscular hypotrophy (reduced muscle mass) and enlarged external genitalia in both males and females. The condition is caused by mutations in the insulin receptor gene ( INSR ) gene. It is inherited in an autosomal recessive manner.
Aicardi-Goutieres syndrome is an inherited disease that mainly affects the brain, immune system, and the skin. ... There are several types of Aicardi-Goutieres syndrome, depending on the gene that causes the condition: TREX1 , RNASEH2A , RNASEH2B , RNASEH2C , SAMHD1 , ADAR and IFIH1 , genes.
A number sign (#) is used with this entry because of evidence that Aicardi-Goutieres syndrome-7 (AGS7) is caused by heterozygous mutation in the IFIH1 gene (606951) on chromosome 2q24. Description Aicardi-Goutieres syndrome-7 is an autosomal dominant inflammatory disorder characterized by severe neurologic impairment. ... For a phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750). Clinical Features Rice et al. (2014) reported 8 children with a neurodevelopmental disorder associated with inflammatory markers. ... Adang et al. (2018) described 3 patients with AGS7 who had typical features of syndrome but also presented with pulmonary hypertension, 1 at age 16 years, 1 at 7 years, and 1 at 1 month of age. ... Adang et al. (2018) reported 3 new AGS7 patients with typical features of Aicardi-Goutieres syndrome and, additionally, pulmonary hypertension.
Although this autosomal recessive syndrome showed phenotypic overlap with Aicardi-Goutieres syndrome, Kumar et al. (1998) raised the question of whether it represented a distinct disorder. ... Commenting, Aicardi and Goutieres (2000) highlighted the similarity to Aicardi-Goutieres syndrome and suggested that immune system dysfunction may form part of the Aicardi-Goutieres syndrome phenotype. ... Crow et al. (2004) reported 3 children from 2 families with Aicardi-Goutieres syndrome. All 3 had congenital glaucoma. ... Rice et al. (2007) described a child with classic Aicardi-Goutieres syndrome who was the child of nonconsanguineous Scottish parents. ... Haaxma et al. (2010) reported a second patient with Aicardi-Goutieres syndrome and a de novo heterozygous TREX1 mutation (D18N; 606609.0007).
A number sign (#) is used with this entry because of evidence that Aicardi-Goutieres syndrome-6 (AGS6) is caused by homozygous or compound heterozygous mutation in the ADAR gene (146920) on chromosome 1q21. ... For a phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750). Clinical Features Rice et al. (2012) reported 10 families with 14 children, including 1 set of identical twins, with Aicardi-Goutieres syndrome. ... Molecular Genetics By whole-exome sequencing in 4 probands with a diagnosis of Aicardi-Goutieres syndrome in whom mutations in known causative genes had been excluded, Rice et al. (2012) identified compound heterozygous or homozygous mutations in the ADAR1 gene.
A number sign (#) is used with this entry because of evidence that Aicardi-Goutieres syndrome-2 (AGS2) is caused by homozygous or compound heterozygous mutation in the gene encoding subunit B of ribonuclease H2 (RNASEH2B; 610326) on chromosome 13q14. For a general phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750). Clinical Features Ali et al. (2006) reported 17 children from 8 families with progressive neurodegeneration and encephalopathy beginning at birth or in infancy. ... Mapping By genomewide linkage analysis of 10 families with Aicardi-Goutieres syndrome in whom linkage to AGS1 was excluded, Ali et al. (2006) identified a putative disease locus, termed AGS2, on chromosome 13q14-q21 (maximum multipoint lod score of 5.75 at marker D13S768).
A number sign (#) is used with this entry because Aicardi-Goutieres syndrome-5 (AGS5) is caused by homozygous or compound heterozygous mutation in the SAMHD1 gene (606754) on chromosome 20q11. For a phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750). Clinical Features Rice et al. (2009) reported 13 probands with Aicardi-Goutieres syndrome. ... Molecular Genetics By genomewide linkage analysis and candidate gene sequencing of multiple families with Aicardi-Goutieres syndrome, Rice et al. (2009) identified homozygous or compound heterozygous mutations in the SAMHD1 gene (see, e.g., 606754.0001-606754.0007).
An inherited, subacute encephalopathy characterised by the association of basal ganglia calcification, leukodystrophy and cerebrospinal fluid (CSF) lymphocytosis. Epidemiology Just over 120 cases have been reported in the literature so far. Clinical description The majority of affected infants are born at full term with normal growth parameters. Onset occurs within the first few days or month of life with severe, subacute encephalopathy (feeding problems, irritability and psychomotor regression or delay) associated with epilepsy (53% of cases), chilblain skin lesions on the extremities (43% of cases) and episodes of aseptic febrile illness (40% of cases). Symptoms progress over several months (with the development of microcephaly and pyramidal signs) before the disease course stabilises.
A number sign (#) is used with this entry because of evidence that Aicardi-Goutieres syndrome-3 (AGS3) is caused by homozygous mutation in the gene encoding subunit C of ribonuclease H2 (RNASEH2C; 610330) on chromosome 11q13. Description Aicardi-Goutieres syndrome is an autosomal recessive disorder characterized by onset of encephalopathy in the first year of life following normal early development. ... For a general phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750). Clinical Features Vogt et al. (2013) reported 2 Pakistani sisters who were variably affected with AGS3. ... Mapping Crow et al. (2006) performed genomewide linkage analysis on 6 consanguineous families with Aicardi-Goutieres syndrome and mapped the disease locus, which they termed AGS3, to a 4.9-cM interval on chromosome 11q13.2 between markers D11S4205 and D11S987 (maximum lod score of 4.54). ... Inheritance Crow et al. (2006) demonstrated that Aicardi-Goutieres syndrome-3 is an autosomal recessive disorder.
A number sign (#) is used with this entry because Aicardi-Goutieres syndrome-4 (AGS4) is caused by homozygous or compound heterozygous mutation in the gene encoding subunit A of ribonuclease H2 (RNASEH2A; 606034) on chromosome 19p13. For a phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750). Clinical Features Sanchis et al. (2005) described 2 brothers, born of second-cousin parents of white Spanish ancestry, who had intrauterine growth retardation and clinical features suggestive of intrauterine infection but with negative bacteriologic and serologic investigations. ... Mapping In 2 Spanish brothers with Aicardi-Goutieres syndrome and their second-cousin parents, Sanchis et al. (2005) performed genotype analysis across the AGS1 critical interval. ... Molecular Genetics In 2 brothers with Aicardi-Goutieres syndrome from a consanguineous family of Spanish ancestry reported by Sanchis et al. (2005), Crow et al. (2006) identified a homozygous mutation in the RNASEH2A gene (606034.0001).
Harati et al. (1984) suggested that the family reported by Babbitt et al. (1969) had Cockayne syndrome (216400). An apparently recessive form of basal ganglia calcification was associated with steatorrhea and mental retardation in 4 of 16 sibs in a family reported by Cockel et al. (1973). ... Many of the features were consistent with Miller-Dieker syndrome (247200), except for the calcification and normal chromosome 17. Burn et al. (1986) concluded that the Norman-Roberts syndrome (257320) and the disorders in the patients described by Aicardi and Goutieres (1984) and Baraitser et al. (1983) were different. On the other hand, Reardon et al. (1994) concluded that the disorder in the family of Burn et al. (1986) was the same as pseudo-TORCH syndrome (251290). Billard et al. (1989) reported 14 cases of childhood-onset encephalopathy with calcification of the basal ganglia and proposed a 4-group classification based on a review of the literature.
Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical disability. ... Nomenclature The microcephaly-intracranial calcification syndrome (MICS; also known as pseudo-TORCH syndrome or Baraitser-Reardon syndrome) was previously differentiated from AGS on the basis of congenital microcephaly and the presence of non-neurologic abnormalities including elevation of liver enzymes, hepatomegaly, and thrombocytopenia at birth [Reardon et al 1994]. ... The microcephaly-intracranial calcification syndrome (MICS). Given the phenotype of early-onset Aicardi-Goutières syndrome (AGS) cases (see Clinical Characteristics) [Reardon et al 1994], it is likely that most cases of MICS are in fact AGS (see Nomenclature). ... Hoyeraal Hreidarsson syndrome presents in the first months of life with microcephaly, cerebellar hypoplasia, and intracerebral calcifications. ... Thus, these individuals may have an undefined syndrome within the group of infants with encephalopathy and intracranial calcifications.