Children with hyper igm syndrome have frequent sinus and lung infections. The hyper igm syndromes are a group of rare inherited immune deficiency disorders characterized by impairment of immunoglobulin isotype switching resulting from defects in the cd40 ligandcd40 signaling pathway. Xlinked hyper igm syndrome omim 308230 is a genetic immunodeficiency syndrome that presents with bacterial and opportunistic infections from an early age. Affected individuals may develop autoimmune disorders, neurologic complications from brain and spinal cord central nervous system infections, liver disease, and gastrointestinal tumors. Clinical features and genetic analysis of 20 chinese patients with. Other forms of hyper igm syndrome are inherited as autosomal recessive traits and have been observed in females and males. In boys, failure to express cd40 ligand on tcells can be demonstrated. Higm can thus be associated with an impairment of both bcell and tcell activation. Russellsilver syndrome is a growth disorder characterized by slow growth before and after birth. The hyperigm syndrome is a rare immune deficiency disorder which was first described in 1961 in two independent reports by rosen and colleagues and by burtin. Xlinked hyper igm syndrome xlhigm, the most frequent. Jun 26, 2017 hyper igd syndrome is the less severe form of a metabolic disorder known as mevalonate kinase deficiency. In the absence of known causes for primary or secondary immunodeficiency, possible causes could include measles, pertussis and post infectious complications of pulmonary. Symptoms often become apparent early during infancy or childhood.
Hyper igm syndrome is a type of primary immunodeficiency syndrome. People with this disorder have abnormal levels of proteins called antibodies or immunoglobulins. In this type, b cells cannot receive the signal from t cells to switch classes. Hyperigm syndrome is characterized by normal or high levels of immunoglobulin m igm and decreased levels or absence of other immunoglobulins. Primary immunodeficiency occurs when part of a persons immune system is missing or does not work correctly. Hyper igm syndrome is a primary immunodeficiency pid which should be managed and followed closely by an immunologist with experience treating pids. There may be other mutations in other genes that are not known at this time.
Hyperigm syndrome type 2 higm2 is a rare immunodeficiency characterized by normal or elevated serum igm levels with absence of igg, iga, and ige, resulting in a profound susceptibility to bacterial infections. It is caused by the lack of heavy chain classswitching from igm to other isotypes. The hyper igm syndrome higm is one of the rarest primary immunodeficiencies. Hyper igm syndrome patients with the hyper igm syndrome have an inability to switch their antibody immunoglobulin production from igm to igg, iga, and ige. One would expect opportunistic infections in any immunodeficiency syndrome. They concluded that the genetics of the hyper igm syndrome is still unresolved. This signs and symptoms information for hyper igm syndrome 3 has been gathered from various sources, may not be fully accurate, and may not be the full list of hyper igm syndrome 3 signs or hyper igm syndrome 3 symptoms. They usually have very low levels of both immunoglobulin a iga and immunoglobulin g igg. Yes are approved or conditionally approved by new york state and do not require an nys npl exemption. Genetic tests to detect specific mutations can be done in specialized laboratories. The bodies of people with primary immunodeficiency cant get rid of germs or protect themselves from new germs as well as they should. Hyper igm syndrome medigoo health medical tests information.
Probable autosomal dominant inheritance of one form was suggested. Xlinked hyperigm syndrome only affects males, as the defective gene is located on the x chromosome. Inheritance patterns genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. It is considered an autoinflammatory disease, with recurrent episodic or chronic unexplained inflammation, characterized by periodic episodes of fever, and other symptoms such as joint pain, swollen lymph nodes, skin rash, headaches, and abdominal pain. Hyper igm syndrome is a very rare disease that affects only 1 in 1,000,000 individuals. Furthermore, signs and symptoms of hyper igm syndrome may vary on an individual basis for each patient. For a discussion of genetic heterogeneity of immunodeficiency with hyperigm, see higm1.
Unlike xlinked hyper igm syndrome or hyper igm syndrome type 3, which affect both the t cell and b cell systems, these two forms of the disorder only affect the b cell system. Wiskottaldrich syndrome genetics home reference nih. Hyper igm syndromes is a group of primary immune deficiency disorders characterized by. Hyper igm syndrome is characterized by normal or high levels of immunoglobulin m igm and decreased levels or absence of other immunoglobulins.
There is a type of hyper ige syndrome, which runs in families due to mutations in gene on chromosome 4. Xlinked hyper igm syndrome genetics home reference nih. It is inherited from the mother who is an asymptomatic carrier. Mutation of the cd40l gene in xlinked hyperigm syndrome. Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. Hyper igm syndrome type 2 is estimated to affect fewer than 1 in 1,000,000 people in the general population. Hyperigm syndrome type 4 with a b lymphocyteintrinsic selective deficiency in ig classswitch recombination article pdf available in journal of clinical investigation 1121. Individuals with wiskottaldrich syndrome have microthrombocytopenia, which is a decrease in the number and size of. The autosomal recessive forms of hyper igm syndrome are extremely rare. Mitogen proliferation may be normal, but nk and tcell cytotoxicity are frequently impaired. In terms of treatment for hyper igm syndrome, there is the use of allogeneic hematopoietic cell transplantation. Pdf hyperigm syndrome type 4 with a b lymphocyteintrinsic.
Practice mendelian inheritance of immunodeficiency disorders with khan academys free online exercises. Aug 01, 20 a collection of disease information resources and questions answered by our genetic and rare diseases information specialists for immunodeficiency with hyper igm type 1. Clinical and molecular features of xlinked hyper igm syndrome. Immunodeficiency with hyper igm him is a rare primary immunodeficiency characterized by the production of normal to increased amounts of igm antibody of questionable quality and an inability to produce sufficient quantities of igg and iga. Life expectancy of people with hyper igm syndrome and recent progresses and researches in hyper igm syndrome. The more common of the two, known as xlinked hyperigm syndrome xhim, is caused by an abnormal gene on the x chromosome and affects only boys. Hyper igm syndrome type 3 characterized by mutations of the cd40 gene. The invitae hyper igm syndrome panel analyzes up to 6 genes which are associated with hyper igm syndromes. Xlinked hyperigm syndrome xhigm is one type of primary. Hyper igm syndrome is an immunoglobulin ig deficiency characterized by normal or elevated serum igm levels and decreased levels or absence of other serum immunoglobulins, resulting in susceptibility to bacterial infections. What is the life expectancy of someone with hyper igm. Antigenspecific responses may be decreased or absent. Hyper igm syndrome switch or not to switch request pdf.
Unlike other hyper igm syndromes, the type 2 patients identified thus far did not present with a history of opportunistic infections. Hyperigm syndrome higm seattle cancer care alliance. Cd40 ligand is expressed on activated t lymphocytes and is necessary for t cells to induce b cells to undergo immunoglobulin. There are seven main subtypes of higm and the most frequent is xlinked higm, resulting from cd40l. Hyper igm syndrome type 5 characterized by mutations of the ung gene.
May 31, 2007 xlinked hyper igm syndrome higm1, a disorder of abnormal t and bcell function, is characterized by low serum concentrations of igg and iga and normal or elevated serum concentrations of igm. The most common and the most clinically severe of these is an xlinked deficiency in cd40 ligand cd40 l. Xlinked recessive inheritance is a mode of inheritance in which a mutation in a gene on the x chromosome causes the phenotype to be expressed 1 in males who are necessarily hemizygous for the gene mutation because they have only one x chromosome and 2 in females who are homozygous for the gene mutation i. Although there are several treatments that can help maintain a generally healthy status quo, the comorbidity and general outcomes vary within the patient population. A novel homozygous mutation in recombination activating gene 2 in. Some people with xlinked hyper igm syndrome have low levels of white blood cells called neutrophils neutropenia. Analysis of these genes may confirm a diagnosis of hyper igm syndrome in individuals with recurrent respiratory or opportunistic infections and normal to increased levels of immunoglobulin m igm, and low igg and iga.
Diagnosis is usually made before the age of 12 months when the male infant presents with unusual or severe infections. We report a novel mutation of the cd40l gene in xlinked hyperigm syndrome xhigm in two sibling chinese patients, about which we made a literature. As a result, people are more susceptible to bacterial infections. These mutations reflected the heterogeneity of cd40l gene and. Hyper igm syndrome type 2 higm2 is a rare immunodeficiency characterized by normal or elevated serum igm levels with absence of igg, iga, and ige, resulting in a profound susceptibility to bacterial infections. The influence of cd40cd154 interactions on the expressed human v h repertoire. Approximately 70% of people with hyper igm syndrome inherit the disorder in an. Hyper igm syndrome is a very rare disease that affects only 1 in 1,000,000. There are two forms of hyperigm syndrome, defined by their patterns of inheritance. Hyper igm syndrome, which is characterized by the presence of normal or elevated serum levels of igm and low igg and iga, may be caused by one of at least 10 gene defects table 17. Hyper igm syndromes are a group of rare disorders in which the immune system. Hyper igm syndrome higm is a descriptive term that reflects a common laboratory abnormality high serum igm level with low serum iga and igg levels found in several otherwise dissimilar types of immunodeficiencies table 925. It is also sometimes called the eczemathrombocytopeniaimmunodeficiency syndrome in keeping with aldrichs original description in 1954.
Hyperigm syndrome higm, him, xlinked immunodeficiency. As a result, patients with this disease have decreased levels of igg and iga but normal or elevated levels of igm in their blood. This observation led to the interest ing speculation of a common process regulating il2 and cd40l gene transcription farrington et al. Babies with this condition have a low birth weight and often fail to grow and gain weight at the expected rate failure to thrive. The severity of xlinked hyper igm syndrome varies among affected individuals, even among members of the same family. Wiskottaldrich syndrome is characterized by abnormal immune system function immune deficiency, eczema an inflammatory skin disorder characterized by abnormal patches of red, irritated skin, and a reduced ability to form blood clots. Introduction the initial terminology of hyper igm syndrome is really xlinked immunodeficiency with hyper immunoglobulin m xhigm or higm1 is a rare form of primary immunodeficiency disease caused by mutations in the gene that codes for cd40 ligand cd40l, also known as cd154 and gp39. Mar 10, 20 hyper igm syndrome immunologic phenotype presenting with low igg, iga, and ige levels with normal or increased igm levels the term hyper igm is a misnomer igm levels are not necessarily high the relative excess of igm is due to a defect in class switch recombination csr in certain cases somatic hypermutation shm is also affected uygungil. Digeorge syndrome is a condition present from birth that can cause a range of lifelong problems, including heart defects and learning difficulties. Connect with other hyper igm patients support the foundation. The putative genetic lesion is in the aicda gene found at 12p. Autosomal dominant hyper ige syndrome nord national. Hyper igm syndrome type 4 a defect in class switch recombination downstream of the aicda gene that does not impair somatic hyper mutation. Diagnosis of hyper igm syndrome is suspected in patients with low or absent igg or iga and normal or elevated igm antibodies.
Encyclopedia of genetics, genomics, proteomics and informatics. Hyper igm syndrome higm, him, xlinked immunodeficiency with hyper igm. What is the life expectancy of someone with hyper igm syndrome. This signs and symptoms information for hyper igm syndrome has been gathered from various sources, may not be fully accurate, and may not be the full list of hyper igm syndrome signs or hyper igm syndrome symptoms. The hyper igm syndromes are a group of rare inherited immune deficiency disorders. The disorder is characterized by repeated bacterial infections of the skin and lungs pneumonia, skeletal abnormalities, and characteristic facial features. Russellsilver syndrome genetics home reference nih. Advanced research in primary immunodeficiency diseases by the indian council. Pcp is one of the most frequent and severe opportunistic infections in people with weakened immune systems. This makes it hard for them to fight off infections and illness. See also overview of immunodeficiency disorders and approach to the. Infection pneumocystis pneumonia pcp, which is common in infants with hyper igm syndrome, is a serious illness. Hyper ige syndrome is an immune deficiency caused by a genetic mutation in either stat3 autosomal dominant, also known as jobs syndrome or dock8 autosomal recessive.
Xlinked recessive inheritance psychology wiki fandom. Hyper igm syndrome type 4 which is a defect in class switch recombination downstream of the aicda gene that does not impair somatic hypermutation. The most likely diagnosis of hyper igm syndrome was made but screening for cd40 ligand cd154 was normal. If you have questions or want more information about genetic testing for hyper igm syndrome, ask your doctor or genetic counselor. Hyper igm syndrome is an xlinked genetic disorder more commonly affecting males than females. The term primary means that the disorder is present from birth, in contrast to secondary immunodeficiencies such as aids, which are acquired later in life by previously healthy persons. It is the most common form of hyper igm syndrome, accounting for approximately 70% of cases. Hyperigm syndrome merck manuals professional edition. Immunodeficiency with hyperigm higm results from genetic defects in the cd40cd40 ligand cd40l pathway or in the enzymes required for immunoglobulin class switch recombination and somatic hypermutation. Hyperigd syndrome genetic and rare diseases information.
Hyperigm syndrome a case report and a clinical perspective. Hyper igd syndrome is the less severe form of a metabolic disorder known as mevalonate kinase deficiency. For a discussion of genetic heterogeneity of immunodeficiency with hyper igm, see higm1 308230. Xlinked immunodeficiency with hyper immunoglobulin m xhigm or higm1 is a rare form of primary immunodeficiency disease caused by mutations in the gene that codes for cd40 ligand cd40l, also known as cd154 and gp39. Hyperigm syndrome higm is a disorder that can be passed on from parent to child genetic. Patients with higm syndrome have an inability to switch from the production of antibodies of the igm type to antibodies of the igg, iga or ige types. Immunodeficiency with hyper igm type 1 genetic and rare.
Many cd40 ligand deficiency are first diagnosed after having pcp in their first year of life. Mendelian inheritance of immunodeficiency disorders. Hyper igm syndrome an overview sciencedirect topics. Inheritance can be autosomal dominant or autosomal recessive.
Xlinked hyper igm syndrome higm1, a disorder of abnormal t and bcell function, is characterized by low serum concentrations of igg and iga and normal or elevated serum concentrations of igm. Lurie childrens hospital of chicago, northwestern university feinberg school of medicine, chicago, il, usa. Oct 23, 2019 xlinked immunodeficiency with hyper immunoglobulin m xhigm or higm1 is a rare form of primary immunodeficiency disease caused by mutations in the gene that codes for cd40 ligand cd40l, also known as cd154 and gp39. As a result, patients have decreased levels of igg and iga and normal or elevated levels of igm. Autosomal dominant hyper ige syndrome adhies is a rare multisystem primary immunodeficiency disorder. Hyperigm syndrome is also known as hypogammaglobulinemia with hyper igm. Hyperigm syndrome type 5 characterized by mutations of the ung gene. By definition, xlinked hyper igm syndrome higm1 is inherited in an. A number of different genetic defects can cause the hyper igm syndrome. In addition, cd40 ligand is important for other tlymphocyte functions, and therefore, patients with xlinked hyper igm syndrome xhim also have a defect in some of the protective functions of their tlymphocytes. You may search for a genetic counselor in your area using an online address book. Give possible reasons for bronchiectasis developing in childhood. This kind of hyper ige syndrome is acquired by autosomal dominant inheritance whereby if one of the parents is affected, then chances of passing the abnormal gene to the child is about 50%. Wiskottaldrich syndrome was is a rare xlinked recessive disease characterized by eczema, thrombocytopenia low platelet count, immune deficiency, and bloody diarrhea secondary to the thrombocytopenia.
Sporadic cases of hyperigm syndrome have been noted in girls and in occasional pedigrees, suggest ing autosomal recessive inheritance notarangelo et al. The other forms of hyper igm syndrome have only been described in the medical literature in a very small number of people. Hyper igm syndrome definition hyper igm syndrome is a primary immunodeficiency disorder in which the childs body fails to produce certain specific types of antibodies. Xlinked hyper igm syndrome is a condition that affects the immune system and occurs almost exclusively in males. What is xlinked hyper igm syndrome xlinked hyper igm syndrome omim 308230 is a genetic immunodeficiency syndrome that presents with bacterial and opportunistic infections from an early age. People with higm do not have enough of the most efficient infectionfighting antibodies. In medicine, hyper igm syndrome type 2 is a rare disease unlike other hyper igm syndromes, the type 2 patients identified thus far did not present with a history of opportunistic infections. Antonio condinoneto from the 2019 idf national conference. Despite the name, high levels of igm are inconsistently found in all forms of hyper igm syndrome. For a discussion of genetic heterogeneity of immunodeficiency with hyper igm. Many patients with autosomal dominant stat3 hyperige syndrome have characteristic facial and dental abnormalities, fail to lose their primary teeth, and have two sets of teeth simultaneously. It is characterized by a defect in immunoglobulin isotype switching resulting in low or undetectable serum levels of igg, iga and ige but normal or elevated igm levels.
386 750 267 1284 1016 1547 1047 637 644 720 321 278 242 494 1134 188 402 289 1349 979 1431 1176 1180 817 1028 1232 1134 573 1316 873 1134 1298 1308 359 902 267 1177 200