Hyper igm syndrome is a very rare disease that affects only 1 in 1,000,000 individuals. It is now recognized that other common manifestations include eczema, mucocutaneous candidiasis, and several connective tissue and skeletal abnormalities. Xlinked hyper igm syndrome higm1, a disorder of abnormal t and bcell function, is characterized by low serum concentrations of igg, iga, and ige with normal or elevated serum concentrations of igm. It is the most common form of hyperigm syndrome, accounting for approximately 70% of cases. 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. Jun 26, 2017 hyper igd syndrome is the less severe form of a metabolic disorder known as mevalonate kinase deficiency.
N2 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. Hyperige recurrent infection syndrome 2, autosomal. Episodes usually last 4 to 6 days and may be triggered by physiologic stress, such as vaccination or minor trauma. The clinical course of xlinked hyper igm syndrome is similar to that of xlinked brutontype agammaglobulinemia except for a greater frequency of autoimmune hematologic disorders neutropenia, hemolytic anemia, thrombocytopenia. 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. The diagnosis of hyper igm syndrome can be done via the following methods and tests. Proliferation of igmproducing plasma cells may lead to. Hyperigm 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.
Hyper igm syndrome is an immunodeficiency disease that results from an. Since the autosomal recessive forms of higm require that the gene on both chromosomes be affected, they are less frequent than the xlinked conditions. Xlinked hyper igm xhigm and nemo with immunodeficiency are inherited as xlinked recessive disorders and only boys are affected. 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.
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 is a type of primary immunodeficiency syndrome. The disorder has autosomal dominant and recessive forms. The igm is not usually as high as is seen in classic hyper igm syndrome. Hyperigm syndrome merck manuals professional edition. Recurrent infections are common in people with this condition. 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. 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. Xlinked hyper igm syndrome omim 308230 is a genetic immunodeficiency syndrome that presents with bacterial and opportunistic infections from an early age. Mendelian inheritance of immunodeficiency disorders.
Xlinked hyper igm xhigm and nemo with immunodeficiency are inherited as xlinked recessive disorders, and only boys are affected. Patients with stat3 hies may have either delay of or failure in shedding of primary teeth. They differ by the nature of underlying genetic defect. Our mission is to improve the treatment, quality of life and the long term outlook for children and adults living with hyper igm through research, support, education, and advocacy to. B essential modulator, while autosomal recessive forms of hyper igm are caused by defects in cd40 or. Idf 2017 national conference session, hyper igm syndrome higm was presented by caroline kou, md on june 16, 2017. Primary immunodeficiency occurs when part of a persons immune system is missing or does not work correctly. The other forms of hyper igm syndrome have only been described in the medical literature in a very small number of people. Xlinked forms of hyper igm are caused by defects in the cd40 ligand gene or nf. A novel homozygous mutation in recombination activating gene 2 in. Hyper igm syndrome is a primary immunodeficiency disorder in which the childs body fails to produce certain specific types of antibodies. The hyperimmunoglobulin m syndromes higm are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination csr, with or without defects of somatic hypermutation shm. Xlinked hyper igm syndrome is a condition that affects the immune system and occurs almost exclusively in males. Manis jp, alt fw 2003 novel antibody switching defects in human patients.
This book contains general medical information and is intended to provide the patient and family with tools to enhance the. For a discussion of genetic heterogeneity of immunodeficiency with. The hyper igm syndromes higm are a group of primary immune. Lurie childrens hospital of chicago, northwestern university feinberg school of medicine, chicago, il, usa. Patients with nemo syndrome may have an elevated igm or iga, but not both. Some patients with higm have now been identified with a novel form of higm that. In terms of treatment for hyper igm syndrome, there is the use of allogeneic hematopoietic cell transplantation. Hyperigm syndrome type 5 characterized by mutations of the ung gene. B essential modulator, while autosomal recessive forms of hyper igm are caused by. Hyper igd syndrome is the less severe form of a metabolic disorder known as mevalonate kinase deficiency.
Hyper igm syndromes is a group of primary immune deficiency disorders characterized by. There are at least four types of autosomal recessive hyper igm syndrome. Cd40 ligand is expressed on activated t lymphocytes and is necessary for t cells to induce b cells to undergo immunoglobulin. Mevalonate kinase deficiency is a spectrum of disease that can range from milder symptoms to severe, even lifethreatening complications. Affected individuals tend to have frequent bouts of pneumonia, which are caused by certain kinds of bacteria that infect the lungs and cause inflammation. This variant of the hyper igm syndrome is caused by mutation of the cd40lg gene. Hyperigm syndrome a case report and a clinical perspective. Hyperigm 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. 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. The hyper igm syndromean evolving story pediatric research. It can involve many different parts of the body and often manifests in different ways in different individuals. Winkelstein, in comprehensive pediatric hospital medicine, 2007. The lesions had increased in number and in size but had not caused any problems with pain, movement, or playing.
Mutation of the cd40l gene in xlinked hyperigm syndrome. Hyperigm syndrome immune disorders msd manual consumer. Mitogen proliferation may be normal, but nk and tcell cytotoxicity can be impaired. Neutropenia responds to ivig and granulocyte colonystimulating factor gcsf. Hyperigd syndrome pediatrics merck manuals professional. Hyperigd syndrome genetic and rare diseases information. The autosomal recessive forms of hyper igm syndrome are extremely rare. Hyper igm syndrome type 5 characterized by mutations of the ung gene. Hyper igm syndrome type 1 higm1 is the xlinked variant of the hyper igm syndrome.
Mevalonate kinase deficiency nord national organization. Hyper igm syndrome immunologic phenotype presenting with low igg, iga, and ige levels with normal or increased igm levels the term hyperigm 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. Hyperigm syndrome type 3 is a form of hyper igm syndrome characterized by mutations of the cd40 gene. Practice mendelian inheritance of immunodeficiency disorders with khan academys free online exercises. Hyperigm higm syndrome is a group of rare, inherited disorders that affect the bodys natural defense immune system. In addition to the susceptibility to pyogenic infections, male patients are prone to pneumocystis carinii infections and autoimmune diseases, mainly directed against blood cells hemolytic anemia, thrombocytopenia, and neutropenia. Xlinked hyper igm syndrome genetics home reference nih. The putative genetic lesion is in the aicda gene found at 12p. Hyper igm syndromes are a group of rare disorders in which the immune system. The term hyper igm syndrome identifies a heterogeneous group of genetically inherited disorders that are characterized by susceptibility to opportunistic infections and decreased serum levels of igg and iga, but normal or elevated igm. However, it is important to note that patients may also have normal levels of all immunoglobulins early in life. Hyperigm syndrome definition hyperigm syndrome is a primary immunodeficiency disorder in which the childs body fails to produce certain specific types of antibodies.
Hyperigd syndrome is a rare autosomal recessive disorder in which recurring attacks of chills and fever begin during the first year of life. Causes of hyperigm syndrome including triggers, hidden medical causes of hyperigm syndrome, risk factors, and what causes hyperigm syndrome. As a result, people are more susceptible to bacterial infections. Autosomal dominant hyper ige syndrome adhies is a primary immune deficiency characterized by the classic triad of recurrent skin boils, cystforming pneumonias, and extreme elevations of serum ige. Hyper igm syndromes nord national organization for rare. A number of different genetic defects can cause the hyper igm syndrome. The most common and the most clinically severe of these is an xlinked deficiency in cd40 ligand cd40 l.
One would expect opportunistic infections in any immunodeficiency syndrome. Doctors and medical specialists for hyperigm syndrome. Nemo deficiency syndrome immune deficiency foundation. Hyper igm syndrome is a collective name for a heterogeneous group of disorders united by defects in antibody isotype class switching and somatic hypermutation. The most common symptoms are skin disease and susceptibility to certain bacterial infections that can be severe and affect. It is the most common form of hyper igm syndrome, accounting for approximately 70% of cases. They can be classified as defects of signalling through cd40 causing both a. The hyper igm syndromes are a group of rare inherited immune deficiency disorders. Autosomal dominant hies has been shown to be mainly due to stat3 mutations. However, because these symptoms, such as a high fever, are typical in early childhood, many doctors and parents may not recognize the symptoms as being abnormal until the child is older. Despite the name, high levels of igm are inconsistently found in all forms of hyperigm syndrome. In this type, immature b cells cannot receive signal 2 from helper t cells which is necessary to mature into mature b cells. 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%. It causes immunodeficiency and susceptibility to infections.
For a discussion of genetic heterogeneity of immunodeficiency with hyper igm, see higm1 308230. Mutations of cd40, the receptor for cd40l, cause a rare autosomal form of. Due to the progress in understanding of this condition, achieved in the recent. Since the autosomal recessive forms of higm require that the gene on both chromosomes be affected they are less common than the xlinked conditions. 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. 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. The hyper igm syndrome higm is one of the rarest primary immunodeficiencies. Hyperigm syndrome definition of hyperigm syndrome by. 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.
People with this disorder have abnormal levels of proteins called antibodies or immunoglobulins. Diagnosis of hyper igm syndrome is suspected based on clinical criteria, including recurrent sinopulmonary infections, chronic diarrhea, and lymphoid hyperplasia. Recently, one lesion on the left knee had become slightly red. Unlike other hyper igm syndromes, the type 2 patients identified thus far did not present with a history of opportunistic infections. Xlinked immunodeficiency with hyperimmunoglobulin 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. Our mission is to improve the treatment, quality of life and the long term outlook for children and adults living with hyper igm through research, support, education, and advocacy to families and patients. Hyper igm syndrome is caused by genetic mutations of genes involved in immune response and affects a very small part of population. Hyperigm syndrome type 4 which is a defect in class switch recombination downstream of the aicda gene that does not impair somatic hypermutation. Aug 30, 2017 idf 2017 national conference session, hyper igm syndrome higm was presented by caroline kou, md on june 16, 2017. Children with hyperigm syndrome have frequent sinus and lung infections. Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. Diagnosis of hyperigm syndrome is suspected based on clinical criteria, including recurrent sinopulmonary infections, chronic diarrhea, and lymphoid hyperplasia.
Antigenspecific responses are usually decreased or absent. Immunodeficiency with hyper igm type 1 genetic and rare. As a result, patients have decreased levels of igg and iga and normal or elevated levels of igm. May 31, 2007 xlinked hyper igm syndrome higm1, a disorder of abnormal t and bcell function, is characterized by low serum concentrations of igg, iga, and ige with normal or elevated serum concentrations of igm. Symptoms of higm syndrome usually appear within the first 2 years of life and may include1,2. 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. Autosomal dominant hyperige syndrome genetics home. Hyper igm syndrome type 2 is estimated to affect fewer than 1 in 1,000,000 people in the general population. Hyper igm syndrome type 4 which is a defect in class switch recombination downstream of the aicda gene that does not impair somatic hypermutation.
Autosomal dominant hyperige syndrome caused by stat3 defects, called job syndrome, have characteristic facial, dental, and skeletal abnormalities. Autosomal dominant hyperige syndrome adhies, formerly known as job syndrome, is a condition that affects several body systems, particularly the immune system. What is xlinked hyperigm syndrome xlinked hyperigm syndrome omim 308230 is a genetic immunodeficiency syndrome that presents with bacterial and opportunistic infections from an early age. The characteristic facial features are usually set by age 16. Hyper igm syndrome can be caused by at least four different molecular genetic defects, 16 the most common of which affects the gene on the x chromosome encoding cd40 ligand, a tcell surface molecule responsible for instructing b cells to switch from igm to igg, iga, and ige production. What are the clinical characteristics of hyper ige syndrome. Hyper igm syndrome an overview sciencedirect topics. To research the causes of hyperigm syndrome, consider researching the causes of these these diseases. Autosomal dominant hyperige recurrent infection syndrome1 hies1. The nemo deficiency syndrome is a complex disease caused by genetic mutations in the xlinked nemo gene also known as ikk gamma or ikkg. Hyperigm syndrome is characterized by normal or high levels of immunoglobulin m igm and decreased levels or absence of other immunoglobulins.
The diagnosis of xlinked hyper igm syndrome is established in a male. Hyperigm syndrome is a collective name for a heterogeneous group of disorders united by defects in antibody isotype class switching and somatic hypermutation. For the other 3 mutations, they run in an autosomal recessive manner, this is, the chances to have the condition is 25%, increasing if the parents are. 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. Hyper igd syndrome is the less severe form of a metabolic disorder known as. Patient presentation an 18monthold female came to clinic with a history of bumps on her legs for 5 weeks. An update on the hyperige syndromes arthritis research.
Hyper igd syndrome is a rare autosomal recessive disorder in which recurring attacks of chills and fever begin during the first year of life. The hyperigm syndrome higm is one of the rarest primary immunodeficiencies. 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. Jun 25, 20 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. Symptoms are usually present before the age of one. The most common form of hyper igm is xlinked hyper igm, which primarily affects boys, except in rare cases. See also overview of immunodeficiency disorders and approach to the. Because isotype switching of antibody cannot occur, there is a selective hypogammaglobulinemia of igg, iga, and ige. Affected individuals can fall anywhere along this spectrum and it is important to remember every person is unique and the disorder may affect them differently from how it affects another person. Proliferation of igm producing plasma cells may lead to. Hyper igm syndrome is a very rare, oneinamillion, and potentially lifethreatening genetic mutation that severely compromises the immune system.
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