What is Hyper-IgE Recurrent Infection Syndrome?
Hyper-IgE Recurrent Infection, formerly called Job syndrome, is a rare disorder that primarily impacts the immune system, leading to frequent infections. While the disease can affect multiple systems and parts of the body, it commonly causes inflammation and pneumonia. These recurring infections can further compromise other bodily systems, resulting in additional health complications.
To date it is believed to occur in less than 1 million people globally, making it very rare.
This syndrome is also known as:
Buckley syndrome; HIES; Autosomal Dominant Hyper IgE syndrome; Hyper-ige Syndrome, Autosomal Dominant; Job Syndrome
What gene change causes Hyper-IgE Recurrent Infection syndrome?
Changes in the STAT3 gene are responsible for most of the cases of this syndrome. It is inherited in an autosomal dominant pattern.
In the case of autosomal dominant inheritance, just one parent is the carrier of the gene mutation, and they have a 50% chance of passing it onto each of their children. Syndromes inherited in an autosomal dominant inheritance are caused by just one copy of the gene mutation.
The following genes IL6R, IL6ST, DOCK8 and ZNF341 are linked to autosomal recessive variants of the syndrome.
Autosomal recessive inheritance means an affected individual receives one copy of a mutated gene from each of their parents, giving them two copies of a mutated gene. Parents, who carry only one copy of the gene mutation will not generally show any symptoms but have a 25% chance of passing the copies of the gene mutations onto each of their children.
What are the main symptoms of Hyper-IgE Recurrent Infection syndrome?
The main symptoms are frequent infections, including pneumonia and inflammation. Recurrent pneumonia can also cause air-filled cysts to develop in the lungs. While constant and repeating inflammation can cause damage to body tissue. Recurrent skin infections are also triggered by the syndrome, and specifically eczema.
Skeletal abnormalities are also a common feature of this syndrome, including scoliosis, a reduction in bone density also features, and individuals may be more susceptible to bone fractures. Individuals may also experience symptoms that affect their teeth, particularly the failure of the baby or first teeth to fall out when they should.
Other possible symptoms include heart abnormalities, brain abnormalities (that do not impact intellectual and cognitive ability and or functioning), and unique facial features.
Possible clinical traits/features:
Lymphoma, Joint hypermobility, Abnormal eosinophil morphology, Osteopenia, Hypertelorism, High palate, Increased circulating IgE level, Gingivitis, Wide nose, Cellulitis, Atelectasis, Abnormality of the nose, Abnormal fingernail morphology, Abnormality of temperature regulation, Dilatation, Abnormal blistering of the skin, Coarse facial features, Cleft palate, Delayed eruption of teeth, Eczematoid dermatitis, Eosinophilia, Deeply set eye, Craniosynostosis, Otitis media, Persistence of primary teeth, Paronychia, Osteomyelitis, Autosomal dominant inheritance, Skin rash, Pruritus, Frontal bossing, Prominent forehead, Recurrent fungal infections, Scoliosis, Recurrent Staphylococcus aureus infections, Recurrent fractures, Recurrent sinopulmonary infections, Reduced bone mineral density, Skin ulcer.
How is it diagnosed?
To find out if someone has a diagnosis of Hyper-IgE Recurrent infection syndrome, it is important to have a consultation and evaluation with a clinical genetic specialist. Specialists may also suggest specific genetic testing or other types of tests to help reach a diagnosis. FDNA’s AI technology can help speed up the diagnostic process by analyzing facial features and other health information.
