GeneDx, STAT3 Gene Sequencing

Collect at NMCP only Mon-Thursday by 1200

3123

Hyper-IgE syndromes

2-5 mL Blood - Lavender Top Tube

Ship overnight at ambient temperature, using a cool pack in hot weather. Specimens may be refrigerated for 7 days prior to shipping.

ambient

7-8 weeks

Hyper-IgE syndromes caused by mutations in the STAT3 and DOCK8 genes are characterized by eczema, sinopulmonary infections and greatly elevated serum IgE. Elevated IgE has also been observed in an individual with TYK2 deficiency and in individuals with Netherton syndrome, a disorder associated with mutations in the SPINK5 gene. STAT3 (Autosomal Dominant HIES): Patients with AD-HIES have lifelong eczema, eosinophilia, and recurrent staphylococcal skin abscesses (recalling the infliction of the biblical character Job). The abscesses are “cold”, i.e. with remarkably little inflammatory response. Serum IgE levels are characteristically at least 10-fold elevated. Patients are prone to cyst-forming pneumonia (typically staph, hemophilus or pneumococcus) and mucocutaneous candidiasis. The face may be coarse and asymmetric. Non-traumatic fractures and scoliosis are typical, and dental deciduation is delayed. Other features reported include hyperextensibility, coronary artery aneurysms, brain lesions, craniosynostosis, and Chiari malformations. Individuals with AD-HIES are also at an increased risk for malignancies, particularly lymphomas. DOCK8 Immunodeficiency Syndrome (DIDS): DIDS is similar to AD-HIES, but without the skeletal, dental and connective tissue findings. It can also be distinguished from AD-HIES by the increased number of cutaneous viral infections and the higher prevalence of severe allergies. In addition, although both AD-HIES and DIDS are associated with increased risk of sinopulmonary infections, AD-HIES infections are commonly due to S. aureus, while DIDS infections are more varied. Malignancies are more common with DIDS, with lymphomas and squamous cell carcinomas the most prevalent. TYK2 Deficiency: To our knowledge, only two patients have been reported with TYK2 mutations. Both patients had sinopulmonary infections, BCG infections and cutaneous viral infections; however, only one patient had elevated IgE and skin abscesses.6,7 Netherton Syndrome (NTS): Netherton syndrome (NTS) is a congenital disorder of the skin, hair and the immune system. NTS usually manifests at birth with generalized redness and scaling of the skin resembling non-bullous congenital ichthyosiform erythroderma (NCIE) or, rarely, with a collodion membrane. Generalized erythema and scaling may either persist lifelong, or develop into itchy, scaling plaques called “ichthyosis linearis circumflexa”. Associated are hair shaft abnormalities, in particular “bamboo hair” also known as “trichorrhexis invaginata”, which may lead to diffuse alopecia of the scalp and loss of eyebrows and eyelashes. Most patients have highly elevated serum levels of immunoglobulin E and various allergies. In severe cases, failure to thrive, growth retardation, and immune defects resulting in serious recurrent infections may complicate NTS.