Monogenic etiologies of atopic dermatitis: A comprehensive systematic review of 1165 patients

Summary: Abstract Body: Atopic dermatitis (AD) is the most common skin disease in children that affects 10-20% of the general pediatric population and about 10% of adults. It is characterized by inflammation and itching, and is often associated with a history of atopy in patients or their families. AD is a complex disease with mainly multifactorial etiology. However, a small subset of patients has unifactorial etiology caused by a mutation in a single gene that is highly penetrant and afflicts any 1% of the normal population. Recently, the widespread use of genome/exome sequencing made it possible to determine this high-risk Mendelian subset from a larger group of patients with multifactorial etiology. Despite several reported cases of monogenic AD, it is not clear how useful genetic testing is in a clinical setting, and genetic testing is rarely incorporated into clinical assessments. To find out how useful genetic testing is and to encourage broader molecular testing, we conducted a systematic literature review to identify the genotypic and phenotypic spectra associated with monogenic AD. The inclusion criteria were met by 449 of 31,031 articles. In 1165 patients 170 AD-associated genes were identified, including 53, 31, and 82 genes with strong, moderate, and weak evidence for causality, respectively. Autosomal recessive inheritance predominated (57%). AD onset age was 10.18±10.62 months, with an interquartile range of 2 to 12 months. The FLG, DOCK8, CARD11, STAT3, EDA, SERPINB7, SPINK5, and WAS are the most frequently reported AD-associated genes with strong causality. 76 (44.7%) out of 170 belong to a catalog of inborn errors of immunity-related genes. AD has at least 170 monogenic etiologies and a genetic diagnosis is essential for effective management. Hassan Vahidnezhad¹, Amir Hozhabrpour², Zahra Nouri¹, Sajjad Biglari¹, Sara Minaeian², Fatemeh Vahidnezhad³, Johann E. Gudjonsson⁴, Hákon Hákonarson¹ 1. Children's Hospital of Philadelphia, Philadelphia, PA, USA, Philadelphia, PA, United States. 2. Iran University of Medical Sciences, Tehran, Tehran Province, Iran (the Islamic Republic of). 3. University of Maryland Eastern Shore, Princess Anne, MD, United States. 4. University of Michigan, Ann Arbor, MI, United States. Genetic Disease, Gene Regulation, Gene Therapy & Epigenetics