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Am J Med Genet A. 2019 Jul;179(7):1346-1350. doi: 10.1002/ajmg.a.61169. Epub 2019 May 15.

Biallelic human ITCH variants causing a multisystem disease with dysmorphic features: A second report.

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Department of Clinical Genetics, North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Clinical Genetics Unit, Birmingham Women's & Children's Hospital NHS Foundation Trust, Birmingham, UK.
Department of Occupational & Environmental Medicine, Royal Brompton & Harefield NHS Foundation Trust, London, UK.
Department of Paediatric Respiratory Medicine, Royal Brompton & Harefield NHS Foundation Trust, London, UK.
Department of Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust & University College Hospital, London, UK.


We report a 23 year old female with biallelic truncating variants in the ITCH (Itchy E3 Ubiquitin protein ligase, mouse homolog of; OMIM60649) gene associated with marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. The condition has only been reported once previously (Lohr et al., American Journal of Human Genetics, 2010, 86, 447-453) in 10 children from an Old Order Amish family found to have a homozygous frameshift truncating variant in association with failure to thrive, chronic lung disease, motor and cognitive delay, and variable autoimmune diseases including autoimmune hepatitis, enteropathy, hypothyroidism, and diabetes. The condition is listed in OMIM as Autoimmune disease, Multisystem with Facial Dysmorphism (OMIM613385). The clinical course as well as the dysmorphic facial and limb features overlap closely with our patient. We believe the triad of marked syndromic short stature, chronic lung disease, and dysmorphism (with or without cognitive impairment and wider autoimmune involvement) is distinctive.


ITCH; asthma; camptodactyly; chronic lung disease; dysmorphism; short stature


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