A210 NEONATAL INFLAMMATORY SKIN AND BOWEL DISEASE CAUSED BY A HOMOZYGOUS EGFR MUTATION: A CASE REPORT AND REVIEW OF THE MEDICAL LITERATURE.

Epidermal growth factor receptor (EGFR) and its ligands are cell signaling molecules involved in diverse cellular functions, including cell proliferation, differentiation, motility, and cell survival. EGFR overexpression or over activity has been frequently described in association with a number of malignancies, most commonly lung carcinoma; however inherited loss of function mutations in the EGFR gene are extremely rare. To describe a 5-year old child with a complex medical history in whom a homozygous mutation in the EGFR gene was identified. Case report and literature review A now 5 year-old girl, born to non-consanguineous parents, was delivered following preterm labor at 27 weeks gestation. She weighed 890g. The pregnancy was complicated by polyhydramnios. Shortly after birth she was noted to have fragile skin with widespread erythema along with papules and pustules over her trunk and extremities. Clinical features included the following: downslanting palpebral fissures, thick eyebrows, no scalp hair, arachnodactyly, large feet with cavus and short sternum. She had a large ventriculoseptal defect and mitral valve regurgitation. Skin biopsy at 3 months of age found no histomorphologic alterations. There were no features of any inflammatory process. Testing for an interleukin 1 receptor antagonist deficiency was negative. Her skin has been persistently problematic with frequent Staphylococcal infections. Her scalp hair is sparse and coarse. She subsequently developed Fanconi syndrome and polycystic kidney disease. She has had frequent hospital admissions with skin and GI infections, including recurrent Clostridium difficile. She has had failure to thrive and chronic watery diarrhea since the age of 4 years. Upper endoscopy and colonoscopy revealed an antral gastritis and mild, non-specific chronic inflammation on colonic biopsies. She has hepatomegaly and mild elevation of transaminases. Whole exome sequencing revealed that she is homozygous for Gly428Asp, a loss-of-function missense mutation in the EGFR gene. There have been only 3 reported cases of this mutation. Tow children were siblings from consanguineous parents of Roma descent. The third patient was also of Roma descent. All had similar characteristics to the patient presented here including sparse scalp hair, recurrent skin infections, failure to thrive, chronic diarrhea and nephromegaly. All were born prematurely and had IUGR. No patient survived beyond 2.5 years. To date, there is no known effective therapy for the condition. EGFR signaling abnormalities affect multiple organ systems and have a severe phenotype. We report the clinical presentation and oldest living.patient with this condition, highlighting the role for whole exome sequencing in patients where a diagnosis is elusive None

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