Lethal junctional epidermolysis bullosa with pyloric atresia due to compound heterozygosity for two novel mutations in the integrin β4 gene.

[junctional epidermolysis bullosa]

Junctional epidermolysis bullosa with pyloric atresia (JEB-PA ) is a rare autosomal recessive disease with blister formation within the lamina lucida due to mutations in the integrin β 4 (ITGB 4 ) and α 6 (ITGA 6 ) genes .A female preterm infant , first child of healthy non-consanguineous parents , was born at 26 + 4 weeks of gestation by caesarean section , following polyhydramnion and abruption of placenta . She presented with extensive areas of denuded skin on both lateral sides of the head , neck and extremities . Auricles were hypoplastic . Abdominal ultrasound and X-ray were suggestive of pyloric atresia which was revised surgically on the 4 th day of life . Further course was complicated by progressive skin detachment , sepsis , and renal insufficiency with fatal outcome at 18 days of age . Immunofluorescence mapping of cryopreserved skin showed junctional cleft formation with negative staining for integrin α 6 and integrin β 4 . Mutational analysis disclosed compound heterozygosity for two novel nonsense mutations in the ITGB 4 gene : c .600 dupC /p .F 2 01 fsX 14 and c .2533 C >T /p .Q 845 X . 2 subsequent pregnancies were terminated following prenatal diagnosis disclosing the same ITGB 4 mutations , a 4 th pregnancy was unaffected .We describe a case of lethal JEB-PA with negative immunoreactivity to integrin α 6 and integrin β 4 predicting a poor outcome . Identification of compound heterozygosity for two novel ITGB 4 mutations in the affected preterm infant permitted prenatal diagnosis and finally birth of a healthy sibling .

Diseases
Validation

Diseases presenting "sepsis" symptom

acute rheumatic fever

carcinoma of the gallbladder

congenital diaphragmatic hernia

cushing syndrome

cystinuria

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

focal myositis

harlequin ichthyosis

heparin-induced thrombocytopenia

hirschsprung disease

homocystinuria without methylmalonic aciduria

inclusion body myositis

junctional epidermolysis bullosa

kindler syndrome

lamellar ichthyosis

locked-in syndrome

malignant atrophic papulosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

monosomy 21

primary effusion lymphoma

primary hyperoxaluria type 1

pyomyositis

scrub typhus

systemic capillary leak syndrome

typhoid

This symptom has already been validated