Background: G, male, was born at 39 GW by emergency CS from non-consanguineous parents. Prenatal US showed growth at lower limits of normal from 22 GW, short limbs and polyhydramnios. Amniocentesis karyotype was 46,XY. At birth weight and length were <3rd percentile, head circumference was between 10 and 25th percentile. At physical examination: short limbs, short neck, cryptorchidism, and microphallus. Early the baby presented mild respiratory distress and a severe episode of hypoglycemia corrected with infusion of D10% through umbelical vein catheter. In the next days he presented recurrent episodes of hypoglycemia treated with corticosteroids and feeding via NG tube and jaundice, that requested prolonged phototherapy. Furthermore he was recalled at hypothyroidism screening.
Objective and hypotheses: We speculate the hypotheses of congenital hypopituitarism.
Method: We investigated pituitary gland function and morphology and excluded multiorgan involvement. We initiate also genetic evaluation.
Results: US and radiological findings were negative for CNS, abdominal, cardiothoracic, and skeletal abnormalities. Laboratory confirmed lack of all pituitary hormones but no morphologic alterations of pituitary gland and stalk were shown by brain MRI. Considering hypotiroidism, hypogonadism, hypocorticism, and hyposomatotropism diagnosis of congenital multiple panhypopituitarism (CMPHD) was made. G was started on L-thyroxine, hydrocortisone and rhGH replacement therapy. At 3 months he was diagnosed with bilateral sensorineural hearing loss. Genetic evaluations excluded gene PROP1 mutations (cause of CMPHD2) but showed a missense variant (p.Leu196Pro, CTG>GGG) in exon four of LHX3 gene not yet described responsible for CPHD3. Functional studies demonstrated that this variation determines the inability of the synthesized protein to bind to DNA altering activity of the normal protein.
Conclusion: Because of the same mutation was detected in his mother, asymptomatic, the hypothesis that this mutation alone is the cause of baby G panhypopituitarism was discarded. SNPs array excluded hemizygosity so we speculated that his phenotype may be correlated with a digenic form.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology