Postnatal neonatological intensive care, diagnostics, therapy and diagnosis of PROS
A female infant was delivered weighing 3,450 g (74thpercentile), 49 cm length (27th percentile) and 35 cm head circumference (71th percentile) by cesarean section with neonatological standby of an ex-utero intrapartum treatment (EXIT) procedure in 39th week of gestation (Fig. 2 a, b). The newborn adapted well and presented in good condition: APGAR 8/9/10, arterial umbilical cord pH 7.39. Initially, it required no active management and was immediately transferred to the neonatologist care unit. During inpatient stay, the infant underwent an extensive interdisciplinary neonatological intensive care with regular ultrasound and MRI follow-up (Fig. 2 c, d). The lymphangioma seemed to be stable. With intention of tumor regression as well as obtaining tissue, several sonographically controlled biopsies of the neck with multiple injections of Picibanil (OK-432) and the partial resection of areas of the tumor were performed. Attempting tumor size restriction with Propranolol, based on the histopathological suspicion of a hemangioma and the meanwhile significant tumor progression, failed. The histopathological findings and the clinical presentation of the tumor rather suggested a lymphangioma. In the meantime, an evaluation by ultrasound and MRIs of the neck showed a semicircular tumor extension, reaching cranially to the mastoid and intrathoracally to the carina with increasing infiltration of the base of the tongue and marked constriction of the cervical vessels without airway obstruction. With histopathological evidence of markers of the mTOR pathway, associated with a number of overgrowth disorders, a therapeutic approach with Sirolimus was initiated and resulted in a minimal size reduction. Nearly during the entire inpatient stay and despite an extensive interdisciplinary management, the etiology of the lympangioma remained unclear and the conventional molecular genetic investigation a challenging process. To establish a final diagnosis next generation sequencing (NGS) was performed and subsequently resulted in the detection of the missense mutation c.1633G>A;p.Glu545Lys.