Morbid Constellation of Osseous and Vascular Abnormalities in a Female Patient with Congenital Central Hypoventilation/Overgrowth Syndrome

Background: Congenital Central Hypoventilation Syndrome (CCHS), is a condition characterized by ventilatory impairment that results in arterial hypoxemia. Studies revealed that the vast majority of patients with CCHS are free from any associated pulmonary, cardiac or brainstem pathologies. Material and Methods: F.R is a 20 -year-old- Austrian-girl presented in my consultation seeking advice for her unpleasant clinical history. In her early life, seizures were the first serious clinical presentation. Followed later on with hypertension, bouts of respiratory dysfunction and impairment of consciousness. In 2019 she underwent surgical intervention to remove a 2 cm hamartoma (posterior upper aspect of the right thigh). Few years later, another hamartoma on the ventral side of the tongue has been identified as well. Early on, she received the diagnosis of Mediterranean fever syndrome and the geneticist encountered homozygosity to the MEFV M694V mutation as the reason behind the constellation of the current unpleasant symptomatology. Later on a presumptive diagnosis of Ehlers-Danlos syndrome-hypermobile type has been suggested in other Medical Institutions. We proceeded with our documentation via clinical and radiological phenotypic characterizations. Results: Clinical examination showed growth above the 97th percentile (overgrowth) with no specific facial dysmorphic features. She manifested generalized ligamentous hyper laxity. Her ligamentous hyperlaxity was compatible with 6 points out of 9 in correlation with Beighton scoring test. On the bases of skeletal survey; lateral skull radiograph showed features of mastoid and temporal bone characterized with extensive-pneumatization. Axial CT scan shows bilateral hyper-pneumatization of the temporal bones, demonstrating expansion of aerial spaces with loss of the bony trabeculae and thinning of the mastoid bone. Mastoid cells appear to be in communication with a large intracranial epidural air cavity in the temporal and parietal regions. Reformatted CT scan of temporal bone, through coronal and axial images, at the level of the cavum tympani and the mastoid, showed a defect in the right tegmen appeared as cloudy/ opaque lesions around the cavum and the surrounding air cells. Contrast- enhanced computed CT angiography of the cervical and cerebral vasculature showed unusual malalignment and spiral twisting along several vascular segments resulted in the mal-development of basilar artery stenosis without atherosclerosis. The current patient manifested overgrowth syndromic entity with a constellation of osseous and vascular abnormalities resulted in a clinical course of congenital central hypoventilation syndrome. Conclusion: The etiology behind the extension of pneumatization has most likely occurred because of defective ossification of the occipito-mastoid synchondrosis . The reason behind the extension of pneumatization into the occipital and parietal bone is probably due to incomplete closure of the occipito-mastoid synchondrosis, lambdoid and sagittal sutures, which usually close in early adulthood and later, even at the age of thirties. In our patient, we postulate that the history of multiple hamartomas and abnormal vascular phenotype in conjunction with extensive hyper-pneumatization of the skull were the main etiology behind her unpleasant course of her devastating ailment regardless the genetic results. Our impression is neither Mediterranean fever syndrome nor Ehlers-Danlos syndrome seem compatible with her current constellation of osseous and vascular abnormalities. The overall clinical and imaging findings are highly likely in connection with either one of the different types of overgrowth syndromes or might be a novel syndromic association. We believe that congenital central hypoventilation is a symptom complex rather than a diagnostic entity.