RASA1-Related Parkes Weber Syndrome in a Neonate

Abstract

Parkes Weber syndrome is a rare congenital vascular anomaly, related to the RAS p21 protein activator 1 (RASA1) gene. It is characterized by capillary cutaneous malforma tions, bony and soft tissue hyperplasia, and multiple arteriovenous fistulas throughout the affected upper or lower extremity. These arteriovenous fistulas can be associated with lifethreatening complications such as bleeding, thrombosis, and high output heart failure. In this report, we present a neonate who had a disproportionately hypertrophied left upper limb with portwine stain, dystrophy of the left humerus, and hypertrophy of the left clavicle on Xray, and arteriovenous malformation and massive dilatation of the left subclavian artery on magnetic resonance angiography. Exome sequencing analysis revealed a novel heterozygous splicing mutation (c.1776+2T>A) in the RASA1 gene. To the best of our knowledge, this report is the first case of RASA1related Parkes Weber syndrome in Korea.

A giant arteriovenous malformation and fistula in a newborn with Parkes Weber syndrome. Case report

“…According to the classification published by the International Society for the Study of Vascular Anomalies, PWS is defined as combined capillary malformation (CM), fast flow arteriovenous malformations (AVM) and arteriovenous fistulas (AVF) associated with limb overgrowth [1,3]. Warm, pink to red macular skin lesions known as a port-wine stain or pseudo capillary malformation can also be seen on the affected limb [3,9]. Other common signs include lymphoedema and lymphatic vesicles that can be seen on the skin.…”

“…As a result of tissue hypoxia, due to the steel phenomenon created by the AVFs and release of angiogenic growth factors, neovascularization of the cartilaginous growth centers is increased. AVFs can occur anywhere in the body including cutaneous, subcutaneous, intramuscular, intraosseous, and cerebral regions [3,13].…”

“…PWS is frequently misdiagnosed as Klippel-Trenaunay syndrome (KTS), which is characterized as a triad of capillary, venous and lymphatic malformations associated with limb overgrowth, but without arteriovenous fistulas, as it is in PWS [3]. That is why cardiac failure due to volume overload is not typical in KTS patients as opposed to PWS patients.…”

“…Radiation exposure is, of course, a concern in paediatric imaging, but diagnostic quality remains the most important factor [14]. MRI angiography is also used to reveal musculoskeletal abnormalities and vascular malformations, such as engorged arteries, veins, capillaries and flow voids, as well as arteriovenous fistulas [3]. During cardiac MRI neonates need to be under general anesthesia and often require myorelaxants and induced apnoea.…”

“…According to the classification by the International Society for the Study of Vascular Anomalies, PWS is defined as a complex combined of fast-flow vascular malformation that includes arteriovenous fistulas, capillary malformations associated with limb overgrowth and RASA1 gene variations. [1] Capillary malformations are seen as warm, "geographic" pinkmacular skin lesion known as a port-wine stain on the affected limb [2,3]. PWS can affect both the upper and lower extremities, however, it commonly affects one of the lower limbs.…”