Complex Vascular Anomalies : NEET SS Pediatrics

What is Complex Vascular Anomalies?

They represent abnormal or excessive growth of venous structures. Venous Malformations are considered overall MC vascular malformations, with an incidence of 1 in 5000 to 1 in 10000. Mostly arises from Somatic variants in PIK3CA and TIE2/TEK genes- involved in PI3K/AKT/mTOR pathway. Slow flow predisposes to pain, swelling & thrombosis in many patients.

Important examples

Blue Rubber Bleb Nevus syndrome (BRBNS)

• The most common gene: is TIE 2 or TEK
• Inheritance: Sporadic or AD
• Key features: Multiple venous malformations(VMs)
• Skin: Blue-purple rubbery lesions
• Liver manifestations
• Intestine: GIT bleeding leading to the rise of iron deficiency anemia.
• It can involve any part of the intestine from mouth to anus, large and small intestine in particular, and rarely involves the sides and bottom of the tongue.

Treatment

Sirolimus, Anemia management, In severe intestinal cases, palliation by intestinal resection can be done.

Glomangioma (Glomuvenous malformation)

• MC gene: GLMN
• Inheritance: AD
• Key features: Multiple superficial subcutaneous lesions that are bluish-purple in color with non-rubbery, soft-to-firm consistency. The same appearance can be seen in all family members.
• Treatment: Laser or sclerotherapy/surgery.

Capillary Malformations (CMS)

Also called Port Wine Stains. Present since birth, CMs comprise mature dilated dermal capillaries, producing macular circumscribed, pink to purple lesions. MC Site: Head Neck, 90% are unilateral. It can occur as an isolated form or as a part of some syndrome. As age increases, these become darker & pebbly in consistency. Some may become popular & bleed. D/D: Nevus Simplex (Transient, Midline Lesions). Unilateral CMS associated with: Sturge Weber Syndrome(SWS), Klippel-Trenaunay Syndrome

Treatment

• Best-Pulsed Dye Laser
• It is initiated as early as possible, preferably in infancy.
• Some reappear later
• Camouflaging Cosmetics also play a role.

Nelson Table- Syndromes Associated With CM

• Sturge-Weber Syndrome
• Klippel- Trenaunay Syndrome
• Parkes-Weber Syndrome
• Macrocephaly-CM Syndrome
• CM-AVM Syndrome
• VHL Disease
• Rubinstein- Taybi Syndrome
• Roberts Syndrome
• Coat Disease
• Phakomatosis Pigmentovascularis
• Diffuse CM with Overgrowth
• Bannayan-Riley-Ruvalcaba Syndrome

Syndromic Vascularis Anomalies

PIK3CA-Related Overgrowth Spectrum (PROS) Disorders. Comprise a group of disorders due to somatic mosaic mutations in the PI3K/AKT/mTOR Pathway.

Clinical Diagnostic Criteria- Required Criteria

PIK3CA pathogenic variants

• Congenital or early childhood onset
• Sporadic, without family history & mosaic distribution
• Affected patients have findings from category A or B
  • Category A (>2 Features)
    • Adipose, muscle, nerve & skeletal overgrowth
    • Capillary, venous, AV, or LM
    • Epidermal nevus
  • Category B (Isolated Features)
    • Large, isolated LM
    • Isolated macrodactyly, hands, feet, or limbs overgrowth
    • Truncal adipose overgrowth
    • Hemi or B/L Dysplastic Megalencephaly
    • Epidermal nevus
    • Seborrheic Keratosis

Syndromes Included

• Klippel- Trenaunay Syndrome
• Macrocephaly-CM Syndrome
• Large head: developmental delay, hydrocephaly
  • Reticular Cms
  • Overgrowth of one or more limbs
• CLOVES syndrome:
  • CLO - Congenital lipomatous overgrowth
  • V - Vascular malformations (CM, LM, VM, AVM+/-)
  • E - Epidermal nevus
  • S - Skeletal/spinal/scoliosis
  • Increased risk of Wilms tumor risk
• CLAPO Syndrome:
  • C - CM on lower lips
  • L - LM on face and neck
  • A - Asymmetry
  • P - Partial
  • O - Overgrowth.

Also Read: Surfactant Dysfunction Disorders

Klippel-Trenaunay Syndrome

This term historically denotes a combination of Complex mixed, slow-flow vascular malformations (CMS, VMs, LMs) with overgrowth of bony and soft tissues.

• CMs comprise the most common vascular lesions.
• They are usually congenital, U/L lower limb being more commonly involved.
• The deep venous system is absent or hypoplastic.
• The remaining venous system may also be anomalous
• Venous blebs or vesicular lymphatic lesions may present on the surface
• Complications: Pain, Infection, Thrombophlebitis, hematuria, bleeding PR
• Investigations: Colour Doppler, MRI

Treatment

• Medical: Sirolimus, Anticoagulation
• Surgery: Sclerotherapy or endovenous laser ablation (if venous malformations are present)
• Supportive:
  • Compression Bandages
  • Orthotic Devices: Spine involvement
  • Ortho Surgery for limb - length Discrepancies

RASopathies

• Parkes Weber Syndrome = PKWS
• Features Include
  • Multiple Microscopic AV Fistulae
  • Capillary Malformations
  • Soft tissue & bat overgrowth
  • It is difficult to treat.

Kasabach-Meritt Phenomenon (KMP)

A life-threatening Complication of Kaposiform Hemangioendothelioma (KHE)- A rare vascular tumor of infancy, presenting as red to purple firm plaques on the lateral neck, axilla, trunk, or extremities. KMP Manifests in infancy & comprises, Rapidly enlarging KHE, Thrombocytopenia, Consumption Coagulopathy, Microangiopathic Hemolytic Anemia

It can be seen in KHF, Tufted angiomas, and Congenital hepatic angiomas, but NEVER seen in Infantile Hemangiomas. Hypofibrinogenemia is also common.

Treatment

• Surgery for small lesions is often difficult
• Medical: Systemic Steroids + Vincristine
• Sirolimus is a 2nd line therapy
• High mortality despite the use of antiplatelet, antifibrinolytic agents, etc.

Hope you found this blog helpful for your NEET SS Genetic Disorders preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.