NeoQuest March 2025: Segmental Facial Patch in a Newborn

A term female infant is born via spontaneous vaginal delivery.  On initial physical examination, the infant has a sternal cleft.  Figure 1 notes the facial skin findings.  At 3 weeks of age, the patch has thickened and deepened in color.  A brain MRI reveals Dandy Walker malformation. 

Figure 1: Erythematous facial patch in the distribution of the V1 and V2 branches of the trigeminal nerve with demarcation at the midline.  Image from: Marshall C, Shah E, Siegel L, Riley M, Shmuylovich L, Mian A, Smyser S, Peglar Marsala L.  Unilateral facial lesion in an infant with known vermian hypoplasia. Neoreviews. (2025);26(3):e186–e190.¹

What additional finding is most likely associated with this constellation of features?

1. Coarctation of the aorta
2. Glaucoma
3. Leptomeningeal angioma
4. Lymphatic malformation

Answer: A. Coarctation of the aorta

Explanation:

The facial findings of the infant in the vignette are most consistent with a hemangioma because of its erythematous and blanchable appearance that became thicker and darker over time¹.  The additional findings of a sternal cleft and Dandy Walker malformation suggest that the infant has PHACES (posterior fossa malformations, hemangioma, arterial anomalies, coarctation of the aorta/cardiac defects, eye abnormalities, sternal malformations) syndrome.  Hemangiomas (as seen in both Figure 1 and Figure 2) and cardiac abnormalities are the most common manifestations of PHACES syndrome.^2,3,4 An infantile hemangioma is present in up to 98% of patients with PHACES syndrome.⁴  Therefore, an infantile hemangioma larger than 5 cm on the head, neck, upper arms, and upper trunk should lead to further evaluation with an ophthalmological examination, magnetic resonance imaging/magnetic resonance angiography (MRA) of the head, neck, heart, and aortic arch, and echocardiogram to evaluate for other associated findings.⁴ 

Figure 2: Various presentations of infantile hemangiomas in different children (A-C): (A) Red violaceous nodules on the forehead. (B) Pink-to-erythematous telangiectasias of the lower half of the face with ulceration of the lower lip. (C) Large segmental hemangioma of the left leg and perineum. Rapidly Involuting Congenital Hemangioma (RICH) (D-G): Longitudinal involution of a left posterior arm mass from 2 days to 1 year of age. Evolution of kaposiform hemangioendothelioma (G-H): (G) Starting as a subtle swelling of the chest wall, the lesion evolved into a (H) violaceous, edematous, ecchymotic mass over 2 weeks. Image from: Evans LL, Hill LRS, Kulungowski AM. Neonatal cutaneous vascular anomalies. Neoreviews. 2025;26(1):e12-e27.⁵

Infantile hemangiomas associated with PHACES syndrome may or may not be present at birth, appearing as a pale, mildly erythematous, or telangiectatic lesion that will evolve in its appearance over time.^1-3  Commonly located on the face, scalp, or cervical region, these hemangiomas are typically segmental, proliferate rapidly, and are extensive in size (greater than 5 cm).^1,2,4  They are typically treated with oral propranolol, a beta blocker, until the hemangioma has involuted.^3,4  There are several proposed mechanisms of action for the treatment of infantile hemangiomas with beta blockers, including vasoconstriction, induced apoptosis of infantile hemangioma capillary endothelial cells, and downregulation of the RAF-mitogen activated protein kinase cascade, which regulates vascular endothelial growth factor (VEGF) and fibroblast growth factor gene transcription.⁴ 

Coarctation of the aorta (Option A) is the most common cardiac finding reported with PHACES syndrome.²  The type of coarctation observed in infants with PHACES syndrome is often complex, associated with hypoplasia or interruption of the transverse aortic arch and/or the presence of dilation or an aneurysm in adjacent sections of the aortic arch.²  Additionally, the brachiocephalic vessels and aortic arch-sidedness are often abnormal.² 

The differential diagnosis for a segmental facial patch in a newborn includes Sturge-Weber syndrome (SWS) and Klippel-Trenaunay syndrome (KTS).  Capillary malformations are consistent with SWS and KTS, while infantile hemangiomas are associated with PHACES syndrome.⁵  Capillary malformations can be widespread, presenting as pink-to-red patches in the skin. In addition, they may be associated with bony and soft tissue overgrowth.⁵  In contrast, infantile hemangiomas present initially as a pale or faint macular lesion characterized by proliferation and involution.⁵  Superficial hemangiomas involving the epidermis and dermis progress into bright erythematous macules, papules, or plaques, while deep hemangiomas associated with subcutaneous tissue are characterized as blue, ecchymotic nodules underneath the skin surface.⁵  Capillary malformations commonly seen in SWS affect the ophthalmic division of the trigeminal nerve (V1) and are often associated with ipsilateral leptomeningeal angiomas (Option C) (Figure 3).⁶  

Figure 3: Port wine stain on forehead and alae of nose.  Image from: Nam GH, Merritt TA, Deming D, Clark RD, Gold J. Extensive capillary malformation and hemihypertrophy in a 37-week-gestation infant. Neoreviews. 2015;16(5):e326-e332.⁷

Eye anomalies appear rarely in PHACES syndrome, but when present, include microphthalmia, optic nerve hypoplasia, a funnel-shaped cavity in the optic disc (morning glory disc anomaly), and persistent fetal vasculature.²  In contrast, glaucoma(Option B) is frequently associated with SWS.^6,8 

KTS involves capillary malformations near the skin surface, bone malformations, soft-tissue overgrowth, and venous and lymphatic malformations (Option D) (Figure 4).^5,9  Lymphatic malformations vary in size and are often present in the extremities, sometimes extending into the pelvis. They can be a source of bleeding, pain, and infection.⁵  The capillary malformations in KTS typically affect the lower extremity limb, but they can also affect the upper limb or trunk.9  The capillary malformations place patients at risk for developing thrombophlebitis, deep venous thrombosis, and pulmonary embolism.⁵  KTS is not associated with cranial abnormalities that were found in the infant in the vignette.9 

Figure 4: Newborn with cutaneous hemangiomas found to have hepatic hemangioma associated with Klippel-Trenaunay syndrome. Image from: Fernández, KS. Solid tumors in the neonatal period. Neoreviews. 2014;15(2):e56-e68.¹⁰

Did you know?
Cervicofacial infantile hemangiomas located on the lower part of the face can affect feeding and breathing, especially when they involve the upper airway and subglottic area.  If stridor or a barky cough is present in an infant with a cervicofacial hemangioma, the infant should be promptly evaluated for a subglottic hemangioma causing airway obstruction.⁵ 

What genetic mutation is associated with the cutaneous capillary malformations in Sturge-Weber syndrome?
For a review of vascular malformations in neonates, refer to: Evans LL, Hill LRS, Kulungowski AM. Neonatal cutaneous vascular anomalies. Neoreviews. Jan 1 2025;26(1):e12-e27.⁵

NeoQuest March 2025 Authors:
Jeanette Van Steyn, MD, University of North Carolina, Chapel Hill, NC
Angelina June, MD, Fairfax Neonatal Associates, Fairfax, VA

References

1. Marshall C, Shah E, Siegel L, Riley M, Shmuylovich L, Mian A, Smyser S, Peglar Marsala L. Unilateral facial lesion in an infant with known vermian hypoplasia. Neoreviews (2025)26(3):e186–e190
2. Metry D, Heyer G, Hess C, et al. Consensus statement on diagnostic criteria for PHACE syndrome. Pediatrics. Nov 2009;124(5):1447-56
3. Rotter A, Samorano LP, Rivitti-Machado MC, Oliveira ZNP, Gontijo B. PHACE syndrome: clinical manifestations, diagnostic criteria, and management. An Bras Dermatol. Jun 2018;93(3):405-411
4. Winter PR, Itinteang T, Leadbitter P, Tan ST. PHACE syndrome--clinical features, aetiology and management. Acta Paediatr. Feb 2016;105(2):145-53
5. Evans LL, Hill LRS, Kulungowski AM. Neonatal cutaneous vascular anomalies. Neoreviews. Jan  2025;26(1):e12-e27
6. Sudarsanam A, Ardern-Holmes SL. Sturge-Weber syndrome: from the past to the present. Eur J Paediatr Neurol. May 2014;18(3):257-66
7. Grace H. Nam TAM, Douglas Deming, Robin D. Clark, June-Anne Gold. Extensive capillary malformation and hemihypertrophy in a 37-week-gestation infant. Neoreviews. 2015;16(5):e326–e332
8. Mantelli F, Bruscolini A, La Cava M, Abdolrahimzadeh S, Lambiase A. Ocular manifestations of Sturge-Weber syndrome: pathogenesis, diagnosis, and management. Clin Ophthalmol. 2016;10:871-8
9. Vahidnezhad H, Youssefian L, Uitto J. Klippel-Trenaunay syndrome belongs to the PIK3CA-related overgrowth spectrum (PROS). Exp Dermatol. Jan 2016;25(1):17-9
10. Fernández KS. Solid tumors in the neonatal period. Neoreviews. 2014;15(2):e56–e68