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CASE REPORT
Year : 2019  |  Volume : 12  |  Issue : 6  |  Page : 524-528  

PHACES syndrome – A rare case report


Department of Ophthalmology, JNU Medical College and Research Institute, Jaipur, Rajasthan, India

Date of Submission29-Oct-2018
Date of Acceptance29-Mar-2019
Date of Web Publication17-Oct-2019

Correspondence Address:
Sujit Das
Department of Ophthalmology, JNU Medical College and Research Institute, Jaipur - 302 017, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_151_18

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  Abstract 


PHACES syndrome stands for posterior fossa malformations–hemangioma–arterial anomalies–cardiac defects–eye abnormalities–sternal cleft all together known as “PHACES syndrome.” It is a rare cutaneous condition characterized by multiple congenital abnormalities. It affects girls nine times more often than boys. A 3-year-old girl presented with hemangioma of the face, palate, lips, and eyelids and developmental delay associated with seizure episodes. In the ocular examination, congenital cataract, choroidal coloboma, and optic disc hypoplasia were seen. Systemically, there were sternal cleft, ventricular septal defect, and posterior fossa arachnoid cyst and central nervous system vascular abnormalities. Diagnosis was made from systemic examination and ocular examination along with imaging study of the head and chest. PHACES syndrome needs to be managed by a multidisciplinary team of experts such as cardiologist, ophthalmologist, neurologist, and neurosurgeon. Every child with PHACES syndrome should be evaluated for glaucoma and associated pituitary function at each visit.

Keywords: Hemangioma in children, PHACES syndrome, vascular anomaly in children


How to cite this article:
Das S. PHACES syndrome – A rare case report. Med J DY Patil Vidyapeeth 2019;12:524-8

How to cite this URL:
Das S. PHACES syndrome – A rare case report. Med J DY Patil Vidyapeeth [serial online] 2019 [cited 2019 Nov 19];12:524-8. Available from: http://www.mjdrdypv.org/text.asp?2019/12/6/524/269416




  Introduction Top


PHACES syndrome is the association between large infantile hemangioma, usually of the face, and birth defects of the brain, heart, eyes, skin, and arteries. The association of anomalies and the PHACES acronym was first coined by Dr. Vali Reese and Dr. Ilona Frieden as a cutaneous condition characterized by is a cutaneous condition characterized by posterior fossa malformations–hemangioma–arterial anomalies–cardiac defects–eye abnormalities–sternal cleft and supraumbilical raphe.[1] PHACES syndrome is rare and affects girls nine times more often than boys. Hemangiomas associated with PHACES syndrome are usually small or not visible at birth but are easier to see during the during the upcoming weeks. Hemangioma linked with PHACES syndrome tends to cover a large area of the face, head, or neck, either as one lesion or as many single lesions.[2] The main concern of PHACES syndrome is its association with complications – seizure disorder, loss of sight, hearing defect, bleeding from ulceration, and cardiac complications. PHACE (S) syndrome is a clinical diagnosis, and there is no known cause of it.[3] The relationship of abnormalities found in PHACE syndrome suggests that it is a problem in embryonic development at a specific critical time, probably between 3 and 12 weeks of gestation when blood vessels are developing.[3]


  Case Report Top


A 3-year-old girl presented to our eye outpatient department with visual difficulty, watering, and hemangioma of the eyelids. Hemangioma was present since birth. She had a developmental delay with mild gait abnormality. She had a history of several episodes of seizure attacks for which she was on phenytoin (5 mg/kg daily). There was no history of any bleeding from hemangioma sites. On examination, she had intense photophobia, and visual assessment could not be done. Apart from her eyelids and conjunctival capillary hemangioma [Figure 1], there was a right-sided facial segmental hemangioma of >5 cm [Figure 2]. Hemangioma also involved the lower lip [Figure 3] and the palate [Figure 4]. Considering the possibility of PHACES syndrome and its association with glaucoma, she was examined under general anesthesia. Her intraocular pressure was 14 mmHg in both the eyes, and corneal diameter was 10.7 mm vertically and 11.6 mm horizontally, which were normal. There was congenital cataract [Figure 5], and fundus examination showed choroidal coloboma [Figure 6] with optic disc hypoplasia in the right eye. The left eye was found normal. Refraction under atropine ointment showed 0.25 DC *90° in the right eye and 0.25 DS in the left eye. She was then referred to a pediatrician for further evaluation. On systemic examination, her height was 8.5 cm and weight was 10 kg and she had a parasternal systolic murmur with sternal depression [Figure 7]. A diagnosis of PHACES syndrome was made and advised for magnetic resonance imaging (MRI) brain, echocardiography, and chest X-ray. On two-dimensional echocardiography, there was presence of ventricular septal defect [Figure 8]. No coarctation of the aorta was present. MRI brain showed posterior fossa arachnoid cyst [Figure 9] measuring 2.9 cm × 2.1 cm × 1.5 cm at the right cerebellar area displacing the fourth ventricle with dilated tortuous vessels on MRI angiography [Figure 10]. Her chest X-ray was found normal [Figure 11]. Complete hemogram showed Hb – 10 gm%, erythrocyte sedimentation rate – 18 mm/h, sugar (F) – 112 mg/dl, urea – 26 mg/dl, and creatinine – 1 mg/dl, and routine urine microscopy was found normal. She underwent cataract surgery with lens implantation, but on follow-up, there was no visual improvement with refraction in the right eye. Oral propranolol (0.5 mg/kg/day) was started by a pediatric cardiologist to treat hemangioma and referred to a pediatric neurosurgeon for further management.
Figure 1: Eyelid and conjunctival hemangioma

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Figure 2: Facial hemangioma of >5 cm

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Figure 3: Lip capillary hemangioma

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Figure 4: Palate hemangioma

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Figure 5: Congenital nuclear cataract

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Figure 6: Choroidal coloboma

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Figure 7: Sternal cleft

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Figure 8: Ventricular septal defect

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Figure 9: Magnetic resonance imaging brain showing posterior fossa arachnoid cyst displacing the fourth ventricle

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Figure 10: Magnetic resonance imaging angiography of the brain

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Figure 11: Normal chest X-ray

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  Discussion Top


Posterior fossa anomalies (P), hemangioma (H), arterial anomalies (A), cardiac abnormalities and coarctation of the aorta (C), and eye abnormalities (E) all together are known as PHACE syndrome. Boulinguez et al. added the sternal cleft (S) to this acronym and changed the name to PHACES syndrome.[4] Most reported cases were sporadic, but mutations in the X-linked genes were proposed to cause this syndrome in some patients.[2] The diagnosis of the PHACES syndrome is based on the presence of a facial hemangioma with the area of >5 cm2 plus one major or two minor criteria.[5] Among ocular manifestations, the posterior segment abnormalities are included in the major criteria, and the anterior segment abnormalities are included in the minor criteria. Approximately one-third of the PHACES syndrome cases have eye involvements.[5] In a recent study on 23 cases of PHACES syndrome, 14% of the cases showed ocular involvement. Posterior segment abnormalities include morning glory disc anomaly, persistent fetal vasculature, peripapillary staphyloma, retinal vascular anomalies, optic nerve hypoplasia and atrophy, choroidal hemangioma, and chorioretinal coloboma.[5] Anterior segment abnormalities include cataract, microphthalmia, conjunctival hemangioma, posterior embryotoxon, corneal opacity, sclerocornea, iris coloboma, iris heterochromia, iris hypoplasia, and iris vessel hypertrophy. Other miscellaneous ocular abnormalities are congenital glaucoma, cryptophthalmos, proptosis, Horner syndrome, congenital third or fourth nerve palsies, strabismus, and ptosis.[5] Therefore, the presence of large facial hemangioma, along with posterior fossa arachnoid cyst, central nervous system vascular abnormalities, ventricular septal defect, cataract, conjunctival hemangioma, and chorioretinal coloboma in this patient confirmed the diagnosis of PHACES syndrome. Bleeding with ulceration, seizure disorder, and cardiac complications are the most common complication associated with PHACES syndrome.[6] In our patient, there were seizure episodes and cardiac problems. No bleeding history was present. In 1999, Coats et al. reported a case with PHACE syndrome and congenital glaucoma.[7] Unlike their report, in our case, the congenital glaucoma was not found. Propranolol, intralesional and oral steroid, interferon-α2a, aminocaproic acid, and partial resection[7] were used to treat facial hemangioma in the literature. Thus, the initiation of this drug (propranolol) in our patient was logical. Hypogonadotropic hypogonadism, secondary adrenal insufficiency, central hypothyroidism, and absolute growth hormone deficiency all are associated with PHACES syndrome.[8] One possible explanation for the acquired hypopituitarism is that the arachnoidal cyst located in the area of the sella may have caused chronic pressure on the adenohypophysis, leading to a progressive loss of function. As reported in the literature, intracranial cysts can cause a wide spectrum of endocrine insufficiencies.[9]


  Conclusion Top


Patients with large facial hemangioma must be evaluated for other manifestations of the PHACES syndrome, including eye diseases. In addition, the clinicians must be aware of the probable association between this syndrome and congenital glaucoma and perform the glaucoma workup for each patient with this syndrome. We also conclude that screening of pituitary functions in patients with PHACES syndrome and intracranial malformations is recommended both at diagnosis and during follow-ups. We suggest yearly follow-up with anthropometric measurements, clinical assessment of pubertal development, and laboratory evaluations of laboratory evaluation of thyroid function, adrenocorticotropic hormone and cortisol estimation and cortisol.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that name and initial will not be published and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Frieden IJ, Reese V, Cohen D. PHACE syndrome. The association of posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities. Arch Dermatol 1996;132:307-11.  Back to cited text no. 1
    
2.
Metry DW, Haggstrom AN, Drolet BA, Baselga E, Chamlin S, Garzon M, et al. A prospective study of PHACE syndrome in infantile hemangiomas: Demographic features, clinical findings, and complications. Am J Med Genet A 2006;140:975-86.  Back to cited text no. 2
    
3.
Watson P, Jacob D, Metry M. Patterns of infantile hemangiomas: New clues to hemangioma pathogenesis and embryonic facial development. Pediatr Neural 2006;11:696-8.  Back to cited text no. 3
    
4.
Metry DW, Dowd CF, Barkovich AJ, Frieden IJ. The many faces of PHACE syndrome. J Pediatr 2001;139:117-23.  Back to cited text no. 4
    
5.
Hartemink DA, Chiu YE, Drolet BA, Kerschner JE. PHACES syndrome: A review. Int J Pediatr Otorhinolaryngol 2009;73:181-7.  Back to cited text no. 5
    
6.
Bracken J, Robinson I, Snow A, Watson R, Irvine AD, Rea D, et al. PHACE syndrome: MRI of intracerebral vascular anomalies and clinical findings in a series of 12 patients. Pediatr Radiol 2011;41:1129-38.  Back to cited text no. 6
    
7.
Merheb M, Hourani R, Zantout MS, Azar ST. Endocrine dysfunction in a patient with PHACE syndrome, including port-wine stain of the right periorbital area. Endocr Pract 2010;16:255-9.  Back to cited text no. 7
    
8.
Poindexter G, Metry DW, Barkovich AJ, Frieden IJ. PHACE syndrome with intracerebral hemangiomas, heterotopia, and endocrine dysfunction. Pediatr Neurol 2007;36:402-6.  Back to cited text no. 8
    
9.
Savas Erdeve S, Ocal G, Berberoglu M, Siklar Z, Hacihamdioglu B, Evliyaoglu O, et al. The endocrine spectrum of intracranial cysts in childhood and review of the literature. J Pediatr Endocrinol Metab 2011;24:867-75.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11]



 

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