2001-11-28-17 PHACES syndrome with cerebellar hemihypoplasia © Gonçalves www.thefetus.net/
PHACES syndrome with cerebellar hemihypoplasia
Luís Flávio Gonçalves, MD1, Eugênio Grillo MD2
1Clínica Materno-Fetal, Florianópolis, Brazil; Universidade do Vale do Itajaí, Florianópolis, Brazil2Hospital Infantil Joana de Gusmão, Florianópolis, Brazil
This is a third trimester fetus with cerebellar hemihypoplasia. At birth the baby had an extensive facial hemangioma. The final diagnosis for the case was PHACES syndrome1-5
- posterior fossa malformations (74%), most commonly of the Dandy-Walker variant;
- hemangiomas (41%) (especially large, plaquelike, facial lesions or in the airways, possibly causing dyspnea);
- arterial anomalies (21%) (in particular of the central nervous system vasculature, hypoplasia of the carotid-vertebral trunk);
- cardiac anomalies (26%) and coarctation of the aorta;
- eye abnormalities (23%) (congenital cataracts, glaucoma, choroidal hemangioma and a papillary abnormality) ; and
- sternal anomalies or cleft and/or supraumbilical raphe
Other anomalies include lingual thyroid1
The cardinal finding of PHACES is the posterior fossa anomalies and facial hemangiomas. Most affected children have only one extracutaneous manifestation3. The lesions tend to be ipsilateral to the hemangioma.
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 Mar;132(3):307-11
2 Metry DW, Hebert AA.Benign cutaneous vascular tumors of infancy: when to worry, what to do. Arch Dermatol 2000 Jul;136(7):905-14
3 Metry DW, Dowd CF, Barkovich AJ, Frieden IJ.The many faces of PHACE syndrome.J Pediatr 2001 Jul;139(1):117-23
4 Buzenet C, Hamel-Teillac D, Acar P, Becquet F, Curan D, Michaud V, Sidi D, De Prost Y.Facial hemangioma associated with arterial anomalies, coarctation of the aorta, and eye abnormalities: PHACES syndrome. Ann Dermatol Venereol 2000 Mar;127(3):292-5
5 Boulinguez S, Teillac-Hamel D, Bedane C, Bennaceur S, De Prost Y.Cervicofacial hemangioma and a minor sternal malformation: inclusion in PHACES syndrome? Pediatr Dermatol 1998 Mar-Apr;15(2):119-21
The association of cerebrovascular and facial arterial anomalies and hemangiomas was first noticed by Pascual-Castroviejo (Pascual-Castroviejo, 1978). Subsequently, Reese et al. (Reese et al., 1993) described the association of facial hemangiomas with Dandy-Walker and other posterior fossa malformations. The acronym PHACE was proposed by Frieden et al. (Frieden et al., 1996).
Isolated cerebellar lesions observed during routine ultrasound scans may be the only prenatal finding of the syndrome. Nonetheless, we feel it is important to consider the possibility of PHACE syndrome in the differential diagnosis of cerebellar lesions, not only to minimize parental psychological impact caused by the visualization of large facial hemangiomas unsuspected before birth, but also to be aware and specifically search for the associated malformations.
We describe a fetus with an apparently isolated cerebellar abnormality observed during routine prenatal ultrasound, later diagnosed as PHACE syndrome.
A 30 year-old G1P0 patient was referred at 29 weeks for a routine ultrasound scan. Cross-sectional images of the posterior fossa demonstrated absence of the left cerebellar hemisphere and vermis (Figure 1). No other abnormalities were observed. Fetal biometry was within normal limits for the estimated gestational age. Scans performed at 31, 35 and 39 weeks did not show progression of the lesion. The subsequent course of pregnancy was uneventful.
A female infant was delivered at term. She was mildly large for gestational age (birth weight 4350g). The physical examination was normal at birth except for a large flat angioma covering the left side of face and neck, sparing the mandibular region. There were also very discrete angiomas in the left iris. Neurologic examination was normal. A cranial ultrasound scan confirmed the posterior fossa abnormality and did not disclose any anterior fossa abnormality. During the first few weeks of life, the angioma became prominent, occluded the left eyelid fissure and produced wounds in lips, impairing breast-feeding. A tuberous–cavernous hemangioma was diagnosed. In spite of treatment with steroids and interferon, the lesions progressed with destruction of the nasal septum. Ophthalmologic evaluation ruled out glaucoma. At 6 months of age, a chest X-ray with enhanced esophagus showed mediastinal enlargement with right deviation of esophagus and trachea suggesting intrathoracic extension of angioma, without respiratory symptoms. At the end of the first year of age a mild global developmental delay has been observed without any focal or cerebellar dysfunction.
Dandy-Walker malformation, Dandy-Walker variant and mega cisterna magna are the most common posterior fossa abnormalities diagnosed with prenatal ultrasound. Dandy-Walker malformation has an estimated incidence of 1/30,000 births and is characterized by enlarged posterior fossa, complete or partial agenesis of the cerebellar vermis and elevated tentorium. Dandy-Walker variant is defined as variable hypoplasia of the cerebellar vermis with or without enlargement of the posterior fossa and a mega cisterna magna is characterized by enlarged cisterna magna with integrity of both cerebellar vermis and fourth ventricle. The precise incidence of the last two anomalies is unknown (Pilu et al., 2001).
This case is the first, to our knowledge, to report the unilateral absence of a cerebellar hemisphere and vermis diagnosed with prenatal ultrasound in association with a large hemifacial hemangioma found after birth and the final diagnosis of PHACE syndrome. Prenatal counseling was difficult because of the lack of information regarding the prenatal findings in the medical literature. It was also incomplete because it was entirely based on the assumption that cerebellum was the only organ affected.
When the neonate was first examined by the neurologist, The first diagnostic impression was Sturge-Weber syndrome (STW), because of the extensive hemifacial hemangioma observed after birth. However, the typical facial anomaly in STW is a port-wine stain (capillary malformation) rather than a hemangioma and the primary nervous system abnormality is a leptomeningeal vascular malformation. Posterior fossa abnormalities are not part of the typical clinical picture of STW.
PHACE syndrome is characterized by the presence of: 1) hemifacial hemangioma in all cases; 2) Dandy-Walker or other posterior fossa anomalies in 74% of the cases; 3) arterial anomalies (41%); 4) cardiac or aortic malformations (26%); ophthalmologic anomalies (23%); and 7) ventral defects in 7% of the cases (Frieden et al., 1996).
The disease spectrum has been extensively reviewed by Metry et al. (Metry et al., 2001). Females are affected in 87 to 100% of the cases (Frieden et al., 1996; Metry et al., 2001). The hemangioma is usually large, segmental and distributed along trigeminal division V1 dermatome in 75% of the cases. When a sternal cleft or supraumbilical raphe is present, distribution along the trigeminal division V3 dermatome is more common. Left hemifacial hemangiomas predominate, followed by right sided and bilateral lesions. The initial presentation is usually a “plaque-like” hemangioma. In one third of the cases, the upper trunk and extremities may also be affected. Intracutaneous hemangiomas occur in 22% of the cases and have been reported in the subglottic airway, brain, bowel, liver, lung, pancreas and thyroid gland. The characteristic brain anomaly is a Dandy-Walker malformation, followed by hypoplasia or agenesis of the cerebellum, cerebellar vermis, corpus callosum, cerebrum and septum pellucidum. Aneurysmal dilatations and anomalous branches of the carotid arteries are the most common associated arterial malformations. The single most common cardiac defect is coarctation of the aorta, although other cardiac anomalies have also been reported. Ocular findings, when present, are usually ipsilateral to the facial hemangioma and include: microphthalmia, optic atrophy, iris vessel hypertrophy, iris hypoplasia, optic nerve hypoplasia, congenital cataracts, sclerocornea, lens coloboma, and exophthalmos. It is noteworthy that, in 70% of the cases, only one extra cutaneous manifestation of the syndrome is present.
The predominance of the female gender led some to speculate that PHACE syndrome might represent an X-linked dominant condition with lethality in males (Gorlin et al, 1994). The pathogenesis of the PHACE syndrome is still unknown, but is thought to represent a developmental field defect occurring during weeks 6 to 8 of development (Reese, 1993; Frieden, 1996).
In one large series, ninety percent of the patients with a combination of structural cerebral and arterial anomalies developed secondary neurologic sequelae, characterized in the majority of the cases by developmental delay or unexplained seizures. Migraine headaches ipsilateral to the original site of the facial hemangioma have also been observed (Metry et al., 2001). The mild global developmental delay observed at one year of age in our case is not necessarily secondary to intracranial lesions. It could be related to treatment with steroids and interferon (Chang et al., 1997; Boon et al., 1999).
PHACES syndrome should be considered in the differential diagnosis of any child with a large hemifacial “plaque-like” hemangioma. For those who work with prenatal diagnosis, however, this will not be the typical presentation. Conversely, prenatal diagnosis of a posterior fossa anomaly should prompt the search for other findings outside the central nervous system, especially cardiac anomalies. We feel that parents should be at least informed of the possibility of the association with large facial hemangiomas in these cases in order to minimize the impact of seeing an unexpected, large facial lesion after birth.
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Coats DK, Paysse EA, Levy ML. PHACE: a neurocutaneous syndrome with important ophthalmologic implications. Ophthalmology 1999;106:1739-41.
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.
Gorlin RJ, Kantaputra P, Aughton DJ, Mulliken JB. Marked female predilection in some syndromes associated with facial hemangiomas. Am J Med Genet 1994;52:130-45.
Metry DW, Herbert AA. Benign cutaneous vascular tumors of infancy: what to worry, what to do. Arch Dermatol 2000;136:905-14.
Metry DW, Dowd CF, Barkovich AJ, Frieden IJ. The many faces of PHACE syndrome. J Pediatr 2001; 139:117-23.Pascual-Castroviejo I. Vascular and nonvascular intracranial malformations associated with external capillary hemangiomas. Neuroradiology 1978; 16:82-84.