Ocular features in a patient presenting with a rare combination of multiple phakomatoses
- 1 Department of Glaucoma, Aravind Eye Hospital, Madurai, Tamil Nadu, India
- 2 Department of Vitreoretinal services, C.L. Gupta Eye Institute, Moradabad, Uttar Pradesh, India
- Correspondence to Dr Piyush Kohli; kohli119@gmail.com
Abstract
Phakomatoses are a group of congenital disorders characterised by hamartomatous lesions of the skin as well as the central and peripheral nervous systems. The presence of naevus flammeus or port-wine stain is a characteristic feature of many such disorders including Sturge-Weber syndrome (SWS), Klippel-Trenaunay syndrome (KTS) and Phakomatosis pigmentovascularis (PPV).
We describe the ocular findings in a patient with coexisting PPV, SWS and KTS
Background
Phakomatoses (neurocutaneous syndromes) are a group of congenital disorders characterised by hamartomatous lesions of the skin as well as the central and peripheral nervous systems. The presence of naevus flammeus or port-wine stain (PWS) is a characteristic feature of many such disorders including Sturge-Weber syndrome (SWS), Klippel-Trenaunay syndrome (KTS) and Phakomatosis pigmentovascularis (PPV).1
SWS is characterised by congenital hamartomas of the eye (choroidal haemangioma), the skin (PWS) and brain (leptomeningeal haemangioma with intracranial calcification). The patients may present with glaucoma, seizures and other neurological disorders. The classic triad associated with KTS consists of cutaneous and visceral haemangiomas, venous varicosities and soft-tissue or bone hypertrophy. PPV is defined by the presence of cutaneous vascular malformation (nevus flammeus) and pigmentary nevi involving either the eye alone (ocular melanocytosis) or along with face and body (oculodermal melanocytosis). All these three congenital disorders may rarely coexist in a patient.1 2
We describe the ocular findings in a patient with coexisting PPV, SWS and KTS.
Case presentation
A man in his 30s presented with painless gradual loss of vision in his left eye since last 4–5 years. He was born of a non-consanguineous marriage and had no significant family history.
His best-corrected visual acuity (BCVA) was 20/20 in the right eye and no perception of light in the left eye. His intraocular pressures (IOP) were 24 and 7 mm Hg, respectively. Examination of the visual axes showed a left divergent squint along with relative afferent pupillary defect in the left eye. Anterior segment examination showed bluish-black scleral pigmentation, and densely pigmented iris in both the eyes; along with dilated prominent episcleral vessels and complicated cataract in the left eye (figure 1A,B). Gonioscopy revealed open angles and increased trabecular pigmentation of meshwork in both the eyes. Posterior segment examination of the right eye showed a cup-disc ratio of 0.7 with thinning of the inferior neuroretinal rim, tortuous vessels with no other pathology like choroidal nevus or haemangioma (figure 2A). Posterior segment examination of the left eye was not possible due to the presence of dense white cataract.
(A) Slit lamp photograph of the right eye showing bluish-black scleral pigmentation and densely pigmented iris; (B) slit lamp photograph of the left eye showing bluish-black scleral pigmentation, densely pigmented iris, dilated prominent episcleral vessels and complicated cataract and (C) clinical photograph showing well-defined erythematous non-blanchable patch (port-wine stain) over the forehead, cheek and upper jaw of the left side; hypertrophy of left side of the face and an enlarged upper left lip.
(A) fundus photograph of right eye showing a cup-disc ratio of 0.7 with thinning of the inferior neuroretinal rim; (B) spectral-domain optical coherence tomography retinal nerve fibre layer (RNFL) analysis revealed inferior RNFL thinning; (C) enhanced depth imaging OCT showed choroid thickness of 650 μm and (D) B-scan ultrasonography of the left eye showing diffusely thickened choroid along with retinal detachment suggestive of choroidal haemangioma.
General examination revealed a well-defined erythematous non-blanchable patch (PWS) over the forehead, cheek and upper jaw of the left side of his face (first and second division of the trigeminal nerve); facial dysmorphism, hypertrophy of left side of the face and an enlarged upper left lip (figure 1C). There were no abnormalities in his oral mucosa. There was diffuse dermal melanosis over his neck as well as both sides of his chest, upper back and upper limbs. Lower limbs showed the presence of swollen, twisted blood vessels bulging under the skin surface on the right leg suggestive of varicose veins. However, there was no hypertrophy of any lower limb (figure 3).
Clinical Photographs showing (A) diffuse dermal melanosis on both sides of the upper back and both upper limbs; (B) diffuse dermal melanosis on neck and (C) swollen, twisted blood vessels bulging under the skin surface (varicose veins) on the right leg with no hypertrophy of either limb.
Investigations
Spectral-domain optical coherence tomography (Heidelberg Retina Tomograph, Heidelberg Engineering, Germany) retinal nerve fibre layer (RNFL) analysis of the right eye revealed inferior RNFL thinning (figure 2B). Enhanced depth imaging OCT (EDI-OCT) of the right eye showed a choroid thickness of 650 μm (figure 2C). Visual fields analysis (24–2 Swedish Interactive Threshold, Algorithm Standard, Humphrey Field Analyzer, Humphrey Instruments, Dublin, California, USA) of the right eye revealed a corresponding superior arcuate scotoma. B-scan ultrasonography of the left eye showed diffusely thickened choroid along with retinal detachment (RD) (figure 2D).
MRI and angiography of the brain showed no evidence of cerebral calcification, cerebral atrophy or leptomeningeal angiomas. Abdominal ultrasonography also revealed no abnormalities.
Differential diagnosis
The patient had multiple overlapping syndromes. He was diagnosed as bilateral PPV, KTS and SWS with complicated cataract, choroidal haemangioma and RD in the left eye.
Treatment
He was advised to use topical latanoprost drops (0.005%) to be used only at night in his right eye. After discussion with the patient, treatment was deferred in the left eye due to nil visual prognosis.
He was advised to undergo check-up with a surgeon for varicose veins.
Outcome and follow-up
One month after starting the medications, IOP in his right eye reduced to 14 mm Hg. He maintained his BCVA, while his IOP was well controlled at 1-year follow-up. He has been advised to come for regular follow-up to monitor IOP and look for early signs of choroidal melanoma.
Discussion
PPV was originally described by Ota et al.3 It was originally classified into four types on the basis of the pigmentary nevi. Cutaneous vascular malformation, that is, nevus flammeus is present in all the cases. Type I is characterised by an epidermal nevus, that is, benign patch of skin caused by an overgrowth of epidermal cells; type II is characterised by dermal melanocytosis or Mongolian spot, that is, grey–blue areas of discolouration with or without nevus anemicus that is, hypopigmented cutaneous macules; type III is characterised by nevus spilus, that is, multiple pigmented macules or papules within a pigmented patch with or without nevus anemicus; while type IV is a combination of type II and type III. All the four types are subgrouped into ‘type a’ and ‘type b’ on the basis of the absence or presence of systemic organ involvement, respectively. Type II has been found to be the most common form.1 2 Happle later modified the classification into three types, that is, cesioflammea, spilorosea and cesiomarmorata. Phakomatosis cesioflammea is identical to types II PPV; phakomatosis cesiomarmorata represents the traditional types III PPV, while phakomatosis spilorosea describes the type V PPV, that is, cutis marmorata telangiectatica congenita (marbled-like or fishnet-like skin patches).4 Ocular features include hyperpigmentation of conjunctiva, sclera, episclera, corneal stroma, iris, trabecular meshwork and choroid. The mechanisms involved in the pathogenesis of glaucoma may include incomplete development of the trabecular meshwork or increased trabecular pigmentation.1 2 Our patient had features of types IIb PPV or Phakomatosis cesioflammea.
PPV, especially type II or cesioflammea form, may overlap with SWS and KTS.1 2 A somatic mutation in the GNAQ gene has been reported in such patients.2 Our patient presented had cutaneous facial angioma and glaucoma in the absence of leptomeningeal angioma. Hence, he was diagnosed as type II SWS according to the Roach diagnostic scale.5 Both the syndromes can present with diffuse choroidal haemangioma and glaucoma.1 Our patient presented with complicated cataract, thickened choroid and RD in the ipsilateral eye (ie, the left eye), which may be attributed to long-standing untreated diffuse choroidal haemangioma. Diffuse choroidal haemangioma can be treated with photodynamic therapy and external beam radiotherapy.1 However, we avoided any treatment as the patient did not have any perception of light. EDI-OCT of the contralateral eye (ie, the right eye) showed increased choroidal thickness. Earlier studies have also shown that the choroidal thickness may increase not only in the affected eye but also the unaffected eye.6 7 Abdolrahimzadeh et al proposed that the vessel calibre modulation caused by the GNAQ gene mutation could lead to increased choroidal thickness of the unaffected eye.6
The mechanisms involved in the pathogenesis of glaucoma may include malformation of the anterior chamber angle, vascular malformations or raised episcleral venous pressure.1 Glaucoma in such eyes is often unresponsive to medical treatment may need surgical intervention at some point of time.1 8 IOP in the eye ipsilateral to PWS (ie, the left eye) was low due to the presence of RD, while it was controlled on one drug in the contralateral eye (ie, the right eye).
Our patient presented with overlapping features of PPV, SWS and KTS. Cases with overlapping PPV and SWS or SWS and KTS have been reported in literature.1 2 However, less than 10 cases of PPV associated with both SWS and KTS have been reported.9–16 Such patients are at a high risk of developing choroidal melanoma. This may be attributed to the GNAQ gene mutation, which is seen in the PWS of SWS and KTS as well ocular melanocytosis, optic disc melanocytoma and uveal melanoma.17 Shields et al suggested that such patients should undergo dilated fundus examination once or twice a year to screen for choroidal melanoma.17 The anomalous venous network predisposes individuals to thromboembolic events.18 A high degree of suspicion should be maintained to identify the syndromic associations in such patients at an early age. Management of such patients requires a thorough systemic workup and multidisciplinary approach to avoid life-threating complications.
Learning points
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Port wine stain can be the presenting features in multiple phakomatoses including Sturge-Weber syndrome (SWS), Klippel-Trenaunay syndrome (KTS) and Phakomatosis pigmentovascularis (PPV).
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Patients may have combined features of multiple phakomatoses as SWS, KTS and PPV may coexist in a single patient.
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Management of such patients requires a thorough systemic workup and multidisciplinary approach to avoid life-threating complications.
Ethics statements
Patient consent for publication
Footnotes
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Contributors VAS contributed to the conception and design, acquisition of data,drafting of the article or revising it critically for important intellectual content. PK contributed to the conception and design, acquisition of data,drafting of the article or revising it critically for important intellectual content. CM contributed to the conception and design, acquisition of data,drafting of the article or revising it critically for important intellectual content. KM contributed to the conception and design, acquisition of data,drafting of the article or revising it critically for important intellectual content.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
References
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