Parry–Romberg syndrome (PRS) is a rare condition characterized by progressive facial hemiatrophy. The exact incidence and prevalence are unknown.1 Initially described by Parry2 in 1825 and further detailed by Romberg3 in 1846, PRS is characterized by progressive hemiatrophy of facial structures including the skin, subcutaneous tissue, muscle, and bone of one side of the face. PRS usually begins during the first or second decade of life, is more common in women (3:2 ratio), and may be more common on the left side.1 Although its etiology is unknown, contributing factors may include a vascular shunt, viral infection, and auto-immune antibodies.4 Marked variation in initial presentation and disease course eventually produce asymmetry with involvement of orbital fat, muscle, and other soft tissues on one side. The signs of PRS have been attributed to pathologic changes in soft tissue, atrophy of the orbital fat producing enophthalmos, or mechanical restriction from fibrosis, rather than from nerve damage.5 A recent clinicopathological case report documented fibrosis of extraocular muscle in a patient with PRS who presented with diplopia.6 We describe the following cases of PRS with abnormal eye movements to show the variable course.
A 23-year-old woman presented with horizontal diplopia worse on left gaze. This was initially attributed to a left sixth-nerve palsy by a strabismus specialist. Gadolinium-enhanced magnetic resonance imaging (MRI) of the brain and orbits with particular attention to the course of the left sixth nerve was read as normal. For incomitant esotropia, she underwent recess/resect surgery followed by a full tendon transposition of both vertical rectus muscles to the lateral rectus muscle. When she developed left upper eyelid ptosis, she sought neuro-ophthalmic consultation.
Her visual acuity was 20/20 in both eyes. Visual fields (Humphrey 24-2), pupils, retina, and optic nerves were normal. She had 2-mm ptosis of the left upper eyelid, exaggerated by her diplopia avoidance. Other tests of eyelid function were negative, including eyelid fatigue test, eyelid twitch sign, sleep test, Tensilon test, ice test, and acetylcholine receptor antibodies. The esotropia worsened with measurements increasing to 16 prism diopters in primary gaze and to 40 prism diopters on left gaze. Facial sensation was decreased on the left in the V2 distribution. Reevaluation of the MRI revealed wasting of the left facial muscles of expression and mastication, including temporalis, decreased superficial connective tissue, and fat on the left side of the face and edema in left extraocular muscles (Figs. 1 and 2). These findings were also seen on review of the previous “negative” MRI.
Figure 1. Coronal magnetic resonance imaging (MRI) of case 1 with contrast showing hemifacial wasting, including both the left lateral rectus and masticatory muscles. The lateral rectus and masticatory muscles on the right appear normal, but these muscles on the left had been largely replaced by fat. This difference was also visible in the initial T1 MRI in June 2004 (A) and final T2 MRI in October 2006 (B).
Figure 2. (A) Axial T1 magnetic resonance imaging of case 1 with contrast showing hemifacial wasting in June 2004, most notably of the left temporalis and pterygoid muscles. The temporalis and pterygoid muscles on the right are normal, but the left temporalis has been largely replaced by fat and the left pterygoid is atrophic. (B) Axial T2 magnetic resonance imaging (October 2006) with contrast showing hemifacial wasting, most notably of the left lateral rectus muscle, which had been largely replaced by fat.
She developed progressive left hemifacial weakness and left hemifacial atrophy. She underwent a frontalis suspension but still experienced ptosis and diplopia despite prism glasses and Botox injections (Allergan Inc., Irvine, CA).
A 28-year-old woman complained of horizontal diplopia for 7 years. The patient’s family had noted facial asymmetry and a left head turn, which placed her in perpetual right gaze. Her facial defect progressed over 2 years and then stabilized, leaving her with an ocular motor defect in the right eye, involving the right medial rectus and right inferior rectus muscles. The right eye was exotropic and there was severe limitation of adduction so that the eye did not even cross the midline.
The visual acuity, color vision, pupils, and visual fields were normal. The right malar eminence was flattened. Right orbital atrophy resulted in proptosis.
A 69-year-old woman had wasting of her left face noted at age 4 years and was diagnosed as having PRS when she was in her twenties. Bone grafts from her hip had been used to reconstruct her face with a cosmetic result, although she wore a wig to cover her forehead and had a residual en coup de sabre lesion. En coup de sabre lesions are idiopathic lesions that resemble scars from sword injuries and have been associated with PRS (15 of 28 patients in one Mayo clinic study), although the exact relationship remains unclear.1,7 She did not complain of diplopia, but her examination revealed left hypertropia and incomitant esotropia of approximately 8 prism diopters. Visual acuity was 20/15 in the right eye and 20/20 in the left eye, with full visual fields (Humphrey 24-2) and color plates, but the palpebral fissures were 9 mm in the right eye and 12 mm in the left with some minimal exposure keratopathy in the left eye. Hertel exophthalmometry measured 2 mm of proptosis in the left eye. The fundus was normal with cup/disc ratio 0.3 in the right eye and 0.2 in the left eye, with normal vessels and maculae.
A 68-year-old woman had problems with alignment of her eyes since at least age 5 years with no diplopia or stereopsis. She was diagnosed as having PRS at age 51 years on presenting with right ptosis, enophthalmos, and restriction of up gaze. She was unable to look up even to midline at the time of diagnosis and had a right hypotropia measuring 50 prism diopters in primary gaze. Forced ductions were positive for restriction in up gaze on the right, suggestive of fibrosis of the right inferior rectus muscle. She had a 4-mm right enophthalmos and demonstrated alternate suppression on Worth 4-dot testing. She was treated with a right inferior rectus recession at that time. Eighteen years later, she still had a right hypotropia of 25 prism diopters in primary gaze that was worse on up gaze and an esotropia that was worse on right gaze. She has declined any further surgery.
We present four cases of PRS, all of whom had abnormal eye movements from extraocular muscle involvement. Our cases showed soft tissue and eye muscle defects in the distribution of muscles rather than cranial nerves. Diagnosis of PRS was delayed in case 1 because the patient initially presented with what appeared to be an isolated sixth nerve palsy. Although the pattern of defects at first suggested a cranial neuropathy, all of our patients’ abnormal eye movements can be explained by muscle fibrosis, visualized on the MRI of case 1 (Figs. 1 and 2).
Although two MRIs had been done with detailed attention to the sixth nerve, the MRIs were read as normal because the hemifacial atrophy was overlooked. The other signs of PRS were finally appreciated clinically, prompting review of the MRI showing the hemifacial atrophy. This case illustrates the importance of considering PRS in a patient with what looks like a chronic sixth nerve paresis.
Patients with PRS typically present with painless facial wasting beginning near the midline of the face. Although the syndrome is defined by facial atrophy, hemiatrophy can rarely occur in other areas of the body, including the trunk, extremities (ipsilateral or contralateral), salivary glands, tongue, and various other organs, including brain, ear, kidney, diaphragm, larynx, and esophagus.4 Ophthalmic manifestations have been reported to occur in between 10% and 40% of patients with atrophy of orbital fat causing enophthalmos as the most common finding.8,9 The patients described here had findings limited to the forehead, midface, and eye muscles. All of our patients had normal pupils.
Other ocular manifestations include eyelid atrophy, blepharoptosis, blepharophimosis, Horner syndrome, heterochromia, corneal endothelial failure, muscle paresis, phthisis, and various pupillary abnormalities.8,10 In one clinicopathologic case report of a woman with PRS who presented with worsening diplopia over a 12-year course, histological evaluation of the extraocular muscle showed fatty and fibrous connective tissue without any striated muscle fibers.6 Another case had forced ductions and generation testing showing restrictive strabismus without nerve paresis.5 Although visual loss is rare, at least one patient presented with progressive visual loss with eye pain, a dilated pupil, retinal vascular tortuosity, and an elevated optic disc.11 Coats’ disease has been associated with PRS in three cases.12,13 None of our patients suffered any visual impairment.
Neurologic complications include headache, seizures on the contralateral side, paresthesia, paresis, and trigeminal neuralgia.14 Case 1 developed partial epilepsy, which has been linked to PRS. Moss and Crikelair performed unilateral cervical sympathectomies on rats that lead to hemifacial atrophy, suggesting a sympathetic origin.15
Therapy is primarily surgical, with facial reconstruction using grafts of fat, dermis, fascia, bone, cartilage, alloplastic materials (such as polyethylene implants), or pedicle flaps. Liquid silicone injections have been tried with variable results.8 Methotrexate and topical steroids have been tried in response to questions about underlying autoimmune mechanism, but have not helped. Tetracycline and hydroxychloroquine and localized injections of lidocaine into the stellate ganglion have also all been tried without success.1,16
We present four patients diagnosed as having PRS who presented with oculomotor defects. The variability in presentation of PRS can lead to a delay in both diagnosis and treatment, as evidenced by case 1. Clinicians should include PRS in the differential diagnosis of oculomotor abnormalities with atypical patterns and unknown etiology.