Ocular manifestations in a case of progeroid syndrome

Progeria syndromes are very rare genetic diseases characterized by premature aging changes. There are several phenotypes and variables noted in literature in some cases difficult to specifically classify a specific syndrome. It occurs due to mutation in DNA repair genes. The most common ocular findings are loss of eyebrow and eyelashes, brow ptosis, lid margin changes, entropion, Meibomian gland dysfunction, severe dry eye, corneal opacity, cataract, poor mydriasis, and rod-cone dystrophy. We report this case with all the above ocular manifestations in 19year old teenager with additional finding being retinal detachment.

Progeroid syndromes are a cluster of genetic disorders characterized by various clinical features and phenotypes of physiological aging prematurely, some of which are even fatal. Ataxia-telangiectasia, Fanconi anemia, Bloom syndrome, Cockayne syndrome, Hutchinson-Gilford syndrome, Rothmund-Thomson syndrome, trichothiodystrophy, xerodermapigmentosum, and Werner syndrome are among some of progeria syndromes [1]. The derivation of the word progeria means ‘prematurely old’ in greek. It is caused by de novo dominant mutation in the LMNA gene (gene map locus 1q21.2) and characterized by growth retardation and accelerated degenerative changes of the skin, musculoskeletal and cardiovascular systems [2].

Classical Hutchinson-Gilford progeria syndrome is usually caused by a sporadic autosomal dominant mutation 6. There are a few atypical forms of progeria, also called non-classical progeria in which growth is less retarded, scalp hair fall off slowly, a progression of lipodystrophy is delayed, osteolysis is more visible with an exception in face and survival is observed mostly till adulthood [3].

Ocular manifestations in progeria syndrome i.e in classical variant are loss of eyebrows and eyelashes, poliosis, lagophthalmos, narrowing of the palpebral fissure, superior sulcus deformity, lid retraction, upper lid lag in downgaze, poor pupillary dilatation, cataract, etc..., [2].

In non-classical variant depending upon gene mutation and penetrance level ocular manifestations can range from lid abnormalities, dry eye, corneal opacity, poor mydriasis, cataract, pigmentary retinopathy, rod and cone dystrophy, optic atrophy etc..., [4].

In this study, we report 19 year old teenager with the non-classical progeroid syndrome and ocular manifestations associated with it. Consent was taken to examine and ethical clearance cleared from Department Head.

A 19-year-old teenager came to our OPD in Karwar Institute of Medical Sciences Karwar with complaints of diminution of vision right eye for 5 years gradually progressive aggravated during the last 6 months. The patient also complained of recurrent redness, watering, foreign body sensation, severe photophobia, and intolerance to sunlight for 5 years. The patient has a history of poor vision during school age and thus discontinued schooling at the 6^th standard. The patient doesn’t work for a living and stays inside the house regularly. The Patient also has loss of scalp hair, eyebrows, skin wrinkling and pigmentation, dental caries since 5 years.

According to parents, he was the first child of family, other 3 being younger sisters who are asymptomatic. Parents had non-consanguineous marriage. His antenatal, natal, and postnatal history were uneventful. He didn’t have significant health problems until the 6^th standard. Parents had earlier consulted many doctors but treatment history was not available. The patient had a history of seizures during childhood but no diagnosis of epilepsy was made. No history of hypertension, diabetes, or hyperlipidemia was diagnosed.

He was poorly built & nourished, and was conscious & oriented to time, place& person. His IQ was adequate. His height was 155 cm and weight 45 kg which was statistically less than average at this age indicating cachectic dwarfism. His head circumference was 54 cm. The skin was pale and aging signs like wrinkling and pigmentation were present. The face had hypopigmented spots in the malar area. There was generalized hair loss, loss of subcutaneous fat. The Musculoskeletal system showed osteoporosis changes in the X-ray. Cardiac and respiratory systems were normal. Neurological examination showed decreased muscle power grade 3-4 with brisk reflexes. There was a mild sensorineural hearing loss which was confirmed by the audiogram. All the signs pointed out to aging changes.

Extra Ocular manifestations noted were loss of eyebrow and eyelashes with few remaining which had poliosis. Excessive wrinkling of the forehead was noted. Inner canthal distance 40 mm, outer canthal distance 110 mm, inter-pupillary distance 76 mm, vertical palpebral fissure 10 mm, horizontal palpebral fissure 18 mm. There was no proptosis. Head posture, ocular posture, and extraocular movements were normal.

Lid changes included lid margin abnormalities, meibomian gland dysfunction, loss of eyelashes, mild grade 1 entropian, and no adequate tarsal support. Cyst of Zeiss was noted in the left lower eyelid. Conjunctiva dryness noted, Schirmer’s testreading was less than 3 mm indicating severe dry eye. Cornea had dry lusterless look, both eyes had inferior corneal opacity right more than left with 360 degree superficial vascularization in right cornea and 30 degrees in left cornea. Deep vascularization of 2 O’ clock hours was noted at 7 O’ clock position. Corneal opacity in right eye was involving pupillary area. Senilearcus changes were difficult to look up as cornea was vascularized. On staining punctuate corneal erosions noted. Corneal sensation was decreased. Anterior chamber was normal in depth. Iris was normal. Pupil was round, reacting to light, but RAPD grade 1 was noted in right eye. IOP was measured by tonopen and was normal and gonioscopy was unremarkable. Patient could perceive light in right eye, but had inaccurateprojection of rays. He could count fingers at half meter with his left eye. Colour vision and contrast sensitivity could not be tested because of poor vision. Dry refraction revealed no glow in right eye and dull glow in left eye.

Slit lamp examination after dilatation with tropicamide 0.8% and phenylephrine 5% revealed poor mydriasis. Right eye showed brown cataract and left eye showed grade 3 nuclear cataract. The Fundus could not be visualized the right due to corneal opacity and cataract. Ultrasound Bscan of right eye showed inferior RD. Left eye fundus revealed normal optic disc and dull foveal reflex with normal peripheral retina. OCT showed altered foveal contour, NSD noted completely temporal to disc, hyperreflective areas above RPE, and CMT being 357 microns. The cause of poor vision in left eye was unexplained but clinically rod-cone dystrophy was kept in mind as the probable diagnosis.

After complete ocular evaluation patient was referred to physician for complete diagnosis. Provisional diagnosis of non-classical variable penetrance Cockayne syndrome, a form of progeroid syndrome was made. But genetic testing was not done to confirm Cockayne syndrome. Hence based on the clinical feature it was difficult to diagnose exact subtype of progeria syndrome. Cockayne Syndrome Type 3, a milder form; and xeroderma pigmentosa-Cockayne syndrome (XP-CS) can be more likely in this case (Images 1-4).