Rare Eye Findings in a Case of Sotos Syndrome

Objective: To report uncommon eye findings in a case of Soto’s Syndrome.


Introduction
Soto's syndrome as first described in 1964 by Soto et al. (1965).This syndrome is described by accelerated linear growth during early childhood and is associated with craniofacial and physical abnormalities, which may include macrodolichocephaly, scoliosis, and enamel hypoplasia (Inokuchiet al. 2001;Tatton-Brown and Rahman 2004;Baujat and Cormier-Daire 2007;Nalini and Biswas 2008).The cause of Soto's syndrome remains unknown, but most often, it occurs sporadically, though occasional cases with autosomal dominant inheritance have been reported (Winship 1985) Ocular manifestations of Soto's syndrome that have been published before include megalocornea, iris hypoplasia, cataracts,  (Michael T et al. 2000;Koenekoop et al. 1995).Various rare ophthalmological associations have been reported in the Western literature, and these include unilateral glaucoma, optic disc pallor, and retinal atrophy (Winship 1985;Michael T et al 2000).We unaware of previous reports of this finding and could find no reference to it, and to our best knowledge;-, this is the first reported keratoconus and anterior polar cataract case in patient with Soto's syndrome.

Case Report
A 10 year-old girl with recurrent fits and a known case of global developmental delay presented with a bilateral whitish reflex noted by parents for the past one year.She is a known case of Soto's syndrome under multidisciplinary care for the last 8 years.
Birth history revealed prematurity at 32 weeks with a birth weight of 2.5kg by emergency caesarian section due to preeclampsia.Birth length was between the 90th and the 97th percentile.Initial presentation to ophthalmology clinic at 2 years of age revealed no gross eye abnormality, and the bone age was estimated to be 3 years old.Regarding the anthropometric measurements, hand and feet length was between the 90th and the 97th percentile at 10 years;-_meanwhile, the head circumference was more than the 95th percentile at 5 years of age.There was no family history of consanguinity, mental deficiency, gigantism, or neurofibromatosis.She had delayed developmental milestones with poor scholastic performance.
General examination revealed typical dysmorphicfacies, prognathism, macrocephaly with tall narrow skull, flat nasal bridge, hypertelorism, apparent divergent squint, low set ears, and frontal bossing (Figure 1).The patient is able to walk but shows myriad of unpurposeful movement and history of frequent falls.Motor system revealed normal tone and power while reflexes were sluggish.Her mental capability was subnormal with associated poor hearing, and the speech was limited to mumbling sounds.Anterior segment examination revealed bilateral eye with dense anterior polar cataract (Figure 2).The dimensions of cornea were normal, but topographically keratoconus was present (Figure 3).There was an evidence of Vogt striae in the right eye but none in the left.There was no anterior segment dysgenesis seen and angles were open gonioscopically.Fundoscopy revealed healthy optic disc with cup-disc ratio of 0.5 with a normal macula, and there was no abnormal retinal pigmentary changes observed.Cyclorefraction postoperatively was noted as RE+2.00/-4.75x 180 and LE +2.50/-3.50x 160.K-reading showed 47.73 diopters in the right eye, but the left showed 46.00 diopters.(Figure 4).MRI brain showed enlargement of lateral ventricles and no evidence of hydrocephalus.(Figure 5).The pituitary gland was normal.An electroencephalogram also revealed abnormality with highly recurrent spike, poly-spike, and sharp waves.There was no raised T4 and other laboratory investigations were essentially normal.Our patient has undergone uneventful bilateral lens aspiration with intraocular lens implantation.Her visual acuity has improved from 6/60 to 6/9 in both eyes, with N6 and residual astigmatism.

Discussion
Soto's syndrome also known as cerebral gigantism is a rare disorder of growth and development with characteristic facial gestalt, non-progressive neurologic disorder, and normal endocrine function (Nalini A 2008).Aapproximately, 1 in 5,000 or 0.02% of 4,400 people in the United States have Soto's syndrome which includes reported cases and undiagnosed cases.From our MEDLINE search, the exact prevalence still remains doubtful.It is a non-hormone mediated accelerated growth disorder, which mimics pituitary gigantism, but with no neuro endocrine dysfunction (Hook EB 1967;Nalini A 2008).Large birth size with marked linear growth in the first few years of life, advanced bone age, and developmental delay are major diagnostic features in the syndrome- (Cole TR et al 1994).Our patient had typical clinical features with additional associations.
Many published articles have reported cataracts, and interestingly nuclear and cortical cataracts have been described but not polar cataract.Yeh et al. (1978) has described cortical cataracts as early as 1978, and Koenekoop et al. (1995) described nuclear cataracts in 1995- (Michael T et al 2000).
In a study performed on a large population from several colleges and schools of optometry and various clinics of optometrists and ophthalmologists, it was found that moderate-to-high refractive error, nystagmus, and strabismus were commonly associated with Soto's syndrome (Maino DM et al 1994).Our patient, in addition, had the rare association of keratoconus.
The patho-physiology is not well understood, although it is attributed to disordered collagen and elastin synthesis, and shares a common pathway with various syndromes like Beckwith-Wiedemann, Klippel-Feil, Trenauney, and Weavers syndromes (Douglas et al. 2003;Nalini and Biswas, 2008).The four major diagnostic criteria were established in 1994 by Cole and Hughes (1994) based on the systematic assessment of 41 typical cases: overgrowth with advanced bone age macrocephaly, characteristic facial appearance, and learning difficulties.(Geneviève Baujat 2007;Cole TR 1994).These clinical criteria remained the cornerstone for the diagnosis of Soto's until 2002.Discovery of a mutant gene Nuclear SET Domain 1 (NSD1) is currently accepted as the cause of this disorder (Douglas et al. 2003 and2005).Tatton-Brown ( 2004) analysed clinical features of a large series of more than 200 Soto's syndrome cases with proven abnormalities in NSD1and also reported possible link with toxaemia in pregnancy which was evident in our patient's history (Geneviève Baujat 2007; Opitzet al 1998).Unfortunately, no genetic karyo typing was performed on our patient.
Our report provides additional evidence of other rare ophthalmological association with Soto's Syndrome.Even though this is a single case presentation, it is important to highlight to the managing ophthalmologists that keratoconus and polar cataract could possibly be rare ocular features of this syndrome.This condition definitely warrants an early detection and careful monitoring.Appropriate treatment should be instituted to restore their best visual acuity.

Conclusion
Although relatively few descriptions of ocular findings are found in the existing literature, our report provides additional evidence that these patients can develop treatable ocular problems (Michael T et al 2000).These patients should be examined routinely to allow for early detection and treatment of potential ocular problems;keratoconus and cataract.This ultimately would be invaluable in the prevention of amblyopia.

Figure 2 :
Figure 2: Polar Cataract in the Patient's Right Eye.