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 Table of Contents    
CASE REPORT
Year : 2014  |  Volume : 7  |  Issue : 2  |  Page : 69-71  

Cornelia de Lange syndrome with optic disk pit: Novel association and review of literature


1 Jasti V Ramanamma Children's Eye Care Center, Hyderabad, India
2 Nimmagadda Prasad Children's Eye Care Center, LV Prasad Eye Institute, Vishakhapatnam, Andhra Pradesh, India

Date of Web Publication19-Jul-2014

Correspondence Address:
Ramesh Kekunnaya
Department of Paediatric Ophthalmology, Strabismus and Neuro ophthalmology, Jasti V Ramanamma Childrens Eye Care Center, LV Prasad Eye Institute, KAR campus, LV Prasad Marg, Banjara Hills, Hyderabad - 500 034
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-620X.137149

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   Abstract 

Cornelia de Lange syndrome (CdLS), also called Brachmann-de Lange syndrome, is a multiple congenital anomaly syndrome characterized by a distinctive facial appearance, ophthalmological abnormalities, prenatal and postnatal growth deficiency, psychomotor delay, behavioral problems, and malformations of the upper extremities. Most common and consistent ophthalmic features reported are nasolacrimal duct obstruction, long and curly eyelashes, blepharitis, ptosis, synophrys, telecanthus, hypertelorism, microcornea, peripapillary pigment ring, and myopia. In this report we report a case of a 5-year old boy who presented to our institution with complaint of blurring of vision in the right eye since birth. A diagnosis of Cornelia de Lange syndrome was arrived at based on the characteristic external and ophthalmic examination. He was found to have a rare association of optic nerve head coloboma in the right eye and a novel finding of an optic disk pit in the left eye. The association of optic disk pit with CdLS has never been reported earlier. We aim to provide a thorough review of literature of this not so uncommon syndrome.

Keywords: Cornelia de lange syndrome, microcornea, optic disk coloboma, optic disk pit


How to cite this article:
Shenoy BH, Gupta A, Sachdeva V, Kekunnaya R. Cornelia de Lange syndrome with optic disk pit: Novel association and review of literature. Oman J Ophthalmol 2014;7:69-71

How to cite this URL:
Shenoy BH, Gupta A, Sachdeva V, Kekunnaya R. Cornelia de Lange syndrome with optic disk pit: Novel association and review of literature. Oman J Ophthalmol [serial online] 2014 [cited 2019 Dec 13];7:69-71. Available from: http://www.ojoonline.org/text.asp?2014/7/2/69/137149


   Introduction Top


Cornelia de Lange syndrome (CdLS) is a rare multisystem congenital disorder caused due to mutations in the NIPBL gene on chromosome 5p13. [1] Rarely, mutations in HDAC8, SMC1A, and SMCA3 have been found in smaller fraction of probands. [2],[3] Mental and physical retardation, microcephaly, hirsutism, characteristic facial and ophthalmologic abnormalities characterize the syndrome. Systemic abnormalities include cardiac defects, gastrointestinal anomalies, palatal abnormalities, genitourinary abnormalities, and hearing loss. [4] Common ophthalmic features are nasolacrimal duct obstruction, long and curly eyelashes, blepharitis, ptosis, synophrys, telecanthus, hypertelorism, microcornea, peripapillary pigment ring, and myopia. [5] We report a case of a 5-year old boy with CdLS with a rare association of optic nerve head coloboma in one eye and optic disk pit in other eye.


   Case Report Top


A five-year old boy presented to our institute with complaint of blurring of vision in the right eye since birth. There was no significant family history and the birth history was insignificant. He had mild psychomotor retardation. His best-corrected visual acuity was finger counting at 2 m in right eye and 20/30 in left eye. Cycloplegic refraction was +2.50 Dsph/-1.75 Dcyl × 60 in right and plano in the left eye. The external examination showed latent nystagmus and dissociated vertical deviation in the right eye. Other features included moderate ptosis in right eye, synophrys, long and curly eyelashes, crescent shaped mouth with thin down turned lips, low philtrum, and low set ears [Figure 1]. The anterior segment examination showed microcornea (horizontal visible corneal diameter = 9.5 mm) in the right eye and was unremarkable in the left eye. There was relative afferent pupillary defect in the right eye. Fundus examination revealed choroidal coloboma involving the optic disk and inferonasal peripapillary area in the right eye along with peripapillary pigment ring [Figure 2]. Fundus examination in the left eye revealed optic disk pit with cup disk ratio of 0.3:1 and peripapillary pigment ring [Figure 3]. Rest of the fundus was within normal limits in both eyes. A diagnosis of Cornelia de Lange syndrome with right optic disk coloboma and left optic disk pit with right eye dense amblyopia was made. The patient was prescribed spectacles and advised left eye part time occlusion therapy.
Figure 1: Face profile of the patient showing characteristic facial features and moderate ptosis, microcornea, synophrys, long and curly eyelashes

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Figure 2: OD Retcam image of the patient showing coloboma involving the optic disk and inferonasal peripapillary area with peripapillary pigment ring

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Figure 3: OS Retcam image showing optic disk pit with cup disk ratio of 0.3 and peripapillary pigment ring

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   Discussion Top


Cornelia de Lange syndrome (CdLS), also called Brachmann-de Lange syndrome, is a multiple congenital anomaly syndrome characterized by a distinctive facial appearance, ophthalmological abnormalities, prenatal and postnatal growth deficiency, psychomotor delay, behavioral problems, and malformations of the upper extremities. [5] The incidence is variable, ranging from 1:30,000 to 1:50,000 in different population groups. [5] Although autosomal dominant cases have been reported, most cases seem to be sporadic. Recent studies have demonstrated mutations in the NIPBL gene on chromosome 5p13 cause CdLS. [4],[6] There is no racial predilection. It is slightly more common in females than in males with a ratio of 1.3:1. A genetic study was not done in our case, as the child fulfilled the diagnostic criteria given by CdLS foundation, Inc. [7] This included facial features (synophrys, long and curly eyelashes, downturned lips, and low philtrum), major development criteria (development delay and learning disability) and major behavioral criteria (aggression, autistic like features and attention deficit hyperactivity disorder). The most common ophthalmological findings mentioned in the literature in the largest study to date, published by Jaffe et al., are synophrys, long arcuate eyelashes, hypertelorism, telecanthus, myopia, ptosis, strabismus, microcornea, astigmatism, and nystagmus. [8] Our patient had ptosis, synophrys, long arcuate eye lashes, microcornea, astigmatism, and nystagmus which was consistent with the findings reported by Jaffe et al. [8] Most common posterior segment finding in CdLS is the presence of peripapillary pigment ring. [8] Other reported rare findings are optic nerve atrophy, temporal pallor of the disk, optic nerve coloboma, and Coat's disease. Optic nerve coloboma, which was present in the right eye of our patient, has been reported only a couple of times in the literature to the best of our knowledge. [9] The present patient had an optic disk pit in the left eye. To the best of our knowledge the association of optic disk pit with CdLS has never been reported before. The optic disk pit may be associated with sub-retinal fluid (SRF) and neuro-sensory detachmet (NSD) causing diminished vision. However, our patient had no SRF/NSD associated with optic disk pit. The nipped-B gene which is implicated in CdLS is involved in notch signaling. Another notch signaling gene, JAG1, is implicated in Alagille syndrome, which is characterized by optic disk anomalies in up to 76% of cases. [5],[10] Hence the optic disk anomalies in CdLS like Alagille syndrome may be due to mutations in the NIPBL gene.

Our patient had an associated dense amblyopia in the right eye and was advised occlusion therapy. Occlusion therapy however was discontinued owing to no improvement in visual acuity after 3 months of therapy. Aggressive behavior and unwillingness to wear the prescribed glasses with patching is seen in children with CdLS and unsuccessful occlusion therapy for amblyopia has been reported. [9]

Children with Cornelia de Lange syndrome are often diagnosed by pediatricians and they usually have an associated mental and physical development lag. The spectrum of this disease is variable; a careful and detailed examination with stress on the important diagnostic facial features has to be done in order to reach a diagnosis. The ophthalmological findings in CdLS are variable. Only a few fixed ophthalmic features have yet been identified of which optic nerve head coloboma has been rarely reported. Optic disk pit has never been reported previously in association with CdLS to the best of our knowledge. Optic disk pit may be associated with SRF and NSD. Hence a careful examination should be done to minimize the possible development of complications and improve the quality of life. A multidisciplinary approach involving pediatrician, ophthalmologist, child psychologist, and rehabilitation is required for the management of these cases.



 
   References Top

1.Krantz ID, McCallum J, DeScipio C, Kaur M, Gillis LA, Yaeger D, et al. Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B. Nat Genet 2004;36:631-5.  Back to cited text no. 1
    
2.Deardorff MA, Bando M, Nakato R, Watrin E, Itoh T, Minamino M, et al. HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. Nature 2012;489:313-7.  Back to cited text no. 2
    
3.Deardorff MA, Kaur M, Yaeger D, Rampuria A, Korolev S, Pie J, et al. Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation. Am J Hum Genet 2007;80:485-94.  Back to cited text no. 3
    
4.Beck B, Fenger K. Mortality, pathological findings and causes of death in the De-Lange syndrome. Acta Paediatr Scand 1985;74:765-9.  Back to cited text no. 4
[PUBMED]    
5.Uzun H, Senses DA, Ulba M, Kocaba K. A newborn with Cornelia de Lange syndrome: A case report. Cases J 2008;1:329.  Back to cited text no. 5
    
6.Tonkin ET, Wang TJ, Lisigo S, Bamshad MJ, Strachan T. NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in cornelia de Lange syndrome. Nat Genet 2004;36:636-41.  Back to cited text no. 6
    
7.CdLS foundation. Connecticut: The Association; 2010. Cornelia de Lange Syndrome (CdLS) Diagnostic Criteria Checklist. Available from: http://www.cdlsusa.org/docs/cdls-diagnostic-checklist.pdf [Last accessed on 2013 Oct 20].  Back to cited text no. 7
    
8.Jaffe TW, Shin J, Perruzza E, Abdolell M, Jackson LG, Levin AV. ophthalmologic findings in the cornelia de lange syndrome. J AAPOS 2005;9:407-15.  Back to cited text no. 8
    
9.Kim IT, Park JW, Choi WC. A Korean case of cornelia de lange syndrome. Korean J Ophthalmol 2005;19:153-5.  Back to cited text no. 9
    
10.Hingorani M, Nischal KK, Davies A, Bentley C, Vivian A, Baker AJ, et al. Ocular abnormalities in alagille syndrome. Ophthalmology 1999;106:330-7.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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