Dr Nisha George , Sundaram Medical Foundation Children’s HospitalChennai

4 year old girl Opacity right eye 5 months Opacity left eye 3 months Keeping head flexed and eyes

closed 3 months

No history of trauma, feverNo seizures or alteration in consciousnessNo change in routine activity

Only child to parents in a consanguinous marriage (parents are cousins)

Born normally , Birth weight: 2750gmNeonatal period : Uneventful Not ‘loose’ on handlingDevelopment: Normal No significant past history

On examinationAlert, talks in response,Wt: 12.58Kg (3th cent) Ht: 100cm (50th cent), Arm span:100cmUS/LS ratio: 1:1 HC: 52cm , dolicocephalic Dysmorphism Flat facies, depressed nasal bridge, Hyperextensible joints- elbow, wrist , knee,

ankle

CNS examination: Normal sensorium- conscious , oriented,

clear speech Cranial nerves: Limited exam normal Motor system: Power 5/5 all four limbs Brisk DTRs Down going plantars

Sensory examination to touch and pain normal

Joint position sense normal

No cerebellar signsTorticollis presentWhen pulled up in the supine position no

head lag When lying supine head extends but child in

pain.

Investigations

Hb:11.4gm/dlWBC and platelet counts : normalElectrolytes: normalESR and CRP normalCPK normalANA and DSDNA negative

Ophthalmologic examinationPrevious examination: Blue sclera

Small cornea, dry mucosaCorneal opacities both eyesNormal fundusNormal intraocular pressures

ImagingMRI Brain: Atrophy of bilateral cerebellar hemispheres.

Involvment of bilateral posterior parietal and occipital lobes. Thinning of white matter of both areas.

128 slice CT angiogram: Normal

MRI cervical spine: Prominent dens mildly compressing on the cervico-medullary junction.

X- Ray Cervical spine: Evidence of atlanto axial subluxation

Connecting the dots…MicrocorneaCorneal opacitiesHyper extensible joints

Ehlers- Danlos syndrome

Brittle cornea syndrome Marfans syndrome Osteogenesis imperfecta

Ehlers- Danlos syndromeBrittle cornea syndrome

Ehlers-Danlos syndromeA group of related conditions with a common

decrease in the tensile strength and integrity of the skin, joints, and other connective tissues.

Edward Ehlers, a Danish dermatologist, in 1901 Henri-Alexandre Danlos, a French physician with

expertise in chemistry of skin disorders, in 1908. - Delineated the phenotype

‘Indian Rubber man’, The Elastic Lady," and "The Human Pretzel.”

Pathophysiology: Various abnormalities in the synthesis and

metabolismof collagen and other connective tissue proteins. 1. Collagen: Most abundant 29 genes / Located on 15 of the 24

chromosomes 19 identifiable forms of collagen molecules.2. Elastin: Elastin protein with microfibrillar array

(Cutis laxa/WS)3. Microfibrillar protein is fibrillin (Marfans )4. Proteoglycans - Glue of the connective tissue protein

The specific characteristics of a particular form of Ehlers-Danlos syndrome-tissue-specific distribution of various components of the extracellular matrix

Accurate clinical diagnosis primary means of identifying affected individuals.

50% do not have a type or form that can be classified easily on clinical basis

Ehlers-Danlos National Foundation (EDNF) in 1997.Type In

hPrev

Major Minor

Classic AD I/II Skin hyperextensibility,wide atrophic scars,joint hypermobility

Smooth, velvety skin; easybruising; molluscoidPseudotumors etc.

Hype mobility

AD III Skin involvement (soft,smooth and velvety),joint hypermobility

Recurrent joint dislocation;chronic joint pain, limb pain, or both; positive family history

Type I Prev

Major criteria Minor criteria

Vascular

AD IV Thin, translucent skin;arterial/intestinal fragilityor rupture; extensivebruising; characteristicfacial appearance.

hypermobile small joints;tendon/muscle rupture; clubfoot;early onset varicose veins;arteriovenous, carotid-cavernous etc.

Kyphoscoliosis

AR VI Joint laxity, severehypotonia at birth,scoliosis, progressivescleral fragility orrupture of globe.

Tissue fragility,easy bruising, arterial rupture,marfanoid,microcornea,osteopenia,positive familyhistory (affected sibling)

Arthrocalasia

AD V II A/B

Congenital bilateraldislocated hips,severe joint hypermobility,recurrent subluxations

Skin hyperextensibility,tissue fragility with atrophic scars,muscle hypotonia,easy bruising,kyphoscoliosis, mild osteopenia

Dermatosparaxis

AR VII C

Severe skin fragility;saggy, redundant skin

Soft, doughy skin; easy bruising; premature ruptureof membranes; hernias

Ehlers- Danlos and the corneaCommon ocular manifestations:Dry eyes, keratoconus, Epicanthal folds, high

myopia,Astigmatism, Strabismus, Ambylopia, blue sclera, microcornea

Serious ocular involvement:Dislocated lens, Retinal detachmentCorneal ruptureBrittle cornea syndrome

Peter Beighton, BJO 1970,54Sharma et al. Indian Jnl.of Opthalmology 2003;51Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1977 Dec 31;204(4):235-46Zlotogora J et al.AM J Med genetics 1990

Conclusion :

Bilateral corneal opacities with resulting photophobia causing her to keep

her eyes closed.In a setting of EDS/BCS- caused by minor trauma.

Treatment:Lubrication with which she was able to open her eyes for short

periods of time.Continued treatment with Cyclosporine LA/Flaxseed oil/Vitamin A Flash visual evoked potential showed normalP2 latencies with

reduced amplitudes

What is keeping her head flexed?Torticollis secondary to an unstable atlantoaxial

joint /atlanto-axial dislocation

Atlantoaxial instability: Case reports in Ehler Danlos syndrome Due to generalised laxity of ligaments

Awasthy N, Jnl of Pediatric neurosciences, 2008

Bhatia S J, J Assoc Physicians of India, 1990Philips WA, The cervical spine, 1998, 317-24Halko G.J, Jnl of Rheumatology, 1995

Treatment Cervical tractionAnalgesia

Able to keep her head upright immediately after completion of traction but returned to predominantly flexed position later.

Defenitive surgery

Neurological manifestationsThe bilateral cerebellar and cerebral atrophy

Neurological manifestation varied in Ehlers- Danlos

Cerebrovascular disease, peripheral neuropathy, Subependymal heterotopias, epilepsy Cerebellar atrophyAbnormal CT findings in patients with ED

Mathew et al Neurology India, Sept 2005Hagino H et al , Neuroradiology , Sept 1985