Grand Rounds Conference

Janelle Fassbender, MD, PhDUniversity of Louisville

Department of Ophthalmology and Visual Sciences

February 21, 2014

SubjectiveCC: Rubbing eyes a lot and sensitive

to sunlight

HPI: 3 year old boy presents with light sensitivity and squinting since birth per mother.

History

POH: NonePMH: Noonan syndromeEye Meds: Artificial tearsMeds: Zyrtec prnAllergies: NKDAFOH: Glaucoma (Grandmother)

Objective

OD OSVA: CSM CSMCRx: -0.5 + 0.75 x 090 -0.5 +

0.75 x 090Pupils: 4 to 2 mm OU, no RAPDIOP: Soft SoftEOM: Full Full

ObjectiveSLE: External Low set ears, webbed neckLids Fine cilia arising from meibomian glands all 4 eyelidsConjunctiva/Sclera Normal OUCornea Clear OUAnterior Chamber Deep, quiet OUIris Normal OULens Clear OUVitreous Normal OU

Clinical Photographs

Low-set ears Short, webbed neck

Mock clinical photo

Patil et al, 2004

Differential Diagnosis Distichiasis

Congenital Acquired

Trichiasis

Assessment

3 year old boy with symptomatic, congenital distichiasis.

Operation

Initial procedure: Bilateral upper lid lash margin rotation with mucous membrane grafts (MMG).

Follow up procedure for lower eyelids.

Operation Report

Incision elongated across the horizontal extent of the posterior side of the gray line.

The anterior lamellae of the eyelid was advanced to the superior margin of the tarsus and secured.

Thin block of tarsus excised to remove lash follicles.

Full-thickness buccal mucous membrane graft placed on the eyelid margin and sutured.

Follow-up Upper lid procedure follow-up

Post-op month 2 – Grafts healing well, new cilia arising through grafts

Procedure #2 2/13/14 – MMG bilateral lower lid

Congenital distichiasis

Accessory cilia arise from meibomian gland orifices

Second month of gestation, cilia and meibomian glands differentiate. Congenital distichiasis specialized sebaceous

gland improperly differentiates into pilosebaceous unit

Acquired distichiasis Chronic irritation/inflammation

Patients may become symptomatic early in life Hairs are fine, lanugo-like, and curl away from

the globe

Lymphedema-distichiasis syndrome

First described in 1899 by Kuhnt Distichiasis with lower limb lymphedema

Autosomal dominant, mutation of FOXC2, chromosome 16q24.3

Abnormal interaction between the lymphatic endothelial cells and pericytes, as well as valve defects (Petrova et al, 2004)

Ptosis (31%), congenital heart defects (6.8%), cleft palate (4%) (Brice et al, 2002)

94.6% have distichiasis 6 patients were under 11 yrs old and had not

developed lymphedema (Brice et al, 2002) 50% males symptomatic by age 11 50% females symptomatic by age 20

Treatment of Distichiasis Lubricants and soft contacts Electrolysis, radiofrequency epilation or

cryoepilation Surgical options:

Lid splitting and posterior lamella cryosurgery (Anderson et al, 1981)

Eyelid splitting with excision (Vaughn et al, 1997) Tarsal resection and mucous membrane

grafting (White et al, 1975)

High rate of recurrence

Noonan Syndrome Prevalence: 1:1000 to 1:2500 live births Mutations in genes of the RAS/MAPK signaling

pathway PTPN11 mutations (chromosome 12q24.1) – 50%

patients Characteristic facies:

Low-set ears, malar flattening, low hairline Systemic manifestations:

Malignancy – hematologic, rhabdomyosarcoma, giant cell granulomas

Cardiac defects, short stature, hearing loss

Noonan Syndrome continued

Orbital manifestations: Downward-sloping palpebral fissures (38-74%),

hypertelorism (57-74%), ptosis (48-51%), epicanthal folds (39%)

Refractive error (61%), strabismus (48%), amblyopia (33%), anterior segment changes (57-63%), abnormal fundoscopy (8-20%)

Lymphedema-distichiasis masquerade? Pterygium colli as a feature of 10 individuals from

5 generations (Falls and Kertesz, 1964) 2 females considered to have Turner syndrome,

found to have distichiasis with peripubertal onset lymphedema (Toro et al, 1991)

Example

References Dagenais SL, et al. 2004. FOXC2 is expressed in developing

lymphatic vessels and other tissues associated with lymphedema-distichiasis syndrome. Gene Expression Patterns, 4: 611-19.

Sola P, et al. 1991. Distichiasis-lymphedema syndrome and the Turner phenotype. Medical association of Puerto Rico Bulletin, 83(12): 543-544.

Randolph JR, et al. 2011. Orbital manifestations of Noonan Syndrome. Ophthal Plast Reconstr Surg, 27(6): e160-163.

Fang, J, et al. 2000. Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. Am J Hum Genet, 67:1382–8.

Brice G, et al. 2002. Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24. J Med Genet, 39:478–83.

Patil BB, et al. 2004. Distichiasis without lymphoedema. Eye, 18:1270-1272.

Falls and Kertesz. 1964. A new syndrome combining pterygium colli with developmental abnormalities of the eyelids and lymphatics of the lower extremities. Trans Am Ophthalmol Soc, 62:248-272.