Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1.

BACKGROUND: Congenital fibrosis of the extraocular muscles types 1 and 3 (CFEOM1/CFEOM3) are autosomal dominant strabismus disorders that appear to result from maldevelopment of ocular nuclei and nerves. We previously reported that most individuals with CFEOM1 and rare individuals with CFEOM3 harbor heterozygous mutations in KIF21A. KIF21A encodes a kinesin motor involved in anterograde axonal transport, and the familial and de novo mutations reported to date predictably alter one of only a few KIF21A amino acids--three within the third coiled-coil region of the stalk and one in the distal motor domain, suggesting they result in altered KIF21A function. To further define the spectrum of KIF21A mutations in CFEOM we have now identified all CFEOM probands newly enrolled in our study and determined if they harbor mutations in KIF21A. RESULTS: Sixteen CFEOM1 and 29 CFEOM3 probands were studied. Three previously unreported de novo KIF21A mutations were identified in three CFEOM1 probands, all located in the same coiled-coil region of the stalk that contains all but one of the previously reported mutations. Eight additional CFEOM1 probands harbored three of the mutations previously reported in KIF21A; seven had one of the two most common mutations, while one harbored the mutation in the distal motor domain. No mutation was detected in 5 CFEOM1 or any CFEOM3 probands. CONCLUSION: Analysis of sixteen CFEOM1 probands revealed three novel KIF21A mutations and confirmed three reported mutations, bringing the total number of reported KIF21A mutations in CFEOM1 to 11 mutations among 70 mutation positive probands. All three new mutations alter amino acids in heptad repeats within the third coiled-coil region of the KIF21A stalk, further highlighting the importance of alterations in this domain in the etiology of CFEOM1.

Longitudinal correlation of thyroid-stimulating immunoglobulin with clinical activity of disease in thyroid-associated orbitopathy.

PURPOSE: To investigate the possible correlation between the changes in inflammatory active phase of thyroid-associated orbitopathy (TAO) with measured changes in thyroid-stimulating immunoglobulin (TSI) levels over time. This study was undertaken to evaluate the potential usefulness of measured TSI values in following and treating patients with TAO. METHODS: A retrospective chart analysis was performed on 23 patients who had been referred to a tertiary care oculoplastics service between July of 2002 and April of 2004 with suspected TAO. The activity status of patients with TAO was graded by using the TAO activity scale (TAOS), created to distinguish between the active and cicatricial phases of TAO. Laboratory values of TSI reported during the course of the study period were compiled for each study patient. RESULTS: Linear regression analysis revealed a statistical correlation between the changes in activity of TAO, as measured by the TAOS score, and changes in measured values of TSI over time. A statistically significant correlation was also found between the activity of TAO (measured by the TAOS score) and TSI value. CONCLUSIONS: It was found that changes in inflammatory phase of TAO, as measured by the TAOS score, statistically correlate with changes in measured TSI. An additional correlation was also found between the absolute score of TAO activity and measured level of TSI. These findings suggest that serial TSI measurements may be an adjunct in assessing clinical inflammatory activity of TAO and may help direct clinical decision making regarding treatment decisions in TAO.

Adverse reactions to permanent eyeliner tattoo.

PURPOSE: To report the potential for serious adverse reactions associated with permanent eyeliner tattoos. METHODS: An observational case series was conducted on 4 patients who presented with inflammatory eyelid reactions after receiving permanent eyeliner tattoo. RESULTS: Clinically, the tattoo-associated lesions were typically firm, raised masses underlying the areas of pigmentation. Histopathologic analysis of tissue from all 4 patients demonstrated a granulomatous inflammatory response with negative cultures for any organisms. Treatment approaches varied between a combination of topical steroid creams, local steroid injections, local resection, intramuscular steroid injection, and systemic oral steroids. These treatments were successful in all 4 cases. CONCLUSIONS: An allergic granulomatous reaction is one of the adverse reactions seen after permanent eyeliner tattoo. Treatment can be challenging and may ultimately require excision of tattoo pigment to remove the inciting factor. Systemic steroids may aid in controlling the inflammation associated with reaction to the tattoo pigment.

Orbital, middle cranial fossa, and pterygopalatine fossa yolk sac tumor in an infant.

A yolk sac tumor, also known as an endodermal sinus tumor, was diagnosed in a 15-month-old infant who presented with rapidly progressive right eye proptosis. Imaging of the orbits and brain revealed a mass in the right orbit, middle cranial fossa, and pterygopalatine fossa. A lateral orbitotomy was performed to take a biopsy specimen and to partially debulk the tumor secondary to signs of optic nerve compromise. The biopsy specimen revealed a yolk sac tumor, and the patient underwent systemic chemotherapeutic treatment. Because orbital endodermal sinus tumors have been infrequently reported, there are no firm prognostic or treatment guidelines. Our case demonstrates that early recognition, limited orbital debulking, and chemotherapy can have an excellent short-term outcome.