Christian Decock

Identification of 34 novel and 56 known FOXL2 mutations in patients with blepharophimosis syndrome

Blepharophimosis syndrome (BPES) is caused by loss‐of‐function mutations in the single‐exon forkhead transcription factor gene FOXL2 and by genomic rearrangements of the FOXL2 locus. Here, we focus on 92 new intragenic FOXL2 mutations, 34 of which are novel. Specifically, we found 10 nonsense mutations (11%), 13 missense mutations (14%), 40 deletions or insertions leading to a frameshift (43%), and 29 in‐frame changes (32%), of which 28 (30%) lead to a polyalanine expansion. This study confirms the existence of two previously described mutational hotspots. Moreover, we gained novel insights in genotype‐phenotype correlations, emphasizing the need to interpret genotype‐phenotype correlations individually and always in the context of further clinical observations.

Increased Levator Muscle Function by Supramaximal Resection in Patients With Blepharophimosis-Ptosis–Epicanthus Inversus Syndrome

OBJECTIVE To study the efficacy and clinical and anatomical results of supramaximal levator resection in patients with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) with severe congenital ptosis with poor levator function (LF). METHODS Eleven patients with molecularly proven BPES underwent supramaximal levator resection. Palpebral fissure height and LF were measured preoperatively and postoperatively. RESULTS All patients showed an excellent reduction in ptosis with a single intervention resulting in a clear visual axis. Palpebral fissure height improved from mean (SD) 3.3 (0.7) mm preoperatively to 7.1 (0.9) mm postoperatively (P value <.001). Four patients underwent additional surgery because of cosmetic issues with eyelid height asymmetry. All patients showed a marked, consistent, and lasting improvement in LF, going from mean (SD) 1.9 (0.9) mm preoperatively to 7.4 (1.1) mm postoperatively (P value <.001). This improvement could be attributed to the presence of a very long and thin tendon, as well as a striated muscle belly. This elongated aponeurosis inhibits the levator muscle from having sufficient impact on the vertical eyelid excursion. CONCLUSIONS We demonstrated that supramaximal levator resection performed in patients with BPES not only results in good cosmetic appearance in terms of ptosis reduction in the majority of cases but also in a significant increase of the levator palpebrae superioris function. An anatomical substrate was found to explain these findings. To our knowledge, this is the first study to provide evidence of a marked increase in LF in BPES due to resection of the elongated tendon with reinsertion of the muscle belly.

Occult orbito-cranial penetrating injury by pencil: role of beta tracer protein as a marker for cerebrospinal fluid leakage.

Orbito-cranial foreign bodies present a treacherous situation that can escape detection. The only evidence of these foreign bodies may be the entry wound in the form of a small lid laceration. A two-year-old boy presented with right upper lid laceration following a fall two hours back. Analysis of the fluid around the wound revealed a beta-tracer protein (beta-TP) value of 33.5 mg/l suggestive of cerebrospinal fluid (CSF). Three-dimensional computed tomography (CT) scan revealed a foreign body measuring 4.2 cm × 0.8 cm passing from the orbital roof to the frontal lobe. The foreign body tract was explored through the eyelid laceration and a broken pencil was removed followed by dural patch graft. The patient developed no ocular or intracranial complications. Beta-TP, a highly specific marker of CSF is routinely used in screening patients of neurosurgery and otolaryngology with CSF leaks, however, its use has never been reported in ophthalmic literature based on an online PubMed search.

Insights Into Levator Muscle Dysfunction in a Cohort of Patients With Molecularly Confirmed Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome Using High-Resolution Imaging, Anatomic Examination, and Histopathologic Examination

OBJECTIVE To study the basis of defective levator palpebrae superioris (LPS) function in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), an autosomal dominant eyelid malformation sometimes associated with ovarian dysfunction. METHODS Eight patients with molecularly proved BPES underwent high-resolution surface-coil 3-T magnetic resonance imaging before surgical intervention. The features of LPS muscle and adjoining connective tissue were compared with an age-matched control subject. During LPS resection for ptosis repair, detailed anatomic examination of the LPS was performed. Histopathologic characteristics were compared with normal control samples from a cadaver and a patient with simple severe congenital ptosis. RESULTS The most striking feature shown on magnetic resonance imaging was the thin, long anterior part of the LPS. During the operation, this consisted of a disorganized, thin, long aponeurosis. However, in the posterior part of the LPS, there was an organized thick structure suggestive of a muscle belly. Histopathologic examination revealed posteriorly well-formed striated muscle fibers in all patients with BPES but not in the control sample from the patient with simple severe congenital ptosis. These striated muscle fibers were comparable to those of the normal control tissue but were more intermixed with collagenous tissue and little fatty degeneration. CONCLUSIONS The presence of striated muscle fibers in LPS of patients with BPES contrasts with the fatty degeneration in patients with simple severe congenital ptosis. To our knowledge, this is the first study providing novel insights into the pathogenesis of the eyelid malformation in BPES through extensive imaging, anatomic study, and histopathologic testing in a unique cohort of patients with molecularly proved BPES.

Ectopic meningioma anterior to the lacrimal gland fossa

A 66-year-old man reported a slowly growing tumor on the lateral edge of his left upper eyelid. This lesion was hard but movable on palpation. A neoplasm of the lacrimal gland was suspected. CT showed a highly calcified lesion at the left upper eyelid. Resection of the tumor was performed, which was located just behind the orbital septum and in front of the lacrimal gland. Anatomopathologic investigation of the excised specimen with immunohistochemistry revealed a benign meningioma of a meningotheliomatous type, containing multiple bone elements. An ectopic orbital meningioma is rare, and this is the first case of a unique lateral localization of this lesion. Therefore, it should be included in the differential diagnosis of a lacrimal gland tumor.

Restrictive extraocular myopathy: a presenting feature of acromegaly

A 45-year-old man presented with binocular diplopia in primary gaze for 1 year. Orthoptic evaluation showed 10-prism diopter right eye hypotropia and 6-prism diopter right eye esotropia. The elevation and abduction of the right eye were mechanically restricted. This was associated with systemic features suggestive of acromegaly. Magnetic resonance imaging (MRI) of the brain demonstrated a pituitary macroadenoma. An elevated serum insulin-like growth factor I level and the failure of growth hormone suppression after an oral glucose load biochemically confirmed the diagnosis of acromegaly. Computed tomography (CT) of the orbit demonstrated bilateral symmetrical enlargement of the medial rectus and inferior rectus muscle bellies. All tests regarding Graves-Basedow disease were negative. Although rare, diplopia due to a restrictive extraocular myopathy could be the presenting symptom of acromegaly.

Ptosis as an associated finding in maternally inherited diabetes and deafness.

Purpose: To report ptosis as an associated finding in 2 patients with maternally inherited diabetes and deafness (MIDD). Methods: Two unrelated female patients with genetically proven MIDD are described. A complete ophthalmological examination included evaluation of levator muscle function, vertical fissure height and upper lid crease position measurements, the ice pack test and extensive imaging. In addition, pathology of the levator muscle was performed in 1 patient. Results: The first patient had an asymmetric ptosis at presentation. Levator muscle function was initially normal and decreased 3 years after, suggestive of a myogenic ptosis. Fundus examination revealed a macular pattern dystrophy. The second MIDD patient was referred for bilateral pigment alterations at the posterior pole. Gradually bilateral ptosis developed over a 3-year period. In both patients, ocular motility testing revealed a reduced upgaze. Conclusions: Myogenic ptosis has been described in association with several of the phenotypes caused by the m.3243A>G mutation, but up to now it had not been described as a finding in MIDD. MIDD has pleomorphic manifestations, and myogenic ptosis should be added to the list of associated clinical features. The additional symmetric elevation deficit in both patients may be an early sign of chronic progressive external ophthalmoplegia (CPEO). The results provide further evidence to suggest that MIDD represents only a part of a continuous spectrum of disease related to the m.3243A>G point mutation in the tRNALeu gene.

Inverted papilloma arising primarily from the lacrimal sac.

A 24-year-old female was referred with epiphora and a non-tender swelling within the right lacrimal fossa, present for 6 months. There were no previous episodes of dacryocystitis. Computed tomography showed a homogenous mass within the lacrimal fossa without contrast enhancement. Pathology following resection of the whole lacimal sac revealed the presence of an inverted papilloma (IP) with a sharp transition between the papilloma and the normal lacrimal duct epithelium. In situ hybridisation was positive for low risk HPV subtypes. An IP is a benign but infiltrative epithelial neoplasm with malignant potential characterised by a high recurrence rate. Majority of cases arise from the nasal wall and paranasal sinuses. In this case report, we demonstrate an IP confined to the lacrimal sac with clear-cut pathology proof, which implicates the lacrimal sac as a primary site of origin.

Extraskeletal osteosarcoma of the orbit: A clinicopathologic case report and review of literature

Primary extraskeletal osteosarcoma (EOS) is an extremely rare malignancy. In this report, the clinical course of a 32-year-old man presenting with proptoses is described. Medical history included Hirschsprung disease (HD), horseshoe kidney, azoospermia, and vertebral anomalies. Imaging of the orbit showed an oval, well-defined heterogeneous mass adjacent to the lateral wall of the orbit. The patient underwent a lateral orbitotomy and complete excision of the mass. The mass was not attached to the bone. Histopathologic and immunohistochemical examination confirmed the diagnosis of an EOS. The patient received chemotherapy and radiotherapy and is free of the disease 3 years after the diagnosis. Genetic screening showed no mutations for both the RET proto-oncogene for HD and the p53 tumor suppressor gene for osteosarcoma.

Orbital cellulitis as complication of endophthalmitis after cataract surgery

A 74-year-old man presented with light perception and presumed early bacterial endophthalmitis in the left eye after cataract surgery. Vitreous tap biopsy and core vitrectomy were performed immediately, along with injection of antibiotic agents (ceftazidime and vancomycin). Culture of the vitreous tap revealed Pseudomonas aeruginosa sensitive to ceftazidime. The eye remained inflamed despite 2 additional intravitreal ceftazidime injections. Orbital cellulitis with perforation of the globe was suspected and confirmed on magnetic resonance imaging, and enucleation was performed. Endophthalmitis due to P aeruginosa is associated with poor visual outcomes despite prompt treatment with appropriate intravitreal antibiotic agents. Progression to orbital cellulitis in immunocompetent patients is extremely rare. Careful monitoring of patients with endophthalmitis after cataract surgery is recommended. .