Sphenoid sinus mucocele causing ptosis with pupil-spared ophthalmoplegia: a hint on carotid artery doppler ultrasound.

OBJECTIVE: Sphenoid sinuses mucocele (SSM) is an uncommon cause of orbital apex syndrome (OAS). Diagnosis of neurological complications in SSM might be delayed when the expansion of mucocele beyond the sinuses is not evident in conventional sinuses imaging. METHODS: We present a case of a 76-years old man with spared-pupil ophthalmoplegia associated with ptosis caused by a unilateral left SSM in which internal carotid artery Doppler ultrasound showed distal sub-occlusion waves pattern. RESULTS: Sinus occupation was noted in the magnetic resonance imaging (MRI) and was further evaluated in computed tomography (CT) scan and MR angiography. Nor CT or MR angiography showed clear evidence of neighboring structures compression. Doppler ultrasound of internal carotid showed high-resistance waveforms and decreased wave velocities helping diagnosis. Structures compression was confirmed intra-operatively and the patient was discharged asymptomatic after sphenoid sinus drainage. CONCLUSION: In this first report of carotid Doppler ultrasound findings in a patient with a neurological presentation of a sphenoid sinus mucocele, a high-resistance waveform of the internal carotid may help differentiate uncomplicated sinusitis from invasive mucocele.

Congenital Orbital Fibrosis With Spontaneous Regression of Orbital Tumor.

Congenital orbital fibrosis (COF) is a rare disorder characterized by an infiltrating orbital mass with secondary involvement of the extraocular muscles that may present with extraocular muscle dysfunction, and globe and eyelid abnormalities in infancy. This condition is thought to be a nonprogressive process and literature on longitudinal assessment of COF is limited. The authors describe a case of COF which was followed for 15 years. The patient had stable symptoms of ocular dysmotility and ptosis but was noted to have spontaneous regression of the orbital mass on serial MRI.

Congenital Conjunctival Cysts of the Orbit.

PURPOSE: To evaluate the clinical presentation, anatomical location, and histological features of congenital conjunctival cysts of the orbit. The location and the histological features of inflammation in these patients were compared with those for 293 orbital dermoid cysts. PATIENTS AND METHODS: Retrospective review of the clinical details, imaging, and histopathology for patients who had excision of conjunctival cysts from their orbit between 1992 and 2020; patients with a history of trauma or surgery were omitted. RESULTS: Twelve patients (7 male; 58%) with congenital conjunctival cysts were identified, the patients presenting at an average age of 16 years (median 26; range 1-61) with a symptoms for a mean duration of 20 months (median 24; range 6-36). The commonest symptoms were peribulbar lump (6/12 patients; 50%), and eyelid swelling and blepharoptosis (6/12 patients; 50%). An orbitaxl mass was palpable in 10 patients (83%), 3 patients (25%) had mild proptosis (1-3 mm), and the cysts were most commonly located superiorly (6/12 patients; 50%) or superonasally (3/12; 25%) in the anterior half of the orbit. Imaging was performed in 7 cases, this showing an intimate relation to the common sheath of the superior rectus/levator complex in 3 patients (25%) and to the trochlea in 1 (8%). All cysts were excised completely, and no patient had postoperative complications or recurrence. Chronic mild and nonspecific inflammation was evident within the cyst wall in 7 cases (54%), but-unlike 55% of the 293 dermoid cysts-none showed granuloma formation. CONCLUSION: Congenital conjunctival cysts are rare and usually present with a palpable mass in the upper eyelid sulcus. A significant proportion of these cysts have an intimate relationship with the trochlea, or the superior rectus, levator palpebrae or superior oblique muscles and, to minimize the risk of postoperative diplopia or ptosis, particular care must be exercised during surgery.

Elastoma of the Orbit: A Case Report.

A 78-year-old man presenting for revision ptosis surgery was found to have an asymptomatic left inferomedial orbital mass visible below the left lower eyelid on external inspection, and subconjunctivally on examination. This was subsequently diagnosed as an isolated elastoma. A mass in a similar location was excised 60 years previously. His other ophthalmological history included stable diplopia corrected with prism, left-sided ectropion, bilateral sequential phacoemulsification, and past bilateral ptosis which has been persistent on the left side despite surgical repair and revision. His examination revealed left hypertropia but was otherwise largely unremarkable. However, imaging demonstrated the soft tissue lesion abutting the left globe. An anterior orbitotomy was performed, and the lesion was biopsied and specimens sent for histopathological examination and immunohistochemistry. This is the first case of an elastoma of the orbit reported in the literature to the best of the authors' knowledge.

MASP1-related 3MC syndrome in a patient from Turkey.

3MC syndrome is a rare condition manifesting with typical facial appearance, postnatal growth deficiency, skeletal manifestations, and genitourinary tract anomalies. 3MC is caused by biallelic pathogenic variants in MASP1, COLEC11, or COLEC10. Here, we report an affected subject of Kurdish origin from Turkey presenting with facial dysmorphisms, such as, hypertelorism, blepharophimosis, blepharoptosis, highly arched eyebrows, umbilical hernia, and caudal appendage. These features were compatible with 3MC syndrome. Molecular analysis revealed a novel homozygous pathogenic variant, c.310C > T; p.Gln104Ter in the MASP1 gene, resulting in a premature stop codon. Few subjects with 3MC syndrome have been reported in the literature so far. Thus, detailed study of this subject contributes to the evolving clinical and genetic characterization of 3MC syndrome.

CHARGE syndrome without colobomas: Ophthalmic findings.

To report ophthalmic findings of patients without colobomas, and with a clinical and molecular diagnosis of CHARGE Syndrome. Retrospective study of ophthalmic findings in 67 CHARGE patients-clinically confirmed diagnosis with positive CHD7 mutation-seen in the Ophthalmology department of Cincinnati Children's Hospital Medical Center between January 1, 2008 through September 25, 2018. Criteria for inclusion in this study was absence of any form of a coloboma in either eye. In our cohort, all patients had a positive CHD7 mutation, in addition to a clinical diagnosis. 19.4% (13/67) of CHARGE patients did not have a coloboma in either eye. 69.2% (9/13) had strabismus, 76.9% (10/13) had a refractive error that warranted refractive correction, 23.1% (3/13) had amblyopia, 38.5% (5/13) had nasolacrimal duct obstruction, 30.8% (4/13) had dry eye syndrome and exposure keratopathy, 15.4% (2/13) had ptosis, 15.4% (2/13) had blepharitis, 15.4% (2/13) had Cortical Visual Impairment, 7.7% (1/13) of patients had optic nerve drusen, 7.7% (1/13) had Marcus Gunn Jaw Winking, and 7.7% (1/13) with an eyelid nevus. There are numerous ophthalmic findings in individuals with CHARGE Syndrome without colobomas. No study to date has evaluated the ophthalmic findings in CHD7 positive CHARGE patients without colobomas. These findings need to be assessed and treated to ensure optimal vision in the CHARGE patient population. Absence of coloboma does not rule out a diagnosis of CHARGE syndrome, and if there is a clinical suspicion, clinical confirmation then genetic testing would be warranted.

A new 1p36.13-1p36.12 microdeletion syndrome characterized by learning disability, behavioral abnormalities, and ptosis.

Two 1p36 contiguous gene deletion syndromes are known so far: the terminal 1p36 deletion syndrome and a 1p36 deletion syndrome with a critical region located more proximal at 1p36.23-1p36.22. We present even more proximally located overlapping deletions from seven individuals, with the smallest region of overlap comprising 1 Mb at 1p36.13-1p36.12 (chr1:19077793-20081292 (GRCh37/hg19)) defining a new contiguous gene deletion syndrome. The characteristic features of this new syndrome are learning disability or mild intellectual disability, speech delay, behavioral abnormalities, and ptosis. The genes UBR4 and CAPZB are considered the most likely candidate genes for the features of this new syndrome.

Sacral protuberance with cleft lip and palate: Prenatal presentation of 3MC syndrome.

3MC syndromes are rare heterogeneous autosomal recessive conditions previously designated as Mingarelli, Malpuech, Michels, and Carnevale syndromes, characterized by dysmorphic facial features, facial clefts, growth restriction, and intellectual disability. 3MC is secondary to mutations in the MASP1, MASP3, COLEC11, and COLEC10 genes. The number of patients with 3MC syndrome with known mutations in the COLEC11 or MASP1 is, to date, less than 50. At the time this case presented (2015), the only gene identified in Online Mendelian Inheritance in Man to be associated with 3MC syndrome was MASP1. We present, to the best of our knowledge, the first prenatal report of 3MC syndrome, secondary to a homozygous variant in MASP1. Fetal findings included bilateral cleft lip and palate, abnormality of the sacral spine, a right echogenic pelvic kidney, and brachycephaly. 3MC syndrome should be considered as part of the differential diagnosis when fetal ultrasound detects facial clefts and spinal defects, as the risk of recurrence is significant and a molecularly confirmed diagnosis allows for alternate reproductive options.

[Clinical histopathologic characteristics of lacrimal glands in lacrimal gland prolapse with blepharochalasis].

Objective: To analyze the clinical histopathologic characteristics of lacrimal glands and possible mechanisms of lacrimal gland prolapse in blepharochalasis (BC). Methods: A case-controlled study of 23 consecutive patients with prolapse of lacrimal glands in BC was performed. All samples were obtained during surgery from the Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University between January 2009 and December 2016. The lacrimal tissue included prolapsed lacrimal glands (30 samples) and controls from the donors in the eye bank of Beijing Tongren Hospital, Capital Medical University (8 samples). Hematoxylin-eosin staining, special staining, immunohistochemistry and colloidal gold-labeled pre-embedded indirect immunogold electron microscopy (Gold-IIEM) were performed to analyze the histopathologic characteristics of the samples. The nonparametric Wilcoxon signed-ranks test was carried out for statistical analysis. Results: Among the 23 patients with lacrimal gland prolapse in BC, there were 3 males and 20 females. The mean age of morbidity was 11 years old (7-16 years). In the 8 normal control cases, 3 males and 5 females were included. The mean age was 15 years (10-20 years). In the 30 prolapsed lacrimal gland samples, hematoxylin-eosin staining showed enlargement of glandular lumina accompanied by inflammatory infiltrates of interstitial tissue in 2 samples. Marked loosening of collagen fibers of the obtainable lacrimal fascia was observed. The results on immunohistochemical staining demonstrated an increased level of immunocytes in the 30 prolapsed lacrimal gland samples, including IgA (+++, ++, +, -; 12, 11, 4, 3 vs. 0, 0, 1, 7; Z=-3.892), CD3(+)T cells (+++, ++, +, -; 2, 19, 7, 2 vs. 0, 0, 1, 7; Z=-4.168), matrix metalloproteinase (MMP)-3 (+++, ++, +, -; 0, 0, 11, 19 vs. 0, 0, 0, 8; Z=-2.005) and MMP-9 (+++, ++, +, -; 14, 14, 0, 2 vs. 0, 0, 0, 8; Z=-4.552) (all P<0.05). IgG, IgM, CD20 and C1-inhibitor were either absent or expressed at background level in the 30 prolapsed lacrimal gland samples (all P>0.05). Gold-IIEM showed zymogon granules in lacrimal glands were out of shape. MMP-3 and MMP-9 colloidal gold particles existed on the zymogon granules, and MMP-3 colloidal gold particles also existed on the surface of lacrimal gland epithelial cells. Conclusions: The histopathological changes in the lacrimal glands of lacrimal gland prolapse with BC include inflammatory infiltration, elastic fiber degeneration, marked loosening of the supporting fascia tissue, and an increased level of immunocytes, including IgA, CD3(+)T cells, MMP-3 and MMP-9. The results suggest that lacrimal gland prolapse with BC may result in the immuno-pathogenetic mechanisms with the involvement of cell-mediated immune responses. (Chin J Ophthalmol, 2020, 56: 205-210).

A TUBB6 mutation is associated with autosomal dominant non-progressive congenital facial palsy, bilateral ptosis and velopharyngeal dysfunction.

Congenital cranial dysinnervation disorders (CCDDs) comprise a heterogeneous spectrum of diseases characterized by congenital, non-progressive impairment of eye, eyelid and/or facial movements including Möbius syndrome, Duane retraction syndrome, congenital ptosis, and congenital fibrosis of the extraocular muscles. Over the last 20 years, several CCDDs have been identified as neurodevelopmental disorders that are caused by mutations of genes involved in brain and cranial nerve development, e.g. KIF21A and TUBB3 that each plays a pivotal role for microtubule function. In a five-generation pedigree, we identified a heterozygous mutation of TUBB6, a gene encoding a class V tubulin which has not been linked to a human hereditary disease so far. The missense mutation (p.Phe394Ser) affects an amino acid residue highly conserved in evolution, and co-segregates with a phenotype characterized by congenital non-progressive bilateral facial palsy and congenital velopharyngeal dysfunction presenting with varying degrees of hypomimia, rhinophonia, impaired gag reflex and bilateral ptosis. Expression of the mutated protein in yeast led to an impaired viability compared to wildtype cells when exposed to the microtubule-poison benomyl. Our findings enlarge the spectrum of tubulinopathies and emphasize that mutations of TUBB6 should be considered in patients with congenital non-progressive facial palsy. Further studies are needed to verify whether this phenotype is indeed part of the CCDD spectrum.

Orbital Septum Fibrosis in Congenital Ptosis Correlates With Eyelid Function: A Clinicopathologic Study.

PURPOSE: Congenital ptosis can threaten visual function and is usually treated with surgical correction. This study tests the hypothesis that congenital ptosis involves not only the levator muscle but also the orbital septum, which may tether the eyelid in the primary position. METHODS: A retrospective chart review was performed on 30 patients (41 eyelids) with congenital ptosis who underwent surgical correction that included partial septum excision. Histologic analysis was performed by a masked pediatric pathologist, with grading of septal tissue disorganization and fibrosis based on standard histologic criteria. An independent comparison of histologic grading with clinical ptosis measures was then performed. RESULTS: Fifteen eyelids demonstrated significant septal fibrosis, 19 were mild, and 7 were not fibrotic. Thirty-six eyelids demonstrated histologic disorganization. Mildly fibrotic eyelids were found to have reduced preoperative levator function than those that were not fibrotic (2.84 ± 1.92 vs. 9.57 ± 4.76 mm; p < 0.0001). Samples that demonstrated significant fibrosis were also found to have reduced preoperative levator function (4.67 ± 2.12 vs. 9.57 ± 4.76 mm; p = 0.0007). Histologically disorganized samples were also found to have a lower preoperative levator function (9.50 ± 6.04 vs. 3.99 ± 2.49; p = 0.0052). CONCLUSIONS: Orbital septae in patients with congenital ptosis demonstrate histologic disorganization and fibrosis. When decreased levator function is observed clinically, septal fibrosis and/or disorganization is likely present. These observations suggest that debulking the fibrotic septum during congenital ptosis surgery may improve outcomes by releasing the eyelid from its congenitally tethered position, improving eyelid elasticity.

Surgical Predictors of Reduced Marginal Reflex Distance After Upper Blepharoplasty.

PURPOSE: Ptosis may occur in certain cases after upper blepharoplasty. The authors aim to characterize the incidence of postoperative marginal reflex distance (MRD1) reduction after upper blepharoplasty and surgical variables that may predict this occurrence. METHODS: In this cross-sectional study, patients > 18 years old undergoing upper blepharoplasty were screened. Patients were excluded if they had any history of ptosis and brow surgery. Data regarding the excision of skin, muscle, fat, and brow fat as well as crease formation were documented. The distance in millimeter from the center of the pupil to the upper eyelid margin in the midpupillary line (MRD1) was measured digitally. The primary outcome measure was a postoperative reduction in MRD1 of >1 mm. Secondary outcome was overall mean change in MRD1 and the incidence of ptosis as defined by a final MRD1 ≤ 2.5 mm. RESULTS: The final sample consisted of 100 patients (200 eyelids) and the mean age was 55.8 years. There were 65 patients with orbicularis muscle removal, 52 patients with postseptal fat removed, and 9 patients with crease formation. Overall 15 patients developed MRD1 decrease of greater than 1 mm (5 bilaterally and 10 unilaterally) with 7 eyes demonstrating a final MRD1 of ≤ 2.5 mm. In multivariate modeling, muscle removal was found to be the only variable with significant impact on the development of MRD1 reduction > 1 mm after upper blepharoplasty (p < 0.05, odds ratio = 8.2). The other variables did not significantly contribute. The overall mean (SD) MRD1 was 3.43 mm (1.1) preoperatively and 3.62 mm (1.1) postoperatively (p < 0.01). CONCLUSIONS: Fifteen percent of patients demonstrated a reduction in MRD1 > 1 mm after upper eyelid blepharoplasty, and those with orbicularis resection were more likely to experience this change.The authors' study demonstrates a 15% incidence of postoperative MRD1 reduction after upper eyelid blepharoplasty. Orbicularis oculi muscle removal was significantly associated with this occurrence.

Primary Lash Ptosis.

INTRODUCTION: Lash ptosis is often an overlooked sign that may coexist with congenital and acquired blepharoptosis. This is a report of case series of patients presented in an oculoplastic clinic with visual field loss associated with lash ptosis. On examination, the primary pathology was attributed to lash ptosis dehiscence. METHODS: All patients underwent anterior lamellar repositioning and were followed for an average of 15 (10-24) months. RESULTS: All patients had resolution of visual field loss and heaviness of eyelids. CONCLUSIONS: Lash ptosis is associated with abnormalities such as floppy eyelid syndrome. However it may be a primary condition, with no background eyelid pathology and no external explanation for the eyelash ptosis. The condition might result from anatomical changes in the orbicularis oculi, Riolan's muscle, and tarsal plate. Patients in this series complained of upper lid visual field restriction. Anterior lamellar repositioning resulted in complete resolution of complaints. Additional studies are needed to learn about the pathophysiology of this entity.

Significance of Early Postoperative Eyelid Position on Late Postoperative Result in Mueller's Muscle Conjunctival Resection and External Levator Advancement Surgery.

PURPOSE: The purpose of this study was to determine whether advancement of the levator aponeurosis in external levator resection surgery or Mueller's muscle and conjunctiva in Mueller's muscle conjunctival resection (MMCR) surgery has a differential effect on variation in eyelid position during the postoperative period. METHODS: In this retrospective observational cohort study, 2 groups of patients were defined. The first underwent MMCR surgery without tarsectomy by surgeon 1. The second underwent external levator resection without dissection posterior to the levator aponeurosis by surgeon 2. Marginal reflex distance (MRD1) was calculated based on digital photographs at baseline, 1 week postoperatively and at 3-month follow up. The primary outcome measure was change in MRD1 over time. The secondary outcome was defined as the proportion of patients with minimal early postoperative change (change of MRD1 less than 0.5 mm at 1 week postoperatively). Repeated measures analysis of variance, t test, and chi-square analyses were performed. RESULTS: Of the 114 eyes in the sample, there were 68 in the MMCR group and 46 in the external levator resection group. A significant interaction between group and time was noted (p < 0.05), indicating change in MRD1 over time was different between the groups. Bonferroni corrected multiple comparisons yielded significant differences between each time point for MMCR surgery (p < 0.01). No difference in MRD1 was noted for the external levator resection group from the early to late postoperative visit. Comparing each time point across groups revealed significantly lower MRD1 for the MMCR group at the early postoperative visit (p < 0.01). Preoperative and late postoperative MRD1 did not significantly differ between the groups. Regarding the secondary outcome, patients undergoing MMCR surgery were 3.7× as likely to demonstrate <0.5 mm of change in MRD1 at week 1 (p < 0.05). When considering the 39.7% (n = 27) MMCR patients in this category, 59.3% (n = 16) went on to show an MRD1 increase >1 mm from the early postoperative to the late postoperative time points. CONCLUSIONS: Both external levator resection and MMCR can effectively elevate the eyelid in cases of primary involutional ptosis, and have similar late postoperative results. The authors found that MMCR cases undergo greater change between the early and late postoperative period, suggesting the process of eyelid elevation after MMCR may be dynamic, involving postoperative physiologic modification.

[Pathological features of levator aponeurosis in patients with involutional blepharoptosis].

Objective: To observe pathological features of levator aponeurosis in patients with involutional ptosis. Methods: A prospective study. Twenty-nine consecutive patients with involutional blepharoptosis who underwent levator aponeurosis advancement surgery for blepharoptosis correction were enrolled at Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University from 2007 to 2013. Twenty-nine specimens of the levator aponeurosis were obtained during surgery. Hematoxylin-eosin staining, Van Gieson staining, Masson staining, immunohistochemistry and transmission electron microscope observations were performed to observe the features of levator aponeurosis. Twelve normal specimens of fresh levator aponeurosis were obtained from Beijign Tongren Eyebank as control group. Mann-Whitney's U-test and multiple linear regression were used for statistical analysis. Results: Among the enrolled cases, there were 19 males and 10 females;14 cases were diagnosed with moderate ptosis and 15 cases with severe ptosis;9 cases involved with both eyes, 9 cases with right eyes, and 11 cases with left eyes. The mean age was 59 years. Among the 12 normal cases, there were 5 males and 7 females. The mean age was 56 years. Histopathological observation showed fascicle disruption(+++, ++, + 24, 2, 3 vs. 0, Z=-5.666, P<0.001), scarcity of cross-striations(+++, ++, + 23, 2, 4 vs. 0, Z=-5.582,P<0.001), collagen fibers hyperplasia(+++, ++, + 15, 10, 4 vs. 0, Z=-5.223,P<0.001), fatty infiltration(+++, ++, + 24, 5, 0 vs. 0, Z=-5.671,P<0.001), and a decrease of myoglobin expression(+++,++,+,- 9, 1, 1, 15 vs. 8, 1, 0, 0, Z=-3.004, P=0.005) in levator aponeurosis. Transmission electron microscope recorded presence of collagen fiber hyperplasia and cellular degeneration including mitochondria swelling and hyperplasia, vacuoles, lipid droplets, nucleus pycnosis, chromosome condensation, disintegrated organelles, myeloid body and autophagy. Multivariate linear regression showed a correlation between fat infiltration and age(ß=0.425, P=0.043) while suspicious related clinical features as independent variables and observed histopathological features as dependent variables. Conclusion: The levator aponeurosis appears to be involved with muscle fiber degeneration, collagen fiber hyperplasia and cellular degeneration in patients with involutional blepharoptosis. (Chin J Ophthalmol, 2018, 54: 671-677).

Peripheral T-Cell Lymphoma Presenting as a Primary Uterine Cervix Mass: A Report of a Rare Case.

Malignant lymphoma is a rare form of malignancy in the uterine cervix. Most of the previously reported cases were B-cell lymphomas. We present a case of primary peripheral T-cell lymphoma, not otherwise specified, in the uterine cervix in a 49-year-old woman with a history of severe vaginal bleeding. The patient was treated with a CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) chemotherapy regimen and 28 cycles of radiotherapy. Three months later, she presented with generalized lymphadenopathy and sudden left-eye ptosis as a complication of CNS involvement and died after 20 months from the initial disease presentation.

Alternating ptosis associated with asialo-GM1 and GD1b antibodies.

Miller Fisher syndrome (MFS), variant of acute inflammatory demyelinating polyradiculoneuropathy, is recognized as clinical triad (ophthalmoplegia-ataxia-areflexia). Ganglioside antibodies play an important role in the pathogenesis of acute polyradiculoneuropathy including MFS. To our knowledge, there has been no report of MFS presenting with atypical alternating ptosis or with concurrent elevation of serum GD1 and asialo-GM1 antibody titers, and negative titers of GQ1b antibody such as our patient. Our objective is to report MFS with unusual symptoms and to share our diagnostic approach. We report a rare case of MFS presenting with alternating eyelid ptosis, paresthesia, and ataxia after a respiratory infection. Initial neurological examination revealed left eyelid ptosis, hyporeflexia, positive Romberg sign, and ataxia. The ice pack test was negative. Three days later, contralateral ptosis was observed, associated with areflexia and worsened ataxia. However, there was significant improvement of the previous left eyelid ptosis. Serology revealed elevated asialo-GM1 and GD1b antibodies. Acetylcholine receptor antibodies were negative. Cerebral spinal fluid revealed elevated IgG index. Nerve conduction studies (NCS) performed four days after the onset of symptoms showed normal nerve conduction velocities and F-waves, and absent bilateral H-reflexes. Repetitive nerve stimulation (3 Hz) showed no decrement of compound muscle action potentials. Trial with a single dose of pyridostigmine showed no clinical improvement. The symptoms resolved without intervention. NCS 18 days after onset of symptoms showed mildly prolonged F-waves and absent H-reflexes. This case highlights an atypical presentation of MFS and raises the awareness of a rare autoantibody associated with it.

Two Cases of Conjunctival Amyloidosis Found as Ptosis.

Background: Amyloidosis is a spectrum of disorders characterized by the deposition of amyloid that causes severe damage to many organ systems. However, conjunctival amyloidosis is thought to be the manifestation of a local immunologic disorder and rarely affects the organ systems. We present two cases of conjunctival amyloidosis found as unilateral ptosis at initial visit. Case 1: 43-year-old-woman presented with unilateral ptosis and discomfort for the left eye. She had been treated with topical antihistamines and corticosteroids for allergic conjunctivitis. However, as symptoms persisted she was referred to us. At initial visit, unilateral ptosis, subconjunctival hemorrhage and waxy-yellow mass were found. Incisional biopsy was performed and histpathological examination revealed amyloid in the conjunctival stroma. Case 2: 31-year-old woman presented with unilateral ptosis and discomfort of palpebral superior conjunctiva in the left eye. At initial visit, the examination of the left superior palpebral conjunctiva showed waxy-yellow mass and hemorrhage. Incisional biopsy was performed and histopathological examination revealed amyloid in the conjunctival stroma. Conclusion: Unilateral ptosis may be an indication of conjunctival amyloidosis.

Improved locus-specific database for OPA1 mutations allows inclusion of advanced clinical data.

Autosomal-dominant optic atrophy (ADOA) is the most common inherited optic neuropathy, due to mutations in the optic atrophy 1 gene (OPA1) in about 60%-80% of cases. At present, the clinical heterogeneity of patients carrying OPA1 variants renders genotype-phenotype correlations difficulty. Since 2005, when we published the first locus-specific database (LSDB) dedicated to OPA1, a large amount of new clinical and genetic knowledge has emerged, prompting us to update this database. We have used the Leiden Open-Source Variation Database to develop a clinico-biological database, aiming to add clinical phenotypes related to OPA1 variants. As a first step, we validated this new database by registering several patients previously reported in the literature, as well as new patients from our own institution. Contributors may now make online submissions of clinical and molecular descriptions of phenotypes due to OPA1 variants, including detailed ophthalmological and neurological data, with due respect to patient anonymity. The updated OPA1 LSDB (http://opa1.mitodyn.org/) should prove useful for molecular diagnoses, large-scale variant statistics, and genotype-phenotype correlations in ADOA studies.

Beyond Ohdo syndrome: A familial missense mutation broadens the MED12 spectrum.

Intellectual disability (ID) is estimated to affect 1-3% of the general population and is a common reason for referrals to pediatric and adult geneticists, as well as neurologists. There are many genetic and non-genetic causes of ID; X-linked forms are identifiable through their characteristic inheritance pattern. Current testing methods have been able to identify over 100 genes on the X chromosome responsible for X-linked intellectual disability (XLID) syndromes. MED12 [MIM *300188] (mediator complex subunit 12) mutations have been linked to numerous XLID syndromes, including Lujan, FG, and Ohdo, and MED12 is included in many XLID panels. MED12 is located at Xq13.1 and its product has roles in transcriptional activation and repression. We describe two affected male siblings and their unaffected mother with a novel missense mutation in MED12, c.4147G>A (p.Ala1383Thr). The siblings share some features of Ohdo syndrome, including feeding difficulties, microcephaly, and speech delay. However, additional attributes such as hypertonia, eosinophilic esophagitis, penile chordee, and particular facial dysmorphisms depart sufficiently from individuals previously described such that they appear to represent a new and expanded phenotype. This case lends credence to the evolving theory that the subtypes of Ohdo, and perhaps other MED12 disorders, reflect a spectrum of characteristics, rather than distinct syndromes. As XLID panel testing and whole exome sequencing (WES) becomes a standard of care for affected males, further MED12 mutations will broaden the phenotype of these intriguing disorders and challenge clinicians to rethink the current diagnostic boundaries.