Explore the vast range of titles available.

Background/aimsMicrophthalmia, anophthalmia and coloboma (MAC) are clinically and genetically heterogenous rare developmental eye conditions, which contribute to a significant proportion of childhood blindness worldwide. Clear understanding of MAC aetiology and comorbidities is essential to providing patients with appropriate care. However, current management is unstandardised and molecular diagnostic rates remain low, particularly in those with unilateral presentation. To further understanding of clinical and genetic management of patients with MAC, we charted their real-world experience to ascertain optimal management pathways and yield from molecular analysis.MethodsA prospective cohort study of consecutive patients with MAC referred to the ocular genetics service at Moorfields Eye Hospital between 2017–2020.ResultsClinical analysis of 50 MAC patients (15 microphthalmia; 2 anophthalmia; 11 coloboma; and 22 mixed) from 44 unrelated families found 44% had additional ocular features (complex) and 34% had systemic involvement, most frequently intellectual/developmental delay (8/17). Molecular analysis of 39 families using targeted gene panels, whole genome sequencing and microarray comparative genomic hybridisation identified genetic causes in, 28% including novel variants in six known MAC genes (SOX2, KMT2D, MAB21L2, ALDH1A3, BCOR and FOXE3), and a molecular diagnostic rate of 33% for both bilateral and unilateral cohorts. New phenotypic associations were found for FOXE3 (bilateral sensorineural hearing loss) and MAB21L2 (unilateral microphthalmia).ConclusionThis study highlights the importance of thorough clinical and molecular phenotyping of MAC patients to provide appropriate multidisciplinary care. Routine genetic testing for both unilateral and bilateral cases in the clinic may increase diagnostic rates in the future, helping elucidate genotype–phenotype correlations and informing genetic counselling.

Congenital ocular anomalies significantly contribute to global disability, with 15–20% of infant blindness attributed to these anomalies. This study examined anophthalmia, microphthalmia, and coloboma (AMC) through collaborative neonatology and ophthalmology care. The global prevalence of AMC varies: anophthalmia at 0.6–4.2 per 100,000 births and microphthalmia at 2–17 per 100,000 births, with a combined prevalence of up to 30 per 100,000. The prevalence of coloboma, alone or associate with other eye defects is 2–19 per 100,000 live births. Anophthalmia and microphthalmia may present as isolated or genetic syndromes, necessitating comprehensive evaluation. AMC etiology encompasses genetic and environmental factors. Chromosomal aberrations and mutations in genes such as PAX6 , SOX2 , OTX2 , and CHD7 are contributors. Syndromic associations, such as CHARGE (heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness) syndrome, underscore the complexity of this syndrome. Early AMC diagnosis is pivotal for timely intervention. This work provides a literature review offering insights for effective management and genetic counseling in a pediatric context.

It is unclear whether siRNA-based agents can be a safe and effective therapy for diseases. In this study, we demonstrate that microphthalmia-associated transcription factor–siRNA (MITF-siR)-silenced MITF gene expression effectively induced a significant reduction in tyrosinase (TYR), tyrosinase-related protein 1, and melanocortin 1 receptor (MC1R) levels. The siRNAs caused obvious inhibition of melanin synthesis and melanoma cell apoptosis. Using a novel type of transdermal peptide, we developed the formulation of an MITF-siR cream. Results demonstrated that hyperpigmented facial lesions of siRNA-treated subjects were significantly lighter after 12 weeks of therapy than before treatment (P < 0.001); overall improvement was first noted after 4 weeks of siRNA treatment. At the end of treatment, clinical and colorimetric evaluations demonstrated a 90.4% lightening of the siRNA-treated lesions toward normal skin color. The relative melanin contents in the lesions and adjacent normal skin were decreased by 26% and 7.4%, respectively, after treatment with the MITF-siR formulation. Topical application of siRNA formulation significantly lightens brown facial hypermelanosis and lightens normal skin in Asian individuals. This treatment represents a safe and effective therapy for melasma, suggesting that siRNA-based agents could be developed for treating other diseases such as melanoma.

Non-coding RNAs provide additional regulatory layers to gene expression as well as the potential to being exploited as therapeutic tools. Non-coding RNA-based therapeutic approaches have been attempted in dominant diseases, however their use for treatment of genetic diseases caused by insufficient gene dosage is currently more challenging. SINEUPs are long antisense non-coding RNAs that up-regulate translation in mammalian cells in a gene-specific manner, although, so far evidence of SINEUP efficacy has only been demonstrated in in vitro systems. We now show that synthetic SINEUPs effectively and specifically increase protein levels of a gene of interest in vivo . We demonstrated that SINEUPs rescue haploinsufficient gene dosage in a medakafish model of a human disorder leading to amelioration of the disease phenotype. Our results demonstrate that SINEUPs act through mechanisms conserved among vertebrates and that SINEUP technology can be successfully applied in vivo as a new research and therapeutic tool for gene-specific up-regulation of endogenous functional proteins.

(1) Background: Oculo-facio-cardio-dental (OFCD) syndrome is a rare pathological condition with an X-linked dominant trait that only occurs in females; no males are born with OFCD syndrome. This syndrome is characterized by congenital cataracts with secondary glaucoma ocular defects, ventricular and atrial septal defects, or mitral valve prolapses. Facial traits are a long narrow face and a high nasal bridge with a bifid nasal tip. Dental anomalies include radiculomegaly, oligodontia, root dilacerations, malocclusion, and delayed eruption. (2) Methods: This clinical report describes a 26-year-old girl who suffers from OFCD syndrome and who was treated with a multidisciplinary approach. The treatment plan included orthodontic treatment, orthognathic surgery, namely LeFort I and a Bilateral Sagittal Split Osteotomy, and occlusal rehabilitation with implants. (3) Discussion: Early diagnosis and multidisciplinary treatment of orthodontic, orthognathic surgery and occlusal rehabilitation with implants make it possible to maintain tooth function and improve aesthetics with good prognoses for success. In this paper, we report a case of a female patient with OFCD syndrome, who was referred for orthodontic treatment and occlusal rehabilitation and treated with a multidisciplinary approach.

Congenital anophthalmia and microphthalmia are rare developmental defects of the globe. They often arise in conjunction with other ocular defects such as coloboma and orbital cyst. They may also be part of more generalised syndromes, such as CHARGE syndrome. Anophthalmia, microphthalmia, and coloboma are likely to be caused by disturbances of the morphogenetic pathway that controls eye development, either as a result of primary genetic defect, or external gestational factors, including infection or drugs that can influence the smooth processes of morphogenesis. The ophthalmologist is often the primary carer for children with anophthalmia and microphthalmia, and as such can coordinate the multidisciplinary input needed to offer optimal care for these individuals, including vision and family support services. They are able to assess the vision and maximise the visual potential of the child and they can also ensure that the cosmetic and social impact of anophthalmia or microphthalmia is minimised by starting socket expansion or referring to a specialist oculoplastics and prosthetics unit. A coordinated approach with paediatrics is necessary to manage any associated conditions. Genetic diagnosis and investigations can greatly assist in providing a diagnosis and informed genetic counselling.

Microphthalmia with linear skin defects syndrome (MIDAS) (MIM 309801) is a rare syndrome with an X-linked dominant transmission pattern, with male lethality.1 It is associated with deletions or unbalanced translocations in the short arm of X-chromosome (Xp22.3).2 Most cases are de novo, but familial recurrence has been described, with no clear genotype–phenotype correlations.3 The most consistent clinical features of MIDAS are microphthalmia and/or anophthalmia, sclerocornea and linear skin defects with dermal aplasia limited to face and neck, which were all present in this case and raised the clinical suspicion before the final diagnosis. Nervous system and cardiac anomalies, development delay, diaphragmatic hernia and genitourinary tract abnormalities, hearing loss and anal atresia with ectopic anus and fistula can also be present.1–3 The use of array CGH as the first laboratorial approach in the investigation of a newborn with a predicted diagnosis of MIDAS syndrome can confirm the diagnosis and may identify unsuspected copy number variants.3 The phenotype associated with the deletion found, can range from no clinical signs to in utero lethality, depending not only on somatic mosaicism, but also on cell selection mechanisms.3 The contribution of the duplication (Xp22.2p21.1) to the clinical manifestations here is unknown. Clinical spectrum of females with HCCS mutation: from no clinical signs to a neonatal lethal form of the microphthalmia with linear skin defects (MLS) syndrome.

Oculofaciocardiodental syndrome is a rare genetic disorder affecting ocular, facial, dental, and cardiac systems. The clinical diagnosis of oculofaciocardiodental syndrome can be challenging due to a wide variety of symptoms. Oculofaciocardiodental syndrome is found only in females due to its X-linked inheritance pattern and embryonic lethality for males. Radiculomegaly of canines is the most consistent finding in these patients. In this report we present a female patient with characteristic facial features, as well as a comprehensive overview of oculofaciocardiodental syndrome. Diagnosis of oculofaciocardiodental syndrome in this patient was verified by genetic analysis, during which we found a novel mutation in BCOR.

IntroductionCongenital anophthalmos and microphthalmos are reported to occur in 1–20/100 000 newborn infants. The conditions may be characterised by associated pathology in the fellow eye when unilateral disease is present and/or by complex systemic anomalies.MethodsWe conducted a review of 75 patients with congenital anophthalmos or blind microphthalmos who were examined in our department from 1997 to 2008. Data on pregnancy, birth and family history were collected. Patients were screened for any pathology in the fellow eye in unilateral disease and for any systemic anomaly.ResultsSixteen patients had blind unilateral microphthalmos. To date there has been only one case of bilateral microphthalmos. Congenital anophthalmos was unilateral in 38 and bilateral in 20 patients. Only one of the children had a positive family history for anophthalmos. None of the mothers had had problems in pregnancy or during delivery. There were more associated systemic findings in anophthalmic (50%) than in microphthalmic (17.6%) patients. Typically, the pathology was characterised by Goldenhar's syndrome, facial clefts and developmental cerebral anomalies. Four out of 16 patients with unilateral microphthalmos (25%) and 18 out of 38 patients with unilateral anophthalmos (47.4%) had anomalies in the fellow eye, predominantly coloboma, dermoid, sclerocornea and glaucoma. On account of this pathology in a single eye, two (12.5%) of the patients with unilateral microphthalmos and 13 (34.2%) of the patients with unilateral anophthalmos, as well as all 20 patients with bilateral anophthalmos, were classified as legally blind. Therefore the overall blindness rate was 17.6% in microphthalmos and 3.4 times higher (56.9%) in anophthalmos.ConclusionsAll children born with congenital anophthalmos or microphthalmos require a thorough clinical examination by an experienced ophthalmologist to rule out pathology in the fellow eye in unilateral disease and by a paediatrician to screen for any associated systemic anomalies.

Background/aim: Children with congenital microphthalmos are usually able to wear an eye prosthesis but the cosmetic aspect is determined by the size of the orbital volume deficiency. Instead of using a ball shaped standard hydrogel expander or a regular orbital implant, which would necessitate enucleation of the microphthalmic eye, this study investigates the feasibility of volume augmentation with injectable pellet expanders, as formerly suggested for acquired anophthalmos in adults only. Method: The pellet expander is made from a self inflating hydrogel that takes up water by osmosis (dry state: length 8 mm, diameter 2 mm, volume 0.025 ml; in vitro hydrated state after around 1 day: length 15 mm, diameter 4 mm, volume 0.24 ml; swelling capacity: 9.6-fold). This report concerns six patients (two girls and four boys) aged between 4 months and 42 months with unilateral microphthalmos who were treated by injection of 4–14 pellet expanders into the retrobulbar orbital tissue. Volume augmentation was 1–3.5 ml. The pellets were injected using a customised trocar and placed behind the microphthalmos directed into the intraconal space. Results: The increasing orbital volume was noticeable within 2 days and was confirmed by ultrasonography and magnetic resonance imaging. The final result can be anticipated by the volume augmentation effect produced by the amount of saline solution injected in the orbital apex region. All patients were fitted with an artificial eye, which was subsequently enlarged every 3–5 months. Anophthalmic enophthalmos was fully compensated with this technique. No complications have been encountered to date. Conclusions: Orbital volume augmentation with injectable self inflating hydrogel expander pellets is apparently a safe, quick, and minimally invasive technique for various indications in orbital reconstructive surgery—for example, to treat an enophthalmic appearance in microphthalmos and congenital or acquired anophthalmos.