It encompasses all individuals with a SOX2 pathogenic variant who should be evaluated for medically actionable manifestations across the entire phenotypic spectrum (regardless of clinical findings that prompted molecular genetic testing). Ocular features almost identical to those frequently observed in, Brain features almost identical to those of, Esophageal atresia/tracheo-esophageal fistula & dystonia are not assoc w/, Bilateral microphthalmia &/or coloboma, iris hypoplasia, cataract, lens subluxation. SOX2 anophthalmia syndrome is estimated to affect 1 in 250,000 individuals. Guichet A, Triau S, Lepinard C, Esculapavit C, Biquard F, Descamps P, Encha-Razavi F, Bonneau D. Prenatal diagnosis of primary anophthalmia with a 3q27 interstitial deletion involving SOX2. As the lung develops, cells become specified and differentiate into the various cell lineages. Always go to your appointments, even if you feel fine. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. SOX2 is expressed in mouse embryonic stem cells and has been shown to act as part of a transcriptional activator complex for several important developmental genes including other genes known to be critical to eye development (e.g., PAX6 and MAF1). GeneReviews staff have not independently verified the classification of variants. The SOX2 protein regulates the activity of other genes, especially those that are important for normal development of the eyes. While both eyes are usually affected in SOX2 anophthalmia syndrome, one eye may be more affected than the other. Researchers dont know for sure what causes anophthalmia or what causes microphthalmia. Less frequent variants, esp those that alter residues adjacent to Tyr160, are also assoc w/severe phenotype. Most cases result from new mutations in the SOX2 gene and occur in people with no history of the disorder in their family. Introduction. Novel mutations in PAX6, OTX2 and NDP in anophthalmia, microphthalmia and coloboma. Epub 2007 May 2006 Jun 15;15(12):2030. usta tennis court construction specifications / why is rebecca lowe hosting olympics / sox2 anophthalmia syndrome life expectancy. the diversifying clinical signs. Anophthalmia and microphthalmia may also be part of congenital syndromes, including: You may feel concerned if youre pregnant and you find out that your child may have microphthalmia or anophthalmia. Individuals with SOX2 anophthalmia syndrome may also have seizures, brain abnormalities, slow growth, delayed development of motor skills (such as walking), and mild to severe learning disabilities. Your provider may suggest genetic testing before you get pregnant after discussing your medical history and your family history. AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; ID = intellectual disability; MCOPS5 = microphthalmia, syndromic 5; MOI = mode of inheritance; XL = X-linked, Reis et al [2011]; Author, unpublished data, Deml et al [2016], Williamson et al [2020], ADL = activities of daily living; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance; OT = occupational therapy/therapist; PT = physical therapy/therapist, Medical geneticist, certified genetic counselor, or certified advanced genetic nurse, ASM = anti-seizure medication; DD = developmental delay; ID = intellectual disability; OT = occupational therapy; PT = physical therapy. HGNC; In bilateral anophthalmia, both eyes are missing. People can be born with one or two small eyes (microphthalmia) or without one or both eyes (anophthalmia). Developmental Disabilities Administration (DDA) enrollment is recommended. 8 color. Schneider A, Bardakjian T, Reis LM, Tyler RC, Semina EV. These eye conditions can happen along with other eye conditions and medical issues. As these features can be present in children without severe structural eye defects [Zenteno et al 2006, Dennert et al 2017], they are not restricted to individuals with the full AEG syndrome [Williamson et al 2006]. Available from Genet. Identification of novel mutations and sequence variants in Recommended Evaluations Following Initial Diagnosis in Individuals with SOX2 Disorder, Treatment of Manifestations in Individuals with SOX2 Disorder. Cavallo L, Faienza MF, Fischetto R, Achermann JC, Martinez-Barbera JP, Rizzoti K, Mutations in the SOX2 gene prevent the production of functional SOX2 protein. Thalidomide treats cancer and some skin conditions. Suzuki J, Azuma N, Dateki S, Soneda S, Muroya K, Yamamoto Y, Saito R, Sano S, Nagai T, Wada H, Endo A, Urakami T, Ogata T, Fukami M. Mutation spectrum and phenotypic variation in nine patients with SOX2 abnormalities. congenital absence of the eye or eyes. Microphthalmia, anophthalmia and coloboma (MAC) are a group of birth eye conditions that affect 3 to 30 per 100,000 newborns. Extra-ocular anomalies are common. use. MRI stands for magnetic resonance imaging. The absence of the eye will cause a small bony orbit, a constricted mucosal socket, short eyelids, reduced palpebral fissure http://www.ncbi.nlm.nih.gov/books/NBK1300/. Washington) are included with each copy; (ii) a link to the original material is provided NAA10 polyadenylation signal variants cause syndromic microphthalmia. Talking to your healthcare team may help you to develop strategies to have in place to help you manage these conditions. Tests that can diagnose microphthalmia and anophthalmia before birth include: Healthcare providers arent able to provide a new eye for people born with these conditions. Females: Consider pelvic ultrasound exam &/or MRI, particularly in pubertal or postpubertal females. Julian LM, McDonald AC, Stanford WL. Here we provide a detailed description of the clinical features associated with SOX2 mutations in the five individuals with reported mutations and four newly identified cases (including the first reported SOX2 missense mutation). No phenotypes other than those discussed in this GeneReview are known to be associated with heterozygous pathogenic variants in SOX2. Reis LM, Tyler RC, Schilter KF, Abdul-Rahman O, Innis JW, Kozel BA, Schneider AS, Bardakjian TM, Lose EJ, Martin DM, Broeckel U, Semina EV. Intrafamilial clinical variability is observed in, If the genetic alteration identified in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is greater than that of the general population because of the possibility of parental germline mosaicism. Recommended Surveillance for Individuals with SOX2 Disorder. [ Read summary ] Many factors can affect how long a person with Down syndrome lives. The remaining individuals have a wide spectrum of eye malformations including the following: Thirteen individuals with loss-of-function SOX2 variants had bilateral structurally normal eyes. Status dystonicus (a movement disorder emergency in which there is prolonged, generalized, intense, and painful muscle contraction) was originally reported in individuals with bilateral anophthalmia and a specific variant (see Genotype-Phenotype Correlations and Table 7) [Gorman et al 2016]; however, other variants, including the most common SOX2 variant, were subsequently associated with this feature in two individuals with bilateral anophthalmia or bilateral optic disc abnormality [Martinez & Madsen 2019, Pilz et al 2019]. SOX2 anophthalmia syndrome is a rare disorder characterized by abnormal development of the eyes and other parts of the body. INTRODUCTION SOX2 anophthalmia syndrome is an autosomal "Anophthalmia is the absence of one or both eyes. Errichiello E, Gorgone C, Giuliano L, Iadarola B, Cosentino E, Rossato M, Kurtas NE, Delledonne M, Mattina T, Zuffardi O. SOX2: Not always eye malformations. Frequently cryptorchidism and/or micropenis in males (commonly a manifestation of hypogonadotropic hypogonadism); infrequently uterus hypoplasia and ovary or vaginal agenesis in females, Tracheoesophageal fistula and/or esophageal atresia, Delayed motor development/ learning disability, Spasticity, dystonia, or status dystonicus, For an introduction to multigene panels click, Unilateral anophthalmia or microphthalmia and a normal eye, Unilateral anophthalmia with cataract in the contralateral eye, Unilateral microphthalmia with coloboma or iris defect in the contralateral eye, Bilateral or unilateral congenital aphakia, Anterior segment dysgenesis (including sclerocornea or microcornea), A monozygotic twin with tracheoesophageal fistula and unilateral reduced palpebral fissure whose twin had unilateral anophthalmia as part of anophthalmia-esophageal atresia-genital abnormalities (AEG) syndrome [, A sibling fetus in a family with AEG syndrome, with brain anomalies and 11 rib pairs [, A woman with intellectual disability, corpus callosum agenesis, hypogonadotropic hypogonadism, vaginal agenesis, and spastic paraparesis [, A mother (with either heterozygosity or a high level of mosaicism of the, Two individuals identified in an intellectual disability cohort with mild microcornea, delayed speech and walking, esophageal stenosis, hearing deficits and mild facial hypoplasia in one; and strabismus, delayed speech, dystonic movements and spastic diplegia, hypogonadotropic hypogonadism, and corpus callosum and hippocampus malformation in the other individual [, Three individuals with mild ocular defects (esotropia, macro excavated optic disc, or thin retinal layer) and a combination of developmental delay, seizures, hypotonia or dystonia, tracheoesophageal fistula, suprasellar teratoma, and gonadal dysgenesis [. It is not yet clear which of these spectra are associated with SOX2 eye disorders, as most affected individuals have very small or absent eyes, which are thus morphologically unclassifiable. The ' SOX2 anophthalmia syndrome' encompasses sclerocornea, cataracts, persistent hyperplastic primary vitreous and optic disc dysplasia as well as non-ocular features like mental retardation, neurological abnormalities, facial dysmorphisms, post-natal growth failure, oesophageal pathology and anomalies of male genitalia [ 14, 15 ]. Education of parents/caregivers regarding common seizure presentations is appropriate. The degree of visual impairment is usually severe and consistent with the degree of structural abnormality in the eye. . Assess axial & peripheral tone to advise on likely efficacy of antispasmodic medications & procedures. Transmission of a constitutional loss-of-function pathogenic variant from a male proband to offspring has not been reported. The role of SOX2 in hypogonadotropic Williamson KA, FitzPatrick DR. Multiple pages were reviewed for this article. According to some estimates, these conditions (anophthalmia and microphthalmia) affect about 1 in 5,200 to 1 in 10,000 infants born each year in the U.S. Martinez E, Madsen EC. Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist. ED. Pavone P, Cho SY, Pratic AD, Falsaperla R, Ruggieri M, Jin DK. Prostheses: Consider optically clear expanders to stimulate growth of the orbit & periorbital tissues. However, its also possible to diagnose these conditions during pregnancy. The medical team may not be aware of the multiple ways that a rare disease can change the quality of life of the patient and family. anophthalmia-esophageal-genital (AEG) syndrome. [Google Scholar] 10. An ocularist is a provider who can make prosthetic devices like artificial eyes and conformers. Repeat MRI if change in neurologic status. They often arise in conjunction with other ocular defects such as coloboma and orbital cyst. ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and typically performed one on one with a board-certified behavior analyst. SOX2 is a single exon transcription factor previously associated with anophthalmia [ 18, 19 ], microphthalmia [ 20 ], and coloboma [ 21 ]. Disclaimer. Schneider A, Bardakjian TM, Zhou J, Hughes N, Keep R, Dorsainville D, Kherani F, Katowitz J, Schimmenti LA, Hummel M, Fitzpatrick DR, Young TL. Chassaing N, Causse A, Vigouroux A, Delahaye A, Alessandri JL, Boespflug-Tanguy O, Boute-Benejean O, Dollfus H, Duban-Bedu B, Gilbert-Dussardier B, Giuliano F, Gonzales M, Holder-Espinasse M, Isidor B, Jacquemont ML, Lacombe D, Martin-Coignard D, Mathieu-Dramard M, Odent S, Picone O, Pinson L, Quelin C, Sigaudy S, Toutain A, Thauvin-Robinet C, Kaplan J, Calvas P. Molecular findings and clinical data in a cohort of 150 patients with anophthalmia/microphthalmia. Dystonia and spasticity. [3] Microphthalmia-associated transcription factor (MITF), located on chromosome 14q32, is associated with one form of isolated microphthalmia (MCOP1). MedlinePlus also links to health information from non-government Web sites. Some issues to consider: Consider evaluation for alternative means of communication (e.g., augmentative and alternative communication [AAC]) for individuals who have expressive language difficulties. Bean LJH, Gripp KW, Amemiya A, editors. club elite rhythmic . Data were extracted from full text case reports exclusively describing SOX2 disorder (n=38) using exact string matching. In 1960, on average, persons with Down syndrome lived to be about 10 years old. Edinburgh, United Kingdom, Consultant in Pediatric Genetics, MRC Human Genetics Unit Anophthalmia/Microphthalmia (A/M) may affect one eye with the other eye being normal, or both eyes, resulting in blindness. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, et al. For example, even in extreme microphthalmia, functional retinal tissue can give some light/dark perception with or without color perception. Congenital anophthalmia is a developmental disorder in which the eye does not develop or is underdeveloped. Ceroni F, Aguilera-Garcia D, Chassaing N, Bax DA, Blanco-Kelly F, Ramos P, Tarilonte M, Villaverde C, da Silva LRJ, Ballesta-Martnez MJ, Sanchez-Soler MJ, Holt RJ, Cooper-Charles L, Bruty J, Wallis Y, McMullan D, Hoffman J, Bunyan D, Stewart A, Stewart H, Lachlan K, Fryer A, McKay V, Roume J, Dureau P, Saggar A, Griffiths M, Calvas P, Ayuso C, Corton M, Ragge NK, et al. Harding P, Brooks BP, FitzPatrick D, Moosajee M. Anophthalmia including next-generation sequencing-based approaches. Facts about Anophthalmia and Microphthalmia. When anophthalmia or microphthalmia is the only condition a baby has, it's called nonsyndromic or isolated. Kelberman D, de Castro SC, Huang S, Crolla JA, Palmer R, Gregory JW, Taylor D, Anophthalmia and microphthalmia are birth defects of a baby's eye (s). Mauri L, Franzoni A, Scarcello M, Sala S, Garavelli L, Modugno A, Grammatico P, Patrosso MC, Piozzi E, Del Longo A, Gesu GP, Manfredini E, Primignani P, Damante G, Penco S. SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia. Genital abnormalities. The information on this site should not be used as a substitute for professional medical care or advice. Shah SP, Taylor AE, Sowden JC, Ragge NK, Russell-Eggitt I, Rahi JS, Gilbert CE, et al. ), (https://www.marchofdimes.org/complications/anophthalmia-and-microphthalmia.aspx), (https://medlineplus.gov/genetics/condition/sox2-anophthalmia-syndrome/#references). Consider referral to ophthalmo-plastic surgeon for children w/anophthalmia & extreme microphthalmia.