Youll need bigger devices as your face grows. Seattle (WA): University of Washington, Seattle; 1993-2023. CMA is often used as a first step. The diagnosis of SOX2 disorder is established in a proband in whom molecular genetic testing identifies either a heterozygous intragenic SOX2 pathogenic (or likely pathogenic) variant or a deletion of 3q26.33 involving SOX2. In . Conditions that are a result of problems with fetal development are sometimes called birth defects. References SOX2 anophthalmia syndrome is estimated to affect 1 in 250,000 individuals. whenever the material is published elsewhere on the Web; and (iii) reproducers, Approximately 60% of affected individuals have a de novo genetic alteration. Hussenet T et al: 18268498: 2008: SOX2 is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest . 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. Chassaing N, Gilbert-Dussardier B, Nicot F, Fermeaux V, Encha-Razavi F, Fiorenza M, Toutain A, Calvas P. Germinal mosaicism and familial recurrence of a SOX2 mutation with highly variable phenotypic expression extending from AEG syndrome to absence of ocular involvement. 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. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click For those w/micropenis, refer to endocrinologist for consideration of eval for hypogonadotropic hypogonadism. Other names for microphthalmia include small eye syndrome and microphthalmos. An oculoplastic surgeon is a surgeon who has special training with the eyes, the eye sockets and the bones that make them up. Keywords: Anopthalmia; microphthalmia; other disorders; quality of life. Tracheoesophageal fistula was seen in the presence or absence of esophageal atresia. Once the causative genetic alteration has been identified in an affected family member (or in a parent who has a structural chromosome rearrangement involving the 3q26.33 region), prenatal testing for a pregnancy at increased risk is possible, and preimplantation genetic testing for SOX2 disorder may be possible, depending on the specific familial genetic alteration. To establish the extent of disease and needs in an individual diagnosed with SOX2 disorder, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to diagnosis) are recommended. Tziaferi V, Kelberman D, Dattani MT. SOX2 plays a critical role Extension of the mutational and clinical spectrum of SOX2 related disorders: Description of six new cases and a novel association with suprasellar teratoma. You may hear some people say that anophthalmia and microphthalmia are examples of eye birth defects.. ED. in the pituitary, forebrain, and eye during human embryonic development. 2008;2(4-5):194-9. doi: 10.1159/000152035. 2007 Nov . The mutation of the sox2 gene causes sox2 Anophthalmia syndrome. An ocularist is a provider who can make prosthetic devices like artificial eyes and conformers. SOX2 disorder comprises a phenotypic spectrum that can include anophthalmia and/or microphthalmia, brain malformations, developmental delay/ intellectual disability, esophageal atresia, hypogonadotropic hypogonadism (manifest as cryptorchidism and micropenis in males, gonadal dysgenesis infrequently in females, and delayed puberty in both sexes), pituitary hypoplasia, postnatal growth delay, hypotonia, seizures, and spastic or dystonic movements. 8 color. These eye problems can cause significant vision loss. risk assessment and the use of family history and genetic testing to clarify genetic GeneReviews staff has selected the following disease-specific and/or umbrella Fielder A, Ainsworth J, Moore A, Read S, Uddin J, Laws D, Pascuel-Salcedo D, ~50% of affected individuals had DD or autism. Br J Ophthalmol. In bilateral anophthalmia, both eyes are missing. Williamson KA, Hever AM, Rainger J, Rogers RC, Magee A, Fiedler Z, Keng WT, Sharkey FH, McGill N, Hill CJ, Schneider A, Messina M, Turnpenny PD, Fantes JA, van Heyningen V, FitzPatrick DR. Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome. Congenital anophthalmia is a developmental disorder in which the eye does not develop or is underdeveloped. Thalidomide treats cancer and some skin conditions. Additionally, feeding difficulty or gastroesophageal reflux was observed in multiple individuals. Schneider A, Young TL. . Ma AS, Grigg JR, Ho G, Prokudin I, Farnsworth E, Holman K, Cheng A, Billson FA, Martin F, Fraser C, Mowat D, Smith J, Christodoulou J, Flaherty M, Bennetts B, Jamieson RV. About 10 percent to 15 percent of people with anophthalmia in both eyes have SOX2 anophthalmia syndrome. The following descriptions are based on these key reports, together with all other published cases and the authors' unpublished data. . How are genetic conditions treated or managed? People can be born with one or two small eyes (microphthalmia) or without one or both eyes (anophthalmia). Seizures were observed in 22 individuals. Approximately 2/3 of all cases of anophthalmia are determined to be of genetic basis. sox2 anophthalmia syndrome life expectancy. How do you know if your baby has anophthalmia or microphthalmia? However, its also possible to diagnose these conditions during pregnancy. use. These major malformations constitute a surgical emergency. Select Features of SOX2 Disorder: Frequency of Human Phenotype Ontology (HPO) Terms. Variants listed in the table have been provided by the authors. Recommended Surveillance for Individuals with SOX2 Disorder. Note: The severity of disease and specific clinical findings vary and cannot be accurately predicted by the family history or results of molecular genetic testing. contact: ude.wu@tssamda. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Your provider will be able to tell if your baby has microphthalmia or anophthalmia by looking carefully during a physical examination and doing an eye exam. Microcornea: A microcornea is a cornea thats very small. Endocrinol Metab. Williamson KA, FitzPatrick DR. It is also possible that complete failure of optic vesicle formation results in anophthalmia without optic nerve formation. Sharkey FH, McGill N, Hill CJ, Schneider A, Messina M, Turnpenny PD, Fantes JA, Children and adults who have a rare disease and their caregivers are encouraged to talk about their needs with the medical team and to reach out for the support they require. 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. Genes of Interest in the Differential Diagnosis of SOX2 Disorder. Genetic counseling is the process of providing individuals and families with Zanolli M, Oporto JI, Verdaguer JI, Lpez JP, Zacharas S, Romero P, Ossandn D, Denk O, Acua O, Lpez JM, Stevenson R, lamos B, Iturriaga H. Genetic testing for inherited ocular conditions in a developing country. It mostly happens in the. [updated 2020 Jul 30]. Gorman KM, Lynch SA, Schneider A, Grange DK, Williamson KA, FitzPatrick DR, King MD. Brain MRI. 2006 Feb 23 [Updated 2020 Jul 30]. Status dystonicus, hyperpyrexia, and acute kidney injury in a patient with SOX2-anophthalmia syndrome. sox2 anophthalmia syndrome life expectancy. Epub 2006 Mar 16. MRC Institute of Genetics and Molecular Medicine sox2 anophthalmia syndrome life expectancy golf lessons west seattle what race is tecna from winx club sox2 anophthalmia syndrome life expectancy 16 de junio de 2022 Polyadenylation signal variants are assoc w/familial anophthalmia. Novel mutations in PAX6, OTX2 and NDP in anophthalmia, microphthalmia and coloboma. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. For more information, see the GeneReviews Copyright Notice and Usage 3 bedroom houses for rent in fort myers. It has been called also the SOX 2 anophthalmia syndrome 3 due to the frequent mutations and/or deletions found in the SOX2 gene. The ZR13 OBD2 Code Reader by Zurich is the ultimate in code readers. Male genital abnormalities include undescended testes (cryptorchidism) and an unusually small penis (micropenis). Abnormal development of these structures causes the signs and symptoms of SOX2 anophthalmia syndrome. Assess for sensorineural & conductive hearing loss. Anophthalmos, microphthalmos, and typical coloboma in the United Kingdom: a prospective study of incidence and risk. here. More detailed information for clinicians ordering genomic testing can be found here. Get useful, helpful and relevant health + wellness information, 9500 Euclid Avenue, Cleveland, Ohio 44195 |, Important Updates + Notice of Vendor Data Event. Researchers think that the changes in genes and chromosomes may combine with environmental factors to result in conditions present at birth. Consider need for positioning & mobility devices & disability parking placard. SOX2 anophthalmia syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In 1960, on average, persons with Down syndrome lived to be about 10 years old. See Genetic Counseling. SOX2 anophthalmia syndrome is estimated to affect 1 in 250,000 individuals. Information on exact seizure type is limited, but most appeared to be grand mal tonic-clonic seizures that appeared in early childhood and responded well to standard anticonvulsant medication. 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]. What is the prognosis of a genetic condition? The term anophthalmia is often used interchangeably with severe microphthalmia because individuals with no visible eyeballs typically have some remaining eye tissue. Sporadic and familial congenital cataracts: mutational spectrum and new diagnoses using next-generation sequencing. as in some patients with SOX2 . Microphthalmia, Syndromic . Policy. Esophageal atresia or stenosis was reported in nine and three individuals, respectively. For details about heterozygous deletions of 3q26.33 involving SOX2, see Molecular Genetics. The SOX2-associated ocular malformations are variable in . Almost all SOX2 pathogenic variants reported to date appear to represent heterozygous loss of function; thus, it is difficult to draw genotype-phenotype correlations. Coming to a Cleveland Clinic location?Hillcrest Cancer Center check-in changesCole Eye entrance closingVisitation, mask requirements and COVID-19 information, Notice of Intelligent Business Solutions data eventLearn more, Microphthalmia and anophthalmia are both congenital conditions that affect the eyes. This is a rare disorder that can cause a child to be born without eyeballs. Conformers: These are devices that fit into the eye socket to help your eye socket and face develop more typically. ), (https://www.marchofdimes.org/complications/anophthalmia-and-microphthalmia.aspx), (https://medlineplus.gov/genetics/condition/sox2-anophthalmia-syndrome/#references). Some babies are born with these conditions due to genetic changes. These conditions may also occur with other eye conditions or medical problems elsewhere on the body. Schneider A, Bardakjian T, Reis LM, Tyler RC, Semina EV. Edinburgh, United Kingdom, Consultant in Pediatric Genetics, MRC Human Genetics Unit MRI stands for magnetic resonance imaging. If CMA does not detect a copy number variant, genome sequencing and/or exome sequencing may be used. Shah SP, Taylor AE, Sowden JC, Ragge NK, Russell-Eggitt I, Rahi JS, Gilbert CE, et al. 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. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs. Anophthalmia-esophageal atresia-genital abnormalities (AEG) syndrome was previously reported to be a distinct disorder, but is now known to be associated in some individuals with heterozygous pathogenic loss-of-function variants in SOX2 [Williamson et al 2006, Zenteno et al 2006]; thus, it appears that esophageal atresia with or without tracheoesophageal fistula is a feature of SOX2 disorder and not a separate condition. 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. 2006 May W/attention to brain/pituitary malformations, optic nerve/chiasm/tract. david millward security; swarovski habicht 10x40; east hanover police scanner; sample complaint car accident negligence. Mutations in the SOX2 gene cause SOX2 anophthalmia syndrome. 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. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Last reviewed by a Cleveland Clinic medical professional on 09/07/2022. About 10 percent to 15 percent of people with anophthalmia in both eyes have SOX2 syndrome. Its a question of managing these conditions and any other conditions that might occur with them. Once the causative genetic alteration has been identified in an affected family member (or a parent is known to have a structural chromosome rearrangement involving the 3q26.33 region), prenatal testing for a pregnancy at increased risk is possible and preimplantation genetic testing for SOX2 disorder may be possible, depending on the specific familial variant. The diagnosis of SOX2 disorder is established in a proband in whom molecular genetic testing identifies either a heterozygous intragenic SOX2 pathogenic (or likely pathogenic) variant or a deletion that is intragenic or a deletion of 3q26.33 involving SOX2 (see Table 1). SOX2-specific laboratory technical considerations. Lenz microphthalmia syndrome: In addition to small eyes, people with this syndrome may have uncontrolled eye movements, learning issues and problems with the skeletal and urinary systems. GeneReviews(R) [Internet]. MRC Institute of Genetics and Molecular Medicine Note: Testing of parental DNA may not detect all instances of somatic and germline mosaicism. Erratum In: Hum Mol Esophageal atresia with or without tracheoesophageal fistula. SOX2 eye defects are usually bilateral, severe, and apparent at birth or on routine prenatal ultrasound examination. SOX2 (OMIM 184429) belongs to the SOX family of transcription factors that contain a 79-amino acid high mobility group (HMG) box DNA-binding domain similar to that found in the sex-determining gene SRY (OMIM 480000) (1, 2). Schneider A, Bardakjian TM, Zhou J, Hughes N, Keep R, Dorsainville D, Kherani F, Katowitz J, Schimmenti LA, Hummel M, Fitzpatrick DR, Young TL. The term anophthalmia is often used . Centers for Disease Control and Prevention. Hearing device can be helpful but no treatment is available for the eyeball malformations. SOX2 mutation causes anophthalmia, hearing loss, and brain anomalies. SOX2 encodes the transcription factor SOX2 (317 amino acids) which has an HMG DNA-binding domain (amino acids 40-111), a partner-binding region, and a C-terminal transactivation region. Correcting refractive error is necessary to treat any sign of. In two of these, FISH studies identified sub-microscopic deletions involving a minimum of 328 Kb and 550 Kb. SOX2 anophthalmia syndrome Luisa Sanctis 2005, American Journal of Medical Genetics Part A Microphthalmia (small eye), anophthalmia (absent eye), and coloboma (failure of optic fissure closure) (MAC) are commonly associated eye malformations with a combined birth incidence of about 2 per 10,000 . Epub 2008 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. Sensorineural hearing loss. Additional services can help families work together to improve life for their child. However, there are treatments that include: Theres no way to completely eliminate your risk of microphthalmia and anophthalmia, but there are ways to make pregnancy safer: Theres no cure for microphthalmia or anophthalmia. One of the genetic causes for Anophthalmia is the sox2 gene. congenital absence of the eye or eyes. Seven had no ocular defects noted and six had mild ocular defects, including the following: Anterior pituitary hypoplasia. Sox2 anophthalmia syndrome is caused by a mutation in the Sox2 gene that does not allow it to produce the Sox2 protein that regulates the activity of other genes by binding to certain regions of DNA. Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability. driver refresher course for seniors; vawa cases approved 2022 immihelp; "My husband and I are not carriers; our tests were completely normal. i told him i miss him and he said aww; la porosidad es una propiedad extensiva o intensiva Note: There may not be clinical trials for this disorder. SOX2 anophthalmia syndrome Clinical Information Anophthalmos-. and their families. recurrence of SOX2 anophthalmia syndrome: phenotypically normal mother with two [ Read summary ] Many factors can affect how long a person with Down syndrome lives. Posted on June 29, 2022 Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas comprehensive genomic testing does not. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities. Specific recommendations regarding type of therapy can be made by a developmental pediatrician. Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary. genomic testing, which does not require the clinician to determine which gene is likely involved, is an option when SOX2 disorder is not an easily achievable diagnosis. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided. Epub 2008 Nov SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions. Its a specialized imaging test that may be helpful in evaluating for fetal congenital anomalies and associated complications. Ophthalmol. "In simple terms these Chromosomes are snapped, swapped and a piece has gone missing," Sarah explains. 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). 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. SOX2 @ The Human Genetics Unit Edinburgh U.K. Gene-targeted deletion/duplication analysis, ~24% (~21% that could also be resolved by CMA & ~3% that are below the limit of detection by CMA), Bilateral microphthalmia &/or anophthalmia, Bilateral anophthalmia, optic disc aplasia/hypoplasia, Bilateral microphthalmia, coloboma, cataract, Unilateral or bilateral microphthalmia &/or anophthalmia. Washington) are included with each copy; (ii) a link to the original material is provided SOX2 anophthalmia syndrome. See a healthcare provider before you get pregnant and work together so you can be as healthy as possible before and during your pregnancy. Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including SOX2) that cannot be detected by sequence analysis. Surveillance: Routine follow up with specialists managing the vision, educational, endocrine, and neurologic manifestations. Intellectual ability is highly variable, ranging from normal to profound learning disability, with the majority having moderate learning disability. The absence of this protein disrupts the activity of genes that are essential for the development of the eyes and other parts of the body. Heterozygous, de novo, loss-of-function mutations in SOX2 have been shown to cause bilateral anophthalmia. MedlinePlus links to health information from the National Institutes of Health and other federal government agencies. football players born in milton keynes; ups aircraft mechanic test. Microphthalmia-anophthalmia-coloboma (MAC) was used as an umbrella term for the spectrum of severe eye malformations in early publications describing SOX2 eye disorders. Blackburn PR, Chacon-Camacho OF, Ortiz-Gonzlez XR, Reyes M, Lopez-Uriarte GA, Zarei S, Bhoj EJ, Perez-Solorzano S, Vaubel RA, Murphree MI, Nava J, Cortes-Gonzalez V, Parisi JE, Villanueva-Mendoza C, Tirado-Torres IG, Li D, Klee EW, Pichurin PN, Zenteno JC. Anophthalmos-. The SOX2 phenotypes include a patient with anophthalmia, oesophageal abnormalities and horseshoe kidney, and a patient with a retinal dystrophy implicating SOX2 in retinal development. . People with SOX2 anophthalmia syndrome are usually born without eyeballs (anophthalmia), although some individuals have small eyes (microphthalmia). Edinburgh, United Kingdom, Malformations of the ears, teeth, fingers, skeleton, or genitourinary system, Mild-to-severe ID or DD in ~60% of affected males, Incl best corrected visual acuity, assessment of refractive error, fundus exam. This condition is caused by an extra X chromosome in each of a female's cells. Both conditions are rare, and can cause vision loss or blindness. Genital abnormalities. The Human Phenotype Ontology (HPO) enables use of precise, standardized, computationally accessible terms to describe phenotypic abnormalities. 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. They also help with socket and face development and can help with cosmetic concerns. [3] Microphthalmia-associated transcription factor (MITF), located on chromosome 14q32, is associated with one form of isolated microphthalmia (MCOP1). National Library of Medicine. They may also. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133583/), Visitation, mask requirements and COVID-19 information, Coloboma: A coloboma means that tissue is missing in the eye. 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 role of SOX2 in hypogonadotropic hypogonadism. Treatment Depending upon the severity of malformations, life expectancy can be normal but some patients have died in the neonatal period. Anophthalmia and microphthalmia are eye conditions that people are born with. These early intervention services will help babies learn to walk, talk and interact with others. Recurrence of SOX2 anophthalmia syndrome with gonosomal mosaicism in a phenotypically normal mother. Williamson KA, Yates TM, FitzPatrick DR. SOX2 Disorder. Extra-ocular anomalies are common. support organizations and/or registries for the benefit of individuals with this disorder University of Edinburgh HGNC; 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). 2008 Mar 24;14:583-92. The phenotypic spectrum of SOX2 disorder includes anophthalmia and/or microphthalmia, brain malformations, developmental delay/ intellectual disability, esophageal atresia, hypogonadotropic hypogonadism (manifest as cryptorchidism and micropenis in males, gonadal dysgenesis infrequently in females, and delayed puberty in both sexes), pituitary hypoplasia, postnatal growth delay, hypotonia, seizures, and spastic or dystonic movements. Takagi M, Narumi S, Asakura Y, Muroya K, Hasegawa Y, Adachi M, Hasegawa T. A novel mutation in SOX2 causes hypogonadotropic hypogonadism with mild ocular malformation. information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them Williamson KA, Hall HN, Owen LJ, Livesey BJ, Hanson IM, Adams GGW, Bodek S, Calvas P, Castle B, Clarke M, Deng AT, Edery P, Fisher R, Gillessen-Kaesbach G, Heon E, Hurst J, Josifova D, Lorenz B, McKee S, Meire F, Moore AT, Parker M, Reiff CM, Self J, Tobias ES, Verheij JBGM, Willems M, Williams D, van Heyningen V, Marsh JA, FitzPatrick DR. Recurrent heterozygous PAX6 missense variants cause severe bilateral microphthalmia via predictable effects on DNA-protein interaction. SOX2 disorder, caused by an intragenic SOX2 pathogenic variant or a deletion of 3q26.33 involving SOX2, is an autosomal dominant disorder. 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 ]. Sex Dev. See our, URL of this page: https://medlineplus.gov/genetics/condition/sox2-anophthalmia-syndrome/. silobration vendor application 2022dream about someone faking their death Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. If the genetic alteration identified in the proband is not identified in either parent, the following possibilities should be considered: The proband inherited a pathogenic variant from a parent with germline mosaicism. Status dystonicus in two patients with SOX2-anophthalmia syndrome and nonsense mutations. The degree of visual impairment is usually severe and consistent with the degree of structural abnormality in the eye. Identification of novel mutations and sequence variants in the SOX2 and CHX10 genes in patients with anophthalmia/microphthalmia. sox2 anophthalmia syndrome life expectancy BACKGROUND: Developmental eye anomalies, which include anophthalmia (absent eye) or microphthalmia (small eye) are an important cause of severe visual impairment in infants and young children.