Measurement of weight, length/height, & head circumference, Complete ophthalmologic exam by experienced pediatric ophthalmologist, Males: Assessment for micropenis &/or cryptorchidism. Mutations in the SOX2 gene cause SOX2 anophthalmia syndrome. Congenital anophthalmia and microphthalmia are rare developmental defects of the globe. in the fellow eye. About 10 percent to 15 percent of people with anophthalmia in both eyes have SOX2 anophthalmia syndrome. support organizations and/or registries for the benefit of individuals with this disorder A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text. 3 bedroom houses for rent in fort myers. The risk to other family members depends on the genetic status of the proband's parents: if a parent has the causative genetic alteration or a balanced structural chromosome rearrangement, the parent's family members may be at risk. Ophthalmo-acromelic syndrome is a condition that results in malformations of the eyes, hands, and feet. Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate. Fielder A, Ainsworth J, Moore A, Read S, Uddin J, Laws D, Pascuel-Salcedo D, chromosome locus from Always go to your appointments, even if you feel fine. The following section deals with genetic Hearing aids may be helpful per audiologist/otolaryngologist. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist. 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 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 . Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). Education of parents/caregivers regarding common seizure presentations is appropriate. Microphthalmia is when one or both of a baby's eyes are small. Disclaimer. Occasionally hypospadias is observed. Contact a health care provider if you have questions about your health. risk assessment and the use of family history and genetic testing to clarify genetic Symptoms include poor vision or even complete vision loss. Williamson KA, Yates TM, FitzPatrick DR. SOX2 Disorder. This is a rare disorder that can cause a child to be born without eyeballs. There are early intervention services to help your child learn and support groups to help your family and your child succeed. david millward security; swarovski habicht 10x40; east hanover police scanner; sample complaint car accident negligence. This phenomenon is called germline mosaicism. [3] Microphthalmia-associated transcription factor (MITF), located on chromosome 14q32, is associated with one form of isolated microphthalmia (MCOP1). The ability to determine the size of the deletion/duplication depends on the type of microarray used and the density of probes in the 3q26.33 region. This includes prescription products and supplements. SOX2-specific laboratory technical considerations. There is no cure. 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). Thalidomide treats cancer and some skin conditions. Repeat MRI if change in neurologic status. Abnormal development of these structures causes the signs and symptoms of SOX2 anophthalmia syndrome. Inheritance was observed as de novo constitutive or de novo mosaic events, or, less frequently, from parents with constitutional duplications (see DECIPHER). (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. Prosthetic eyes: Prosthetic eyes are placed in empty eye sockets. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. 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. Epub 2006 Mar 16. Anophthalmia means that one or both eyes dont develop at all so they are missing. . MRC Institute of Genetics and Molecular Medicine club elite rhythmic . National Library of Medicine. Erratum In: Hum Mol The features of this condition are present from birth. Seven had no ocular defects noted and six had mild ocular defects, including the following: Anterior pituitary hypoplasia. in the pituitary, forebrain, and eye during human embryonic development. Anophthalmia is when a baby is born without one or both of their eyes. 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. Severe genital but no major ocular anomalies in a female patient with the recurrent c.70del20 variant. Seven children had apparently nonprogressive moderate sensorineural hearing loss requiring hearing aids. GARD: 19 Anophthalmia plus syndrome (APS) is a very rare syndrome that involves malformations in multiple organs of the body. To use the sharing features on this page, please enable JavaScript. The term anophthalmia is often used . ethical issues that may arise or to substitute for consultation with a genetics Frequency refers to the number of times the term was used in all included case reports. The N-terminal region is of unknown function and contains short polyglycine and polyalanine repeats. For clarity, excerpts It is so rare it occurs in one in 250,000 people. Endocrinol Metab. Chromosomal aberrations involving this region of chromosome 3 have also been found. Data were extracted from full text case reports exclusively describing SOX2 disorder (n=38) using exact string matching. The role of SOX2 in hypogonadotropic 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. com. SOX2 syndrome is estimated to affect 1 in 250,000 individuals. A minority of affected individuals develop early continual dystonic posturing that is similar to that seen in dystonic cerebral palsy but without evidence of basal ganglia injury on neuroimaging. A/M is rare, but the exact incidence is unknown. HPO terms that appear fewer than four times were excluded. As the lung develops, cells become specified and differentiate into the various cell lineages. They often arise in conjunction with other ocular defects such as coloboma and orbital cyst. 2007 Nov 26;2:47. doi: 10.1186/1750-1172-2-47. This condition is caused by an extra X chromosome in each of a female's cells. There's no treatment that can create a new eye or bring vision . ~50% of affected individuals had DD or autism. 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. Mechanism of disease causation. 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. Get useful, helpful and relevant health + wellness information, 9500 Euclid Avenue, Cleveland, Ohio 44195 |, Important Updates + Notice of Vendor Data Event. The absence of the eye will cause a small bony orbit, a constricted mucosal socket, short eyelids, reduced palpebral fissure Cleveland Clinic is a non-profit academic medical center. In two of these, FISH studies identified sub-microscopic deletions involving a minimum of 328 Kb and 550 Kb. There are other things that may be factors in these eye conditions, including: In a newborn child, your provider can diagnose anophthalmia and microphthalmia through an examination. References Available from It is also possible that complete failure of optic vesicle formation results in anophthalmia without optic nerve formation. Assess axial & peripheral tone to advise on likely efficacy of antispasmodic medications & procedures. The life expectancy of people with Down syndrome increased dramatically between 1960 and 2007. The mutation of the sox2 gene causes sox2 Anophthalmia syndrome. The term "SOX2 disorder" is used in this GeneReview to refer to the complete phenotypic spectrum associated with heterozygous SOX2 pathogenic variants. Hussenet T et al: 18268498: 2008: SOX2 is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest . Consider referral to ophthalmo-plastic surgeon for children w/anophthalmia & extreme microphthalmia. 1;15(9):1413-22. doi: 10.1093/hmg/ddl064. Data are compiled from the following standard references: gene from SOX2 eye defects are usually bilateral, severe, and apparent at birth or on routine prenatal ultrasound examination. 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. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. Novel SOX2 mutations and genotype-phenotype correlation in anophthalmia and microphthalmia. The SOX2 protein regulates the activity of other genes, especially those that are important for normal development of the eyes. MRC Human Genetics Unit Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. genomic testing (CMA, exome sequencing, exome array, genome sequencing) depending on the phenotype. Genital anomalies are present in only 33% of reported AEG. Verma AS, Fitzpatrick DR. Anophthalmia and microphthalmia. 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. hereby granted to reproduce, distribute, and translate copies of content materials for Zhou J, Kherani F, Bardakjian TM, Katowitz J, Hughes N, Schimmenti LA, i told him i miss him and he said aww; la porosidad es una propiedad extensiva o intensiva . Both the globe (human eye) and the ocular The majority of SOX2 mutations identified appear to arise de novo in probands ascertained through the presence of anophthalmia or microphthalmia. 2008 Nov 1;146A(21):2794-8. doi: Schneider A, Young TL. Hearing device can be helpful but no treatment is available for the eyeball malformations. While both eyes are usually affected in SOX2 anophthalmia syndrome, one eye may be more affected than the other. Abstract Heterozygous, de novo, loss-of-function mutations in SOX2 have been shown to cause bilateral anophthalmia. The ZR13 OBD2 Code Reader by Zurich is the ultimate in code readers. 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. football players born in milton keynes; ups aircraft mechanic test. Need for social work involvement for parental support. SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions. There are many ways to receive support: Bilateral anophthalmia and/or microphthalmia, Unilateral anophthalmia or microphthalmia, Genital abnormalities. noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright ( 1993-2023 University of ), (https://www.marchofdimes.org/complications/anophthalmia-and-microphthalmia.aspx), (https://medlineplus.gov/genetics/condition/sox2-anophthalmia-syndrome/#references). CMA is often used as a first step. Gorman KM, Lynch SA, Schneider A, Grange DK, Williamson KA, FitzPatrick DR, King MD. http://www.ncbi.nlm.nih.gov/books/NBK1300/. 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). Feb 19. Heterozygous, de novo, loss-of-function mutations in SOX2 have been shown to cause bilateral anophthalmia. Bilateral anophthalmia and brain malformations caused by a 20-bp deletion in the SOX2 gene. the diversifying clinical signs. It is an early marker of neurulation in chick embryos and shows site- and stage-specific expression in the developing nervous system, genital ridge, and foregut in all vertebrates studied. sox2 anophthalmia syndrome life expectancy Isgho Votre ducation notre priorit The SOX2 anophthalmia syndrome is emerging as a clinically recognizable disorder that has been identified in 10-15% of individuals with bilateral anophthalmia. Certain defects such as those of the heart, palate and esophagus can be surgically repaired. Gerth-Kahlert et al [2013], Chassaing et al [2014], Suzuki et al [2014], Mauri et al [2015], Zanolli et al [2020]. whenever the material is published elsewhere on the Web; and (iii) reproducers, Familial recurrence of SOX2 anophthalmia syndrome: phenotypically normal mother with two affected daughters. Familial 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. Some babies are born with these conditions due to genetic changes. True or primary anophthalmia is incompatible with life . 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 [. 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. SOX2 anophthalmia syndrome is a rare disorder characterized by abnormal development of the eyes and other parts of the body. SOX1 (OMIM 602148), SOX2, and SOX3 (OMIM 313430) belong to the B1 subfamily and are expressed in various phases of embryonic development and cell differentiation, in which . Optic fissure closure defects have been reported but are not a common feature. If lens induction is impaired, the predicted clinical spectrum would be congenital cataract > microphthalmia > anophthalmia. SOX2 anophthalmia syndrome Also known as: AEG syndrome, Anophthalmia-esophageal-genital syndrome, SOX2-related eye disorders, syndromic microphthalmia 3 About Description and symptoms Communities Support groups for Sox2 Anophthalmia Syndrome Providers Healthcare providers in the area Research This process is controlled by specific transcription factors, such as the SRY-related HMG-box genes SOX2 and SOX21, that are activated or repressed through . Correcting refractive error is necessary to treat any sign of. For questions regarding permissions or whether a specified use is allowed, The most common findings in affected individuals are anophthalmia (absence of one or both eyes) or severe microphthalmia (abnormally small eyes), and cleft lip and/or cleft palate. 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. Genes associated with ocular manifestations frequently observed in SOX2 disorder (with or without nonocular comorbidities) are summarized in Table 3. SOX2 plays a critical role in the pituitary, forebrain, and eye during human embryonic development. Facts about Anophthalmia and Microphthalmia. This gene provides instructions for making a protein that plays a critical role in the formation of many different tissues and organs during embryonic development. In males, micropenis and cryptorchidism (often a manifestation of congenital hypogonadotropic hypogonadism) are common. SOX2 anophthalmia syndrome: 12 new cases Youll need bigger devices as your face grows. Microcornea: A microcornea is a cornea thats very small. Anophthalmia is the absence of one or both eyes. Disclaimer, Developmental Delay/ Intellectual Disability Management Issues. 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. 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. 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. Approximately 60% of individuals diagnosed with, One individual with unilateral anophthalmia had a similarly affected mother [, Maternal transmission of an identical and recurrent pathogenic variant has been observed in two families: a four-generation family with eye defects ranging from microcornea or retinal tuft with refractive error to bilateral anophthalmia [, A mother with a pathogenic variant (heterozygous or high-level mosaicism) who was minimally affected with isolated hypogonadotropic hypogonadism had two affected children: one with bilateral anophthalmia and subtle endocrine abnormalities and the other with unilateral microphthalmia with coloboma [, Maternal somatic/germline mosaicism was reported in four families with sib recurrence of, Recommendations for the evaluation of the parents of a proband with an apparent, Molecular genetic testing (ideally of parental DNA extracted from more than one tissue source, e.g., leukocytes and buccal cells) if the proband has an intragenic. Deml B, Reis LM, Lemyre E, Clark RD, Kariminejad A, Semina EV. The majority of affected individuals have some evidence of hypothalamic-pituitary axis dysfunction when detailed measurement of growth hormone and gonadotropins is undertaken [Tziaferi et al 2008]. GeneReviews(R) [Internet]. Epub 2008 Treatment Depending upon the severity of malformations, life expectancy can be normal but some patients have died in the neonatal period. Make sure you get prenatal care (care before birth) early and consistently. For a review article see Julian et al [2017]. Your provider may suggest genetic testing before you get pregnant after discussing your medical history and your family history. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas comprehensive genomic testing does not. People with SOX2 anophthalmia syndrome are usually born without eyeballs (anophthalmia), although some individuals have small eyes (microphthalmia). See Genetic Counseling. Some affected individuals have inherited the genetic alteration from either an affected mother (transmission from an affected father to child has not been reported to date) or an unaffected parent with germline mosaicism. Centers for Disease Control and Prevention. Fetal MRI. The eyes are often absent or severely underdeveloped (anophthalmia), or they may be abnormally small (microphthalmia). van Heyningen V, FitzPatrick DR. Mutations in SOX2 cause 16,17 Systemic associations included anophthalmia-plus syndrome, 19 Waardenburg-type ophthalmo-acromelic syndrome, 20 otocephaly, 16 limb body wall complex, 17 and holoprosencephaly. As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. 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. Beyond that, private supportive therapies based on the affected individual's needs may be considered. University of Edinburgh Schneider A, Bardakjian T, Reis LM, Tyler RC, Semina EV. 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. Faivre L, Williamson KA, Faber V, Laurent N, Grimaldi M, Thauvin-Robinet C, Durand C, Mugneret F, Gouyon JB, Bron A, Huet F, Hayward C. Heyningen Vv, Fitzpatrick DR. Br J Ophthalmol. OMIM; Johnston JJ, Williamson KA, Chou CM, Sapp JC, Ansari M, Chapman HM, Cooper DN, Dabir T, Dudley JN, Holt RJ, Ragge NK, Schffer AA, Sen SK, Slavotinek AM, FitzPatrick DR, Glaser TM, Stewart F, Black GC, Biesecker LG. 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. How can gene variants affect health and development? Pavone P, Cho SY, Pratic AD, Falsaperla R, Ruggieri M, Jin DK. MRC Institute of Genetics and Molecular Medicine driver refresher course for seniors; vawa cases approved 2022 immihelp; mutual life insurance companies list. ED. 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. 2008 May;93(5):1865-73. doi: 10.1210/jc.2007-2337. Anophthalmia presents as a small, bony orbit, malar prominence, reduced palpebral fissure, short eyelids, and a constricted mucosal socket. See Molecular Genetics for information on variants detected in this gene. OT = occupational therapist; PT = physical therapist. 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 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]. SOX2 anophthalmia syndrome is estimated to affect 1 in 250,000 individuals. Consider referral to urologist for cryptorchidism or other genital malformations. For information on nonmedical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy Foundation Toolbox. professional. 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. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Orphanet J Rare make informed medical and personal decisions. HGNC; status for family members; it is not meant to address all personal, cultural, or This may be an inappropriate acronym, as it implies that coloboma is an intrinsic part of all microphthalmia, which is not the case: coloboma has been reported but is not a common feature. Some people with this condition are born with a blocked esophagus (esophageal atresia), which is often accompanied by an abnormal connection between the esophagus and the trachea (tracheoesophageal fistula). affected daughters. 8 color. [ Read summary ] Many factors can affect how long a person with Down syndrome lives. Triple X syndrome. sox2 anophthalmia syndrome life expectancy. "My husband and I are not carriers; our tests were completely normal. here. 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. Permission is OMIM Entries for SOX2 Disorder (View All in OMIM). 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). Duplications encompassing SOX2, ranging from 40 kb to 104 Mb, do not appear to cause structural eye defects, but are associated with other features of SOX2 disorder: developmental delay, intellectual disability, motor delay, hypotonia, and gastroesophageal reflux. For details about heterozygous deletions of 3q26.33 involving SOX2, see Molecular Genetics. Male genital abnormalities include undescended testes (cryptorchidism) and an unusually small penis (micropenis). 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]. They may also. For an introduction to comprehensive genomic testing click here. However, its also possible to diagnose these conditions during pregnancy. GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen.hgvs.org). Malformation and/or gray matter heterotopia of the mesial temporal structures (hippocampal and parahippocampal), pituitary hypoplasia, and agenesis or dysgenesis of the corpus callosum are core features of SOX2 disorder. Sporadic and familial congenital cataracts: mutational spectrum and new diagnoses using next-generation sequencing. A short animation explaining MAC. Reported heterozygous deletions of 3q26.33 involving SOX2 (~2%-3% of affected individuals, increasing to ~20% of affected individuals with bilateral anophthalmia/severe microphthalmia) [Williamson & FitzPatrick 2014; Author, unpublished data] include: Initial Posting: February 23, 2006; Last Update: July 30, 2020. 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.