For information on selection criteria, click here. How do people inherit SOX2 syndrome? Permission is of GeneReviews chapters for use in lab reports and clinic notes are a permitted Anophthalmia is the absence of one or both eyes. Edinburgh, United Kingdom, Consultant in Pediatric Genetics, MRC Human Genetics Unit Its important to have a healthcare team if you or your child has microphthalmia or anophthalmia. With the current widespread use of advanced molecular genetic testing, it is apparent that the clinical spectrum associated with SOX2 pathogenic variants includes anophthalmia and/or microphthalmia as well as phenotypes with minimal or absent ocular findings. Genetic Testing Registry: Anophthalmia/microphthalmia-esophageal atresia syndrome, National Organization for Rare Disorders (NORD). Heterozygous, de novo, loss-of-function mutations in SOX2 have been shown to cause bilateral anophthalmia. Hussenet T et al: 18268498: 2008: SOX2 is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest . For details about heterozygous deletions of 3q26.33 involving SOX2, see Molecular Genetics. Treatment Depending upon the severity of malformations, life expectancy can be normal but some patients have died in the neonatal period. Facts about Anophthalmia and Microphthalmia. The term anophthalmia is often used . Developmental Disabilities Administration (DDA) enrollment is recommended. 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. . Erratum In: Hum Mol Ragge NK, Lorenz B, Schneider A, Bushby K, de Sanctis L, de Sanctis U, Salt A, Collin JR, Vivian AJ, Free SL, Thompson P, Williamson KA, Sisodiya SM, van Heyningen V, Fitzpatrick DR. SOX2 anophthalmia syndrome. The degree of visual impairment is usually severe and consistent with the degree of structural abnormality in the eye. Ted has Sox2 anophthalmia syndrome, caused by an unbalanced translocation of Chromosomes 3 and 14 and a microdeletion of Chromosome 3. 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. See a healthcare provider before you get pregnant and work together so you can be as healthy as possible before and during your pregnancy. This is an autosomal dominant disorder secondary to heterozygous mutations in the SOX2 gene (3q26.33). These eye problems can cause significant vision loss. augmentative and alternative communication, GeneReviews Copyright Notice and Usage Education of parents/caregivers regarding common seizure presentations is appropriate. 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). 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. In the US, developmental preschool through the local public school district is recommended. Occasionally hypospadias is observed. 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 . New GJA8 variants and phenotypes highlight its critical role in a broad spectrum of eye anomalies. 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. In general, retina tissue that is present has some functional activity. Seven children had apparently nonprogressive moderate sensorineural hearing loss requiring hearing aids. They may also. University of Edinburgh For information on nonmedical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy Foundation Toolbox. Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel, and chromosomal microarray analysis [CMA]) and comprehensive Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, whole-exon or whole-gene deletions/duplications are not detected. Novel SOX2 partner-factor domain mutation in a four-generation family. Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. For a review article see Julian et al [2017]. University of Washington, Seattle, Seattle (WA). Europe PMC is an archive of life sciences journal literature. An ocularist is a provider who can make prosthetic devices like artificial eyes and conformers. Variants listed in the table have been provided by the authors. What is the prognosis of a genetic condition? For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click Sox2 anophthalmia syndrome is an autosomal dominant inheritance. Chromosomal aberrations involving this region of chromosome 3 have also been found. Mol Vis. Inheritance was observed as de novo constitutive or de novo mosaic events, or, less frequently, from parents with constitutional duplications (see DECIPHER). Hum Mol Genet. There are early intervention services to help your child learn and support groups to help your family and your child succeed. recurrence of SOX2 anophthalmia syndrome: phenotypically normal mother with two An oculoplastic surgeon is a surgeon who has special training with the eyes, the eye sockets and the bones that make them up. GeneReviews(R) [Internet]. Mesial temporal heterotopia is highly assoc w/future epilepsy. SOX2-specific laboratory technical considerations. People with SOX2 anophthalmia syndrome are usually born without eyeballs (anophthalmia), although some individuals have small eyes (microphthalmia). Both conditions are rare, and can cause vision loss or blindness. Am J Med Genet A. 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. Note: Note: Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [Richards et al 2015]. Posted on June 29, 2022 SOX2 anophthalmia syndrome: In addition to having no eyes or small eyes, people with this syndrome may have seizures and problems with the brain. The N-terminal region is of unknown function and contains short polyglycine and polyalanine repeats. Data were extracted from full text case reports exclusively describing SOX2 disorder (n=38) using exact string matching. 16,17 Systemic associations included anophthalmia-plus syndrome, 19 Waardenburg-type ophthalmo-acromelic syndrome, 20 otocephaly, 16 limb body wall complex, 17 and holoprosencephaly. Both the globe (human eye) and the ocular tissue are missing from the orbit. SOX2 plays a critical role 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. Of the three, coloboma is the most common condition in the MAC spectrum, affecting 1 in 5000 newborns. Khler S, Carmody L, Vasilevsky N, Jacobsen JOB, Danis D, Gourdine JP, Gargano M, Harris NL, Matentzoglu N, McMurry JA, Osumi-Sutherland D, Cipriani V, Balhoff JP, Conlin T, Blau H, Baynam G, Palmer R, Gratian D, Dawkins H, Segal M, Jansen AC, Muaz A, Chang WH, Bergerson J, Laulederkind SJF, Yksel Z, Beltran S, Freeman AF, Sergouniotis PI, Durkin D, Storm AL, Hanauer M, Brudno M, Bello SM, Sincan M, Rageth K, Wheeler MT, Oegema R, Lourghi H, Della Rocca MG, Thompson R, Castellanos F, Priest J, Cunningham-Rundles C, Hegde A, Lovering RC, Hajek C, Olry A, Notarangelo L, Similuk M, Zhang XA, Gmez-Andrs D, Lochmller H, Dollfus H, Rosenzweig S, Marwaha S, Rath A, Sullivan K, Smith C, Milner JD, Leroux D, Boerkoel CF, Klion A, Carter MC, Groza T, Smedley D, Haendel MA, Mungall C, Robinson PN. Community vision services through early intervention or school district, Recurrent variant specifically assoc w/status dystonicus [. Being exposed to chemicals, like drugs or pesticides, during pregnancy. What are the different ways a genetic condition can be inherited? Hearing device can be helpful but no treatment is available for the eyeball malformations. If CMA does not detect a copy number variant, genome sequencing and/or exome sequencing may be used. Microphthalmia is a birth defect in which one or both eyes did not develop fully, so they are small. Zenteno JC, Gascon-Guzman G, Tovilla-Canales JL. Contrary to popular belief, AAC devices do not hinder verbal development of speech, but rather support optimal speech and language development. Martinez E, Madsen EC. For more information, see the GeneReviews Copyright Notice and Usage Brain MRI. . Note: There may not be clinical trials for this disorder. The diagnosis can be made based on observation. The term anophthalmia is often used interchangeably with severe microphthalmia because individuals with no visible eyeballs typically have some remaining eye tissue. 2006 Feb 23 [Updated 2020 Jul 30]. The information on this site should not be used as a substitute for professional medical care or advice. Sibs of a proband. To use the sharing features on this page, please enable JavaScript. These conditions may also occur with other eye conditions or medical problems elsewhere on the body. Kelberman D, de Castro SC, Huang S, Crolla JA, Palmer R, Gregory JW, Taylor D, Cavallo L, Faienza MF, Fischetto R, Achermann JC, Martinez-Barbera JP, Rizzoti K, Lovell-Badge R, Robinson IC, Gerrelli D, Dattani MT. Its a question of managing these conditions and any other conditions that might occur with them. Consider referral to urologist for cryptorchidism or other genital malformations. No further modifications are allowed. Cavallo L, Faienza MF, Fischetto R, Achermann JC, Martinez-Barbera JP, Rizzoti K, Unilateral microphthalmia is the term for when the condition affects only one eye. Incl motor, adaptive, cognitive, & speech/language eval, Eval for early intervention/ special education, Mobility, ADL, & need for adaptive devices, Need for ongoing PT (to improve gross motor skills) &/or OT (to improve fine motor skills). They also help with socket and face development and can help with cosmetic concerns. Genes associated with ocular manifestations frequently observed in SOX2 disorder (with or without nonocular comorbidities) are summarized in Table 3. Note: Testing of parental DNA may not detect all instances of somatic and germline mosaicism. SOX2 eye defects are usually bilateral, severe, and apparent at birth or on routine prenatal ultrasound examination. Taking medications that include isotretinoin (Accutane) or thalidomide during a pregnancy. Williamson KA, Yates TM, FitzPatrick DR. SOX2 Disorder. Epub 2007 May Each of the hypothetic explanations for the embryonic origin of the small or missing eyes associated with SOX2 pathogenic variants predicts a different spectrum of clinical phenotypes. HGNC; For those receiving IEP services, the public school district is required to provide services until age 21. 2007 Nov . 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. INTRODUCTION SOX2 anophthalmia syndrome is an autosomal "Anophthalmia is the absence of one or both eyes. 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. Mechanism of disease causation. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas comprehensive genomic testing does not. Anophthalmia presents as a small, bony orbit, malar prominence, reduced palpebral fissure, short eyelids, and a constricted mucosal socket. Identification of novel mutations and sequence variants in Spasticity, including diplegia, paraparesis, or quadriparesis was reported in 13 individuals. . Some babies are born with these conditions due to genetic changes. Vision and hearing consultants should be a part of the child's IEP team to support access to academic material. 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. Seizures were observed in 22 individuals. W/attention to brain/pituitary malformations, optic nerve/chiasm/tract. The following section deals with genetic sox2 anophthalmia syndrome life expectancy Isgho Votre ducation notre priorit 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. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. Anophthalmos, microphthalmos, and typical coloboma in the United Kingdom: a prospective study of incidence and risk. Mutations in the SOX2 gene prevent the production of functional SOX2 protein. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Dystonia may worsen & can show acute change to status dystonicus, which should be considered a medical emergency. Sisodiya SM, Ragge NK, Cavalleri GL, Hever A, Lorenz B, Schneider A, Williamson KA, Stevens JM, Free SL, Thompson PJ, van Heyningen V, Fitzpatrick DR. Role of SOX2 mutations in human hippocampal malformations and epilepsy. Schneider A, Young TL. PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Less frequent variants, esp those that alter residues adjacent to Tyr160, are also assoc w/severe phenotype. Babies with SOX2 anophthalmia syndrome may have seizures, brains problems, slow growth, developmental delays and learning disabilities. OMIM; Family history is consistent with autosomal dominant inheritance, including simplex cases (i.e., a single occurrence in a family). Feb 19. While both eyes are usually affected in SOX2 anophthalmia syndrome, one eye may be more affected than the other. Identification of novel mutations and sequence variants in the SOX2 and CHX10 genes in patients with anophthalmia/microphthalmia. Extension of the mutational and clinical spectrum of SOX2 related disorders: Description of six new cases and a novel association with suprasellar teratoma. 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.