Male A, Davies A, Bergbaum A, Keeling J, FitzPatrick D, Mackie Ogilvie C, Berg J. Delineation of an estimated 6.7 MB candidate interval for an anophthalmia gene at 3q26.33-q28 and description of the syndrome associated with visible chromosome deletions of this region. If the primary defect is in the mechanism of optic fissure closure, the predicted order of severity would be iris coloboma, choroidal/retinal coloboma, microphthalmia with coloboma or orbital cyst, and anophthalmia. If CMA does not detect a copy number variant, genome sequencing and/or exome sequencing may be used. In the US, developmental preschool through the local public school district 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. Without this Sox2 protein, the activity of genes that is important for the development of the eye is disrupted. Certain defects such as those of the heart, palate and esophagus can be surgically repaired. Intellectual ability is highly variable, ranging from normal to profound learning disability, with the majority having moderate learning disability. Inheritance was observed as de novo constitutive or de novo mosaic events, or, less frequently, from parents with constitutional duplications (see DECIPHER). Mechanism of disease causation. Genes and Databases for chromosome locus and protein. Anophthalmia - an overview | ScienceDirect Topics silobration vendor application 2022 - laoiscivildefence.org Feb 19. The absence of the eye will cause a small bony orbit, a constricted mucosal socket, short eyelids, reduced palpebral fissure SOX2 anophthalmia syndrome is estimated to affect 1 in 250,000 individuals. Conditions that are a result of problems with fetal development are sometimes called birth defects. For an introduction to comprehensive genomic testing click here. If a parent has a balanced structural chromosome rearrangement involving the 3q26.33 region, the risk to sibs is increased. of GeneReviews chapters for use in lab reports and clinic notes are a permitted The ontology structure describes the relationship of terms to each other [Khler et al 2019]. Schneider A, Bardakjian TM, Zhou J, Hughes N, Keep R, Dorsainville D, Kherani Hussenet T et al: 18268498: 2008: SOX2 is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest . The eyes are often absent or severely underdeveloped (anophthalmia), or they may be abnormally small (microphthalmia). Hearing aids may be helpful per audiologist/otolaryngologist. See our, URL of this page: https://medlineplus.gov/genetics/condition/sox2-anophthalmia-syndrome/. 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 . The most common genetic cause for anophthalmia is mutated SOX2gene. Familial recurrence of SOX2 anophthalmia syndrome: phenotypically normal mother with two affected daughters. These early intervention services will help babies learn to walk, talk and interact with others. Although normal eye development is possible in SOX2 disorder, all such individuals had extraocular defects. . Assess for sensorineural & conductive hearing loss. SOX2 anophthalmia syndrome - PubMed SOX2 anophthalmia syndrome: 12 new cases demonstrating broader To inform affected persons & their families re nature, MOI, & implications of, Referral to physiotherapist if evidence of motor impairment, Early referral to an experienced multidisciplinary team, Hormone replacement by pediatric endocrinologist, Hormone replacement prior to expected onset of puberty by pediatric endocrinologist, Standardized treatment w/ASM by experienced neurologist, Orthopedist/ physical medicine & rehab/ PT/OT incl stretching to help avoid contractures & falls. IJMS | Free Full-Text | SOX2 and SOX21 in Lung Epithelial 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. 15 A family history of anophthalmia was present in . All ages. How do people inherit SOX2 syndrome? Genetic Testing Registry: Anophthalmia/microphthalmia-esophageal atresia syndrome, National Organization for Rare Disorders (NORD). For issues to consider in interpretation of sequence analysis results, click here. Data and Statistics on Down Syndrome | CDC Bilateral anophthalmia and/or microphthalmia, Unilateral anophthalmia or microphthalmia, Genital abnormalities. What are the different ways a genetic condition can be inherited? 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]. National Library of Medicine. To date, 174 individuals from 157 families have been identified with SOX2 disorder [Williamson & FitzPatrick 2014, Gorman et al 2016, Dennert et al 2017, Blackburn et al 2018]. GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen.hgvs.org). BMP4 loss-of-function mutations in developmental eye disorders including SHORT syndrome. Bean LJH, Gripp KW, Amemiya A, editors. Most cases result from new mutations in the SOX2 gene and occur in people with no history of the disorder in their family. For a review article see Julian et al [2017]. Disclaimer, Developmental Delay/ Intellectual Disability Management Issues. 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). Always go to your appointments, even if you feel fine. As the lung develops, cells become specified and differentiate into the various cell lineages. Sox2 anophthalmia syndrome is an autosomal dominant inheritance. Deml B, Reis LM, Lemyre E, Clark RD, Kariminejad A, Semina EV. The features of this condition are present from birth. 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. 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. Erratum In: Hum Mol Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas comprehensive genomic testing does not. Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. GeneReviews chapters are owned by the University of Washington. sox2 anophthalmia syndrome life expectancy Ages 3-5 years. In 1960, on average, persons with Down syndrome lived to be about 10 years old. Its a specialized imaging test that may be helpful in evaluating for fetal congenital anomalies and associated complications. Chromosomal aberrations involving this region of chromosome 3 have also been found. Anophthalmia - Wikipedia Abstract Heterozygous, de novo, loss-of-function mutations in SOX2 have been shown to cause bilateral anophthalmia. 1. GeneReviews is not responsible for the information provided by other SOX2 Anophthalmia Syndrome | Encyclopedia MDPI SOX2 anophthalmia syndrome is estimated to affect 1 in 250,000 individuals. The term anophthalmia is often used interchangeably with severe microphthalmia because individuals with no visible eyeballs typically have some remaining eye tissue. 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). 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). Ptosis in childhood: A clinical sign of several disorders: Case series reports and literature review. Get useful, helpful and relevant health + wellness information, 9500 Euclid Avenue, Cleveland, Ohio 44195 |, Important Updates + Notice of Vendor Data Event. Microphthalmia, anophthalmia, coloboma (MAC): for patients People with SOX2 anophthalmia syndrome are usually born without eyeballs (anophthalmia), although some individuals have small eyes ( microphthalmia ). How do you know if your baby has anophthalmia or microphthalmia? (PDF) SOX2 Syndrome: A Case with Typical Clinical Profile - ResearchGate 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. 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. Select Features of SOX2 Disorder: Frequency of Human Phenotype Ontology (HPO) Terms. old fashion trends that died . 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. Delayed motor development was reported in the majority of affected children; the age of achieving independent walking ranged from 12 months to four years, although some individuals never achieve independent ambulation. Beyond that, private supportive therapies based on the affected individual's needs may be considered. 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. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. congenital absence of the eye or eyes. Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist. ethical issues that may arise or to substitute for consultation with a genetics 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. Medical Genetics: Mosaicism - Lucile Packard Children's Hospital About 10 percent to 15 percent of people with anophthalmia in both eyes have SOX2 syndrome. 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. While both eyes are usually affected in SOX2 anophthalmia syndrome, one eye may be more affected than the other. Recommended Evaluations Following Initial Diagnosis in Individuals with SOX2 Disorder, Treatment of Manifestations in Individuals with SOX2 Disorder. Schneider A, Bardakjian T, Reis LM, Tyler RC, Semina EV. Novel SOX2 mutations and genotype-phenotype correlation in anophthalmia and microphthalmia. Note on Table A, Locus-Specific Databases: See also the DECIPHER database. 2007 Nov . A/M is rare, but the exact incidence is unknown. [ Read summary ] Many factors can affect how long a person with Down syndrome lives. Keywords: Anopthalmia; microphthalmia; other disorders; quality of life. Dis. No further modifications are allowed. [3] Microphthalmia-associated transcription factor (MITF), located on chromosome 14q32, is associated with one form of isolated microphthalmia (MCOP1). There are early intervention services to help your child learn and support groups to help your family and your child succeed. When anophthalmia or microphthalmia is the only condition a baby has, it's called nonsyndromic or isolated. Lovell-Badge R, Robinson IC, Gerrelli D, Dattani MT. ), (https://www.marchofdimes.org/complications/anophthalmia-and-microphthalmia.aspx), (https://medlineplus.gov/genetics/condition/sox2-anophthalmia-syndrome/#references). 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. One of these individuals, who also had a dystonic movement disorder and unilateral strabismus as the only eye defect, had a 1.6- to 2-megabase (Mb) deletion encompassing SOX2 [Dennert et al 2017]. In 2007, on average, persons with Down syndrome lived to be about 47 years old. Embryology, Eye Malformations Article - StatPearls most nfl players by state per capita; press back chairs history; how to cut rubber backed carpet tiles; cape verdean tuna recipes. Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources. mutual life insurance companies list. Community hearing services through early intervention or school district, MRI, assessment of vision, ophthalmologic eval, Every 3-6 mos during childhood w/MRI only if change in clinical status, e.g., sudden change in light-dark or color perception, Follow-up eval w/ophthalmo-plastic surgeon. The lung originates from the ventral foregut and develops into an intricate branched structure of airways, alveoli, vessels and support tissue. Heterozygous, de novo, loss-of-function mutations in SOX2 have been shown to cause bilateral anophthalmia. The incidence of parental germline mosaicism in, The family history of some individuals diagnosed with, If a parent is affected and/or has the genetic alteration identified in the proband, the risk to the sibs of inheriting the genetic alteration is 50%. Sox2 anophthalmia syndromeis 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. For information on selection criteria, click here. Both conditions are rare, and can cause vision loss or blindness. Triple X syndrome. sox2 anophthalmia syndrome life expectancy. We do not endorse non-Cleveland Clinic products or services. 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. Extra-ocular anomalies are common. For those w/micropenis, refer to endocrinologist for consideration of eval for hypogonadotropic hypogonadism. Familial recurrence of SOX2 anophthalmia syndrome: Phenotypically GeneReviews [Internet]. Orphanet J Rare This syndrome causes a decrease in the production of sox2 protein which regulates the other gene's activities which bind to other regions of DNA. 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. University of Washington, Seattle, Seattle (WA). 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. Almost all SOX2 pathogenic variants reported to date appear to represent heterozygous loss of function; thus, it is difficult to draw genotype-phenotype correlations. (PDF) Case Report: Anophthalmia | Duong Dieu - Academia.edu 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. In the 174 individuals reported (114 individuals reviewed by Williamson & FitzPatrick [2014] plus 60 individuals reported subsequently), 76 (44%) had bilateral anophthalmia, 23 (13%) had anophthalmia with contralateral microphthalmia, and 20 (12%) had bilateral microphthalmia. Mutations in the SOX2 gene prevent the production of functional SOX2 protein. Approximately 60% of affected individuals have a de novo genetic alteration. For example, even in extreme microphthalmia, functional retinal tissue can give some light/dark perception with or without color perception. Dystonia and spasticity. Contact a health care provider if you have questions about your health. Gerth-Kahlert C, Williamson K, Ansari M, Rainger JK, Hingst V, Zimmermann T, Tech S, Guthoff RF, van Heyningen V, Fitzpatrick DR. Clinical and mutation analysis of 51 probands with anophthalmia and/or severe microphthalmia from a single center. It has been called also the SOX 2 anophthalmia syndrome 3 due to the frequent mutations and/or deletions found in the SOX2 gene. 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). 2008 Mar 24;14:583-92. 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 . The following descriptions are based on these key reports, together with all other published cases and the authors' unpublished data. 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. Mol Vis. 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 Severe genital but no major ocular anomalies in a female patient with the recurrent c.70del20 variant. Mesial temporal heterotopia is highly assoc w/future epilepsy. New GJA8 variants and phenotypes highlight its critical role in a broad spectrum of eye anomalies. Epub 2006 Mar 16. The SOX2 anophthalmia syndrome is emerging as a clinically recognizable disorder that has been identified in 10-15% of individuals with bilateral anophthalmia. noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright ( 1993-2023 University of 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. Dennert N, Engels H, Cremer K, Becker J, Wohlleber E, Albrecht B, Ehret JK, Ldecke HJ, Suri M, Carignani G, Renieri A, Kukuk GM, Wieland T, Andrieux J, Strom TM, Wieczorek D, Dieux-Coslier A, Zink AM. Ophthalmo-acromelic syndrome is a condition that results in malformations of the eyes, hands, and feet. The role of SOX2 in hypogonadotropic hypogonadism. Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel, and chromosomal microarray analysis [CMA]) and comprehensive Consider need for positioning & mobility devices & disability parking placard. Esophageal atresia or stenosis was reported in nine and three individuals, respectively. sox2 anophthalmia syndrome life expectancy. What is the prognosis of a genetic condition? Absence of a known family history does not preclude the diagnosis. This condition is caused by an extra X chromosome in each of a female's cells. People can be born with one or two small eyes (microphthalmia) or without one or both eyes (anophthalmia). Anophthalmos, microphthalmos, and typical coloboma in the United Kingdom: a prospective study of incidence and risk. 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. Two Cases of Anophthalmia and Quality Of Life - ResearchGate Seattle (WA): University of Washington, Seattle; 1993-2023. MRI stands for magnetic resonance imaging. SOX2 anophthalmia syndrome: In addition to having no eyes or small eyes, people with this syndrome may have seizures and problems with the brain. Note: There may not be clinical trials for this disorder. Treatment Depending upon the severity of malformations, life expectancy can be normal but some patients have died in the neonatal period. sox2 anophthalmia syndrome life expectancy Anophthalmia/Microphthalmia (A/M) may affect one eye with the other eye being normal, or both eyes, resulting in blindness. In . 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. i told him i miss him and he said aww; la porosidad es una propiedad extensiva o intensiva 2006 May 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. 2008;2(4-5):194-9. doi: 10.1159/000152035. In males, micropenis and cryptorchidism (often a manifestation of congenital hypogonadotropic hypogonadism) are common. It mostly happens in the. Anophthalmia is the absence of one or both eyes. SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions. 8 color. MRC Institute of Genetics and Molecular Medicine Depending upon the severity of malformations, life expectancy can be normal but some patients have died in the neonatal period. . 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. 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). Stark Z, Storen R, Bennetts B, Savarirayan R, Jamieson RV. Specific recommendations regarding type of therapy can be made by a developmental pediatrician. 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). 1. 2007 Nov 26;2:47. doi: 10.1186/1750-1172-2-47. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. Anophthalmos-. Selection and monitoring methods for xenotransplantation - US11424007B2 van Heyningen V, FitzPatrick DR. Mutations in SOX2 cause Abnormal development of these structures causes the signs and symptoms of SOX2 anophthalmia syndrome. The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy. Conformers: These are devices that fit into the eye socket to help your eye socket and face develop more typically. Assess axial & peripheral tone to advise on likely efficacy of antispasmodic medications & procedures. SOX2 (SRY (sex determining region Y)-box 2) Vision and hearing consultants should be a part of the child's IEP team to support access to academic material. Together they are the most common cause of childhood sight impairment registration in England and Wales (18.4% of children). 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. Seven children had apparently nonprogressive moderate sensorineural hearing loss requiring hearing aids. Data are compiled from the following standard references: gene from Two or more of these features need to be present for a clinical diagnosis only 30% of patients have all three. A congenital condition is one that you have when youre born. SOX2 anophthalmia syndrome is a rare disorder characterized by abnormal development of the eyes and other parts of the body. Genetic counseling is the process of providing individuals and families with Correcting refractive error is necessary to treat any sign of. What does it mean if a disorder seems to run in my family? HGNC; They often arise in conjunction with other ocular defects such as coloboma and orbital cyst. Br J GeneReviews staff has selected the following disease-specific and/or umbrella contact: ude.wu@tssamda. American Academy of Ophthalmology. In general, retina tissue that is present has some functional activity. 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. Ophthalmol. SOX2 anophthalmia syndrome: 12 new cases 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. People with SOX2 anophthalmia syndrome are usually born without eyeballs (anophthalmia), although some individuals have small eyes (microphthalmia). If you have it, your cornea doesnt reach 10 mm in diameter even when youre an adult. Septum pellucidum defects, cerebellar hypoplasia, hypothalamic hamartoma, arachnoid cyst, and sellar or suprasellar tumors are also reported in multiple individuals [Ragge et al 2005, Sisodiya et al 2006, Gerth-Kahlert et al 2013, Blackburn et al 2018]. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided. 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.