Trisomy (or “duplication”) of a particular region or regions of chromosome 13 is responsible for the symptoms and findings that characterize the disorder. Abnormalities of the genitals are also associated with Trisomy 13 Syndrome, including undescended testes (cryptorchidism) and an abnormally formed scrotum in affected males and underdeveloped ovaries and malformed uterus (bicornuate uterus) in affected females. When isolated, only spina bifida, holoprosencephaly, and agenesis of the corpus callosum were significantly associated with trisomy 13, anencephaly with trisomy 18, … 14. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site. Discussion: It is the first case where holoprosencephaly, proboscis and anophthalmia have been recognised in a foetus with matUPD14 and trisomy 13. HPE also occurs as a component of multiple malformation syndromes and in several chromosomal abnormalities, most commonly trisomy 13, trisomy 18, and triploidy. The diagnosis of Trisomy 13 Syndrome may be made or confirmed after birth (postnatally) by a thorough clinical evaluation, detection of characteristic physical findings, and chromosomal analysis. Array CGH confirmed trisomy 13 and molecular analysis recognised matUPD14 in chromosome 14 and region 14q12. There are several different types of holoprosencephaly. The treatment of Trisomy 13 Syndrome is directed toward the specific symptoms that are apparent in each individual. Am J Med Genet. Am J Med Genet. A chromosome analysis and gene testing is often performed. In addition, the eyebrows may be sparse or absent. Plastic reconstructive surgery of cleft lip and palate or other facial features may be needed if indicated. Am J Med Genet. Please note that NORD provides this information for the benefit of the rare disease community. Trisomy 13 accounts for up to 75% of cases of patients with holoprosencephaly (HPE)3 due to all chromosomal anomalies (including cryptic rearrangements). In cases in which only a percentage of cells contains the trisomy 13 abnormality (mosaicism), errors may also occur during cellular division after fertilization (mitosis). McKusick VA, ed. Neurological problems such as a small head (microcephaly), failure of the brain to divide into halves during gestati… These may include multiple cysts in the kidneys; abnormal union of the two kidneys at the base (horseshoe kidney); and/or swelling of the kidneys with urine due to blockage or narrowing of the ureters (hydronephrosis), which carry urine into the bladder. There is an increased risk for holoprosencephaly in infants born to diabetic mothers. Trisomy 13 Syndrome is a rare chromosomal disorder in which all or a portion of chromosome 13 appears three times (trisomy) rather than twice in cells of the body. NORD strives to open new assistance programs as funding allows. For more information, contact: Tracking Rare Incidence Syndromes (TRIS) project Phone: (618) 453-2311, Email: [email protected] Website: http://tris.siu.edu/. Although symptoms and findings are similar to those potentially associated with Trisomy 13 Syndrome, infants with this disorder do not have an extra chromosome 13 and their chromosomal studies appear normal. If we don't have a program for you now, please continue to check back with us. 1 The spectrum of severity of the defect ranges from the failure of the olfactory system to develop (arrhinencephaly) to failure of evagination and cleavage of the prosencephalon (cyclops). Holoprosencephaly (HPE) is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis. Lancet. Evidence suggests that this disorder may be inherited as an autosomal recessive trait. Investigators suggest that certain symptoms and findings associated with Trisomy 13 Syndrome may result from overexpression of developmentally important genes on chromosome 13. Some of these genes are SHH, SIX3, TGIF1, ZIC2, PTCH1, FOXH1, NODAL, CDON, FGF8, and GLI2. Dover, Mass: Blackwell Scientific Publications, Inc.; 1990:368-70. 1 Chromosomal analysis has been reported in some cases of … A supportive team approach for children with this disorder may be of benefit and may include physical therapy, medical, and/or social services. Associated symptoms and findings may vary in range and severity from case to case. Clin Dysmorphol. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site. 1993;47:405-09. Br J Radiol. Many infants are thought to be deaf, and profound mental retardation is usually present. Myelomeningocele is characterized by protrusion of a membranous sac containing a portion of the spinal cord, its meninges, and CSF through a defect in the spinal column. J Med Genet. 1993;53:810-16. Many babies do not survive past the first month or within the first year.1 Other symptoms include: 1. Approximately one-third of children born with holoprosencephaly have an abnormality of the chromosomes, which contain the genetic material (DNA). Pre-eclampsia and trisomy 13: a possible association. For example, the gene that regulates production of an enzyme known as esterase D (ESD) has been located on the long arm (q) of chromosome 13 (13q14.11). Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered. In addition, these characteristics were confirmed in real time by fetoscopy. Trisomy 13 with alobar holoprosencephaly. New York, NY: Oxford University Press; 1990:40-43, 576, 579. Lancet. However, in many affected infants and children, such abnormalities may include developmental delays, profound mental retardation, unusually small eyes (microphthalmia), an abnormal groove in the upper lip (cleft lip), incomplete closure of the roof of the mouth (cleft palate), undescended testes (cryptorchidism) in affected males, and extra (supernumerary) fingers and toes (polydactyly). Mutations in the gene encoding the Sonic Hedgehog protein, which is involved in the development of the central nervous system (CNS), can cause holoprosencephaly. Copyright ©2020 NORD - National Organization for Rare Disorders, Inc. All rights reserved. Copyright ©2020 NORD - National Organization for Rare Disorders, Inc. All rights reserved. The Tracking Rare Incidence Syndromes (TRIS) project is designed to raise awareness and provide support for families and professionals involved in the care of children and adults with rare trisomy conditions. Many infants with Trisomy 13 Syndrome fail to grow and gain weight at the expected rate (failure to thrive) and have severe feeding difficulties, diminished muscle tone (hypotonia), and episodes in which there is temporary cessation of spontaneous berathing (apnea). Such researchers suggest the possibility that a gene or genes on fetal chromosome 13 may influence the development of preeclampsia. Overexpression of esterase D in kidney from trisomy 13 fetuses. Natural history of trisomy 18 and trisomy 13: II. Growth, physical assessment, medical histories, survival, and recurrence risk. The embryology and implications of holoprosencephaly are described. In other children, holoprosencephaly is due to a change in a specific gene. It's also called trisomy 13. 3rd ed. The exact cause(s) of HPE are yet to be determined. Pseudotrisomy 13 syndrome in siblings. Other characteristics may include a short neck; loose skin folds over the back of the neck; and/or the presence of a benign lesion or birthmark consisting of abnormal clusters of blood vessels (capillary hemangiomas), most frequently on the center of the forehead. Ramos-Arroyo MA, et al. Amor DJ, et al. 1994;50:177-79. In some cases, other defects may be present involving the pulmonary artery and aorta, certain heart valves, and/or heart chambers. NORD strives to open new assistance programs as funding allows. In those with Trisomy 13 Syndrome, holoprosencephaly may result in various associated, midline facial defects, including closely set eyes (hypotelorism); an abnormal groove in the middle and side of the upper lip (median and lateral cleft lip); abnormalities of the nose; and/or other features. National Organization for Rare Disorders (NORD) 55 Kenosia Ave., Danbury CT 06810 • (203)744-0100. The severity and range of symptoms may depend on the length and location of the duplicated portion of the chromosome. Tuohy JF, et al. Abnormalities in the formation of the nose may also occur. Genetic HPE is associated with four genes and has been linked to seven additional chromosomal loci. These may include more than the normal number of fingers and/or toes (polydactyly); abnormal bending (flexion) and possible overlapping of fingers; and unusually rounded (hyperconvex) nails. Holoprosencephaly is classified into into 3 main subtypes based upon the severity of the malformation: lobar, semilobar, and alobar, and a fourth subtype, known as the middle interhemispheric (MIH) variant: Alobar holoprosencephaly is when there is a complete failure of the brain to divide into right and left hemispheres which results in the loss of midline structures … Pediatricians, neurologists, dentists, special education teachers, surgeons, therapists, psychologists, developmental pediatricians, and others must systematically and comprehensively plan the child’s treatment for holoprosencephaly. Children diagnosed with this disorder may have a small head (microcephaly), excessive fluid in the brain (hydrocephalus), facial abnormalities, tooth abnormalities (single central incisor), cleft lip and/or palate, epilepsy, and/or endocrine abnormalities. Investigators have also suggested a possible association between preeclampsia and Trisomy 13. Search for more papers by this author. The diagnosis of holoprosencephaly is usually made by MRI or CT of the brain. There are a number of other disorders, including other chromosomal syndromes, that may be characterized by symptoms and findings similar to those associated with Trisomy 13 Syndrome. Testing may also reveal unusual persistence of embryonic and/or fetal hemoglobin in the blood of newborns and infants with Trisomy 13 Syndrome. We have studied three chromosomally normal patients with multiple anomalies that include holoprosencephaly and caudal dysplasia. Clin Obstet Gynecol. Gorlin RJ, et al., eds. Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. 1994;49:175-88. The preterm newborn lived only 5 hours, and died because of severe respiratory failure. Chromosomal studies performed on such samples may reveal the presence of an extra chromosome 13. Smith’s Recognizable Patterns of Human Malformation. Buyse ML. Further delineation of pseudotrisomy 13 syndrome: a case without polydactyly. 1987;2:425-27. To search for patient organizations and other pages related to this topic, use the Advanced Search function at the top right corner of the page. cri du chat syndrome involves deletion of which chromosome? Other treatments can be instituted as appropriate. For infants diagnosed with the syndrome, careful monitoring and various specialized tests may be conducted to ensure early detection and appropriate management of conditions potentially associated with Trisomy 13 Syndrome. NORD gratefully acknowledges Jeffrey E. Ming, MD, PhD, Division of Human Genetics, The Children's Hospital of Philadelphia, for assistance in the preparation of this report. There is no treatment for holoprosencephaly and the prognosis for individuals with the disorder is poor. (The pulmonary artery carries oxygen-depleted blood from the right ventricle to the lungs, where the exchange of oxygen and carbon dioxide occurs. Holoprosencephaly (HPE) is the failure of the prosencephalon, or forebrain, to develop normally. Affected infants typically are unusually small and have feeding difficulties. 1994;49:189-94. GeneReviews [Internet]. In some cases, other abnormalities may also be present. A neurologist should also be involved in the child’s care and can guide treatment for seizures if they are present. Holoprosencephaly affects males and females in equal numbers before birth and has been reported in many ethnic groups. However, balanced translocations are sometimes associated with a higher risk of abnormal chromosomal development in the carrier’s offspring. Translocations occur when regions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. The two halves of the brain are completely fused, instead of – as in healthy people – connected only over a small part. In addition, the heart may be located in the right side of the chest, instead of its normal location in the left side of the chest (dextrocardia). The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Seattle (WA): University of Washington, Seattle; 1993-2018. Patau K, et al. (For further information on such disorders, choose the name of the specific disorder in question or use “chromosome” as your search term in the Rare Disease Database.). Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright. 5th ed. When examined as a series, the duplications (trisomy 13, trisomy 13pter → q14) and deletions (deletion 13q12 → qter, deletion 13q31 → qter, ring 13 with deletion 13q14 → qter) exclude deletion or duplication of single chromosome 13 bands as the cause for holoprosencephaly. Newborns born with Patau syndrome often have physical abnormalities or intellectual issues. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1530/ Accessed March 15, 2018. However, for most children, no known intrauterine exposure is identified that is causally related to holoprosencephaly in that child. Eur J Obstet Gynecol Reprod Biol. Am J Med Genet C Semin Med Genet. Trisomy 13 Syndrome is also frequently characterized by variable degrees of holoprosencephaly, a condition in which the forebrain fails to divide properly during embryonic development. Philadelphia, Pa: W.B. Rodriguez JI, et al. Other important findings associated with trisomy 13 include an abnormal midface with hypotelorism, cleft lip or palate, and even cyclopia (see Chapter 14) (Figure 129-2). Intellectual disability is associated with HPE and seizures are often present. Evidence suggests that the risk of such errors may increase with advanced parental age. Evidence suggests that approximately one percent of all recognized miscarriages occur in association with Trisomy 13 Syndrome. Birth Defects Encyclopedia. Psychomotor development. NORD is not a medical provider or health care facility and thus can neither diagnose any disease or disorder nor endorse or recommend any specific medical treatments. Chromosomes are found in the nucleus of all body cells. The heels of the feet may be abnormally prominent. In addition, in some cases, additional features may include abnormal tone of voluntary (skeletal) muscles; absence of the band of nerve fibers that joins the two hemispheres of the brain (agenesis of the corpus callosum); underdevelopment of the cerebellum (cerebellar hypoplasia); hydrocephalus; and/or myelomeningocele. 1991;39:332-35, 336-37. Deformed feet, known as rocker-bottom feet 3. Am J Hum Genet. 15. screening for aneuploid pregnancies is routinely performed @ ___ weeks of gestation. Br J Obstet Gynaecol. Relatives of a child with holoprosencephaly may have an increased risk of having a child with holoprosencephaly, and this should be assessed and discussed by the child’s physicians, especially the neurologist and/or clinical geneticist. Levey EB, Stashinko E, Clegg NJ, Delgado MR. Management of children with holoprosencephaly. In other children, holoprosencephaly is due to a change in a specific gene. In infants with PDA, the channel that is present between the pulmonary artery and the aorta during fetal development fails to close after birth. In addition, Trisomy 13 Syndrome may be associated with abnormal skin ridge patterns (dermatoglyphics), including a single deep crease across the palms of the hands (simian crease). Some children will have an identifiable genetic cause of holoprosencephaly. In addition, those with trisomy 13 mosaicism typically have less severe symptoms; however, in such cases, disease manifestations may be extremely variable, ranging from near normal to the full spectrum of malformations. Cohen MM, et al. An endocrinology evaluation should be performed to assess for pituitary abnormalities. Holoprosencephaly, polydactyly and normal chromosomes: pseudo‐trisomy 13? Despite the above understanding of the causes of holoprosencephaly, the exact cause of the condition is not identified for many individuals. 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