DOCSLIB.ORG

A Common Cause for Phelan-Mcdermid Syndrome and Neurofibromatosis Type 2: One Ring to Bind Them Ariel M

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Common Cause for Phelan-Mcdermid Syndrome and Neurofibromatosis Type 2: One Ring to Bind Them Ariel M RESIDENT & FELLOW SECTION Clinical Reasoning: Section Editor A common cause for Phelan-McDermid John J. Millichap, MD syndrome and neurofibromatosis type 2 One ring to bind them Ariel M. Lyons-Warren, SECTION 1 her mother reported loss of previously mastered MD, PhD An 8-year-old girl with mild dysmorphic features pre- vocabulary and struggles with fine motor skills such Sau Wai Cheung, PhD sented for evaluation of developmental delay and star- as buttoning. She also noted repetitive movements, J. Lloyd Holder Jr., MD, ing spells. She had been born late preterm and spent 1 obsessive behaviors, and hand flapping. PhD month in the neonatal intensive care unit. She was Question for consideration: generally healthy other than her developmental delay, which improved somewhat with physical, occupa- 1. What is the initial evaluation for a child with Correspondence to tional, and speech therapy. At the first clinic visit, developmental delay? Dr. Holder: [email protected] GO TO SECTION 2 From Baylor College of Medicine, Houston, TX. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. © 2017 American Academy of Neurology e205 ª 2017 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. SECTION 2 it increases to 5% in specific populations with other A total of 1%–3% of children younger than 5 are key clinical features. Therefore, routine screening is diagnosed with global developmental delay. The dif- not recommended.1 ferential diagnosis is broad and includes genetic, Our patient’s initial evaluation included an MRI structural, and metabolic causes.1 Initial evaluation brain that was unremarkable and a karyotype that should include neuroimaging, with MRI being pref- revealed a ring chromosome 22 including a terminal erable to CT. MRI brain will identify an abnormality deletion of the long arm. A ring chromosome is such as a malformation, atrophy, white matter dis- when the p and q arms of the chromosome fuse ease, demyelination, or injury in 48%–92% of chil- together and often occurs due to deletion of one dren with developmental delay.1 Evaluation should arm. Subsequent high-resolution karyotype with also include genetic testing such as karyotype, array subtelomeric fluorescent in situ hybridization anal- comparative genomic hybridization (aCGH), gene- ysis confirmed the diagnosis (figure, A) and demon- specific testing, and whole exome sequencing strated a double-sized ring chromosome 22 in 15% (WES).2 aCGH is now often considered the first- of cells. In order to better define the size of the line genetic test because it will identify an etiology in deletion, a high-resolution aCGH was performed, up to 20% of individuals with developmental delay which identified a 1.036-Mb deletion in the subte- through detection of genomic deletions and dupli- lomeric region of the long arm of chromosome 22 cations. In contrast, the diagnostic yield for karyo- involving 20 genes including SHANK3, consistent type is less than 10%. Therefore, while karyotype with the diagnosis of Phelan-McDermid syndrome will identify chromosomal abnormalities such as (PMS) (figure, B and C). To complete the evalua- Down syndrome, Turner syndrome, or large geno- tion, the patient was assessed with an Autism mic deletions, it is now frequently omitted in the Diagnostic Observation Schedule and met criteria evaluation of the developmentally delayed child. for autism. Single gene, gene panel, or WES is subsequently After receiving the diagnosis, the patient was lost ordered if clinically indicated. WES is ordered to to follow-up for several years. At age 16, the family evaluate for de novo mutations in previously identi- noted a change in the patient’s personality. She pre- fied developmental genes when there are no clinical viously related well with other children and was features pointing towards a specific syndrome. Nota- described as sweet and kind. Her parents expressed bly, some complex genomic abnormalities such as concern for new episodes of unprovoked anger. Her ring chromosomes are not detected by aCGH, gene family also noted the development of painless growths testing, or WES. Therefore, children with terminal on both arms, most predominant on the left arm and chromosome deletions should be evaluated for a ring wrist. chromosome by karyotype. Questions for consideration: EEG is not indicated for routine evaluation of developmental delay unless the child exhibits regres- 1. What is the evaluation for behavioral regression in sion or seizures.2 a child with developmental delay? Routine screening for metabolic causes of global 2. How do the growths on the patient’s arm relate to developmental delay has a yield of only 1%, although her other signs and symptoms? GO TO SECTION 3 e206 Neurology 89 October 24, 2017 ª 2017 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. Figure Genetic and neuroimaging evaluation (A) Fluorescent in situ hybridization analysis depicts a normal chromosome 22 with Cosmid probe n85a3 of the SHANK3 gene in red and the control probe in green, and a ring chromosome with only green signal indicating the deletion of the SHANK3 gene at band 22q13.3 (red arrow). (B) High-resolution array comparative genomic hybridization shows all the oligo probes for chromosome 22 with a copy number loss of chromosome band 22q13.3 of 1.036 Mb (depicted as red circles). (C) Chromosome 22 ideogram shows the relative locations of SHANK3 and NF2. (D) Axial T1 postcontrast MRI brain. Red arrow points to bulky lobular, enhancing mass extending from the right cerebellopontine angle to the right internal auditory canal, consistent with a schwannoma. (E) Axial T1 postcontrast MRI spine with right lumbar paraspinal enhancing focus just medial to the right psoas muscle concerning for a small schwannoma. Neurology 89 October 24, 2017 e207 ª 2017 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. SECTION 3 as more than one-quarter of children will have renal In a child with developmental delay, frustration abnormalities ranging from reflux to absent kidneys. related to communication difficulties from impaired Individuals with PMS may also have developmental hearing or speech delay can manifest as aggression. structural brain abnormalities, including delayed New-onset seizure activity can also manifest as behav- myelination, thin corpus callosum, and arachnoid ior changes such as postictal agitation or irritability cysts. Finally, children with PMS can have sleep related to poor sleep following nocturnal seizures. abnormalities, including bedtime resistance, delayed Therefore, MRI brain, EEG, and audiology testing onset, sleep anxiety, parasomnias, sleep-disordered were ordered for this patient. breathing, and daytime sleepiness.3,4 Brain MRI revealed a large, enhancing right cere- Patients with PMS can have variable phenotype bellopontine angle to internal auditory canal vestibu- possibly related to size of their deletion on the long lar schwannoma (figure, D) and a punctate arm of chromosome 22.5 The majority of neurologic contralateral vestibular schwannoma that were not features, however, are believed to be due to haploin- present on the prior brain MRI brain at 8 years of sufficiency of the SHANK3 gene.6 The SHANK3 age. Based on these findings, MRI spine was also protein is enriched in the postsynaptic density of ordered and identified enhancing foci in multiple excitatory synapses. Along with other members of paraspinal areas, which were concerning for schwan- the SHANK protein family, SHANK3 is believed nomas (figure, E). EEG revealed a focus of sharp to play an important role in synaptogenesis, synapse transients over the left temporal region suggestive of maintenance, and synapse plasticity.6 an epileptogenic focus. The patient subsequently had NF2 is diagnosed using the Manchester criteria7: an event concerning for seizure in which she was • Bilateral vestibular schwannomas or staring and nonresponsive and then fell to the • Unilateral vestibular schwannoma and at least 2 ground. Audiology testing was not able to establish other features including meningioma, glioma, hearing sensitivity due to the patient’s inability to schwannoma, or juvenile posterior lenticular complete the task. However, crossed acoustic reflexes opacities were absent, suggesting impairment of the auditory nerve. The hallmark feature is bilateral vestibular Given the presence of bilateral vestibular as well as schwannomas. However, additional criteria allow spinal schwannomas, the growths on her arms were for the diagnosis in a patient with at least 2 meningi- likely peripheral schwannomas. The patient was omas and unilateral vestibular schwannoma or at least referred to oncology for further evaluation. She was 2 meningiomas and 2 of the other features including determined to meet criteria for neurofibromatosis glioma, neurofibroma, schwannoma, and cataract.7 type 2 (NF2). Comprehensive auditory evaluation Although schwannomas are benign, they can cause was difficult to obtain secondary to the patient’s intel- symptoms ranging from hearing loss to brainstem lectual disability. She was evaluated by neurosurgery, compression and are therefore usually monitored with who did not recommend surgical intervention as serial imaging.8 These symptoms are caused by dis- hearing was intact to voice. She was treated with ruption of the NF2 gene on chromosome 22 (figure, bevacizumab with significant
Load more

Recommended publications
  • Cellular and Synaptic Network Defects in Autism
    Cellular and synaptic network defects in autism The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Peca, Joao, and Guoping Feng. “Cellular and Synaptic Network Defects in Autism.” Current Opinion in Neurobiology 22, no. 5 (October 2012): 866–872. As Published http://dx.doi.org/10.1016/j.conb.2012.02.015 Publisher Elsevier Version Author's final manuscript Citable link http://hdl.handle.net/1721.1/102179 Terms of Use Creative Commons Attribution-Noncommercial-NoDerivatives Detailed Terms http://creativecommons.org/licenses/by-nc-nd/4.0/ NIH Public Access Author Manuscript Curr Opin Neurobiol. Author manuscript; available in PMC 2013 October 01. Published in final edited form as: Curr Opin Neurobiol. 2012 October ; 22(5): 866–872. doi:10.1016/j.conb.2012.02.015. Cellular and synaptic network defects in autism João Peça1 and Guoping Feng1,2 $watermark-text1McGovern $watermark-text Institute $watermark-text for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA 2Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02142, USA Abstract Many candidate genes are now thought to confer susceptibility to autism spectrum disorder (ASD). Here we review four interrelated complexes, each composed of multiple families of genes that functionally coalesce on common cellular pathways. We illustrate a common thread in the organization of glutamatergic synapses and suggest a link between genes involved in Tuberous Sclerosis Complex, Fragile X syndrome, Angelman syndrome and several synaptic ASD candidate genes. When viewed in this context, progress in deciphering the molecular architecture of cellular protein-protein interactions together with the unraveling of synaptic dysfunction in neural networks may prove pivotal to advancing our understanding of ASDs.
    [Show full text]
  • Klinefelter, Turner & Down Syndrome
    Klinefelter, Turner & Down Syndrome A brief discussion of gamete forma2on, Mitosis and Meiosis: h7ps://www.youtube.com/watch?v=zGVBAHAsjJM Non-disjunction in Meiosis: • Nondisjunction "not coming apart" is the failure of a chromosome pair to separate properly during meiosis 1, or of two chromatids of a chromosome to separate properly during meiosis 2 or mitosis. • Can effect each pair. • Not a rare event. • As a result, one daughter cell has two chromosomes or two chromatids and the other has none • The result of this error is ANEUPLOIDY. 4 haploid gametes 2 gametes with diploid 2 gametes with haploid number of x and 2 lacking number of X chromosome, 1 x chromosome gamete with diploid number of X chromosome, and 1 gamete lacking X chromosome MEIOSIS MITOSIS Nondisjunc2on at meiosis 1 = All gametes will be abnormal Nondisjunc2on at meiosis 2 = Half of the gametes are normal (%50 normal and %50 abnormal) Down’s Syndrome • Karyotype: 47, XY, +21 Three copies of chromosome 21 (21 trisomy) • The incidence of trisomy 21 rises sharply with increasing maternal age (above 37), but Down syndrome can also be the result of nondisjunction of the father's chromosome 21 (%15 of cases) • A small proportion of cases is mosaic* and probably arise from a non-disjunction event in early zygotic division. *“Mosaicism, used to describe the presence of more than one type of cells in a person. For example, when a baby is born with Down syndrome, the doctor will take a blood sample to perform a chromosome study. Typically, 20 different cells are analyzed.
    [Show full text]
  • Detection of Turner Syndrome by Quantitative PCR of SHOX and VAMP7 Genes
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Repositorio Academico Digital UANL GENETIC TESTING AND MOLECULAR BIOMARKERS ORIGINAL ARTICLES Volume 19, Number 2, 2015 ª Mary Ann Liebert, Inc. Pp. 1–5 DOI: 10.1089/gtmb.2014.0236 Detection of Turner Syndrome by Quantitative PCR of SHOX and VAMP7 Genes Marisol Ibarra-Ramı´rez,1 Michelle de Jesu´s Zamudio-Osuna,1 Luis Daniel Campos-Acevedo,1 Hugo Leonid Gallardo-Blanco,1 Ricardo Martin Cerda-Flores,2 Ira´m Pablo Rodrı´guez-Sa´nchez,1 and Laura Elia Martı´nez-de-Villarreal1 Turner Syndrome (TS) is an unfavorable genetic condition with a prevalence of 1:2500 in newborn girls. Prompt and effective diagnosis is very important to appropriately monitor the comorbidities. The aim of the present study was to propose a feasible and practical molecular diagnostic tool for newborn screening by quantifying the gene dosage of the SHOX, VAMP7, XIST, UBA1, and SRY genes by quantitative polymerase chain reaction (qPCR) in individuals with a diagnosis of complete X monosomy, as well as those with TS variants, and then compare the results to controls without chromosomal abnormalities. According to our results, the most useful markers for these chromosomal variants were the genes found in the pseudoautosomic regions 1 and 2 (PAR1 and PAR2), because differences in gene dosage (relative quantification) between groups were more evident in SHOX and VAMP7 gene expression. Therefore, we conclude that these markers are useful for early detection in aneuploidies involving sex chromosomes. Introduction Guidelines of the American College of Endocrinology for the management of patients with TS emphasize the benefit of urner syndrome (TS) affects 1 in 2500/3000 live- early detection through newborn screening methods (Bondy Tborn girls and is characterized by short stature, gonadal et al., 2007).
    [Show full text]
  • 22Q13.3 Deletion Syndrome
    22q13.3 deletion syndrome Description 22q13.3 deletion syndrome, which is also known as Phelan-McDermid syndrome, is a disorder caused by the loss of a small piece of chromosome 22. The deletion occurs near the end of the chromosome at a location designated q13.3. The features of 22q13.3 deletion syndrome vary widely and involve many parts of the body. Characteristic signs and symptoms include developmental delay, moderate to profound intellectual disability, decreased muscle tone (hypotonia), and absent or delayed speech. Some people with this condition have autism or autistic-like behavior that affects communication and social interaction, such as poor eye contact, sensitivity to touch, and aggressive behaviors. They may also chew on non-food items such as clothing. Less frequently, people with this condition have seizures or lose skills they had already acquired (developmental regression). Individuals with 22q13.3 deletion syndrome tend to have a decreased sensitivity to pain. Many also have a reduced ability to sweat, which can lead to a greater risk of overheating and dehydration. Some people with this condition have episodes of frequent vomiting and nausea (cyclic vomiting) and backflow of stomach acids into the esophagus (gastroesophageal reflux). People with 22q13.3 deletion syndrome typically have distinctive facial features, including a long, narrow head; prominent ears; a pointed chin; droopy eyelids (ptosis); and deep-set eyes. Other physical features seen with this condition include large and fleshy hands and/or feet, a fusion of the second and third toes (syndactyly), and small or abnormal toenails. Some affected individuals have rapid (accelerated) growth.
    [Show full text]
  • Turner Syndrome (TS) Is a Genetic Disease That Affects About Physical Signs of TS May Include: 1 in Every 2,500 Female Live Births
    Notes: A Guide for Caregivers For easily accessible answers, education, and support, visit Nutropin.com or call 1-866-NUTROPIN (1-866-688-7674). 18 19 of patients with Your healthcare team is your primary source Turner Syndrome of information about your child’s treatment. Please see the accompanying full Prescribing Information, including Instructions for Use, and additional Important Safety Information througout and on pages 16-18. Models used for illustrative purposes only. Nutropin, Nutropin AQ, and NuSpin are registered trademarks, Nutropin GPS is a trademark, and NuAccess is a service mark of Genentech, Inc. © 2020 Genentech USA, Inc., 1 DNA Way, So. San Francisco, CA 94080 M-US-00005837(v1.0) 06/20 FPO Understanding Turner Syndrome What is Turner Syndrome? Turner Syndrome (TS) is a genetic disease that affects about Physical signs of TS may include: 1 in every 2,500 female live births. TS occurs when one • Short stature of a girl’s two X chromosomes is absent or incomplete. • Webbing of the neck Chromosomes are found in all cells of the human body. They contain the genes that determine the characteristics of a • Low-set, rotated ears person such as the color of hair or eyes. Every person has • Arms that turn out slightly at the elbows 22 pairs of chromosomes containing these characteristics, • Low hairline at the back of the head and one pair of sex chromosomes. • A high, arched palate in the mouth Normally cells in a female’s body contain two “X” chromosomes Biological signs of TS may include: (Fig. 1). • Underdevelopment of the ovaries In girls with TS, part or • Not reaching sexual maturity or starting all of one X chromosome a menstrual period (Fig.
    [Show full text]
  • Oocyte Cryopreservation for Fertility Preservation in Postpubertal Female Children at Risk for Premature Ovarian Failure Due To
    Original Study Oocyte Cryopreservation for Fertility Preservation in Postpubertal Female Children at Risk for Premature Ovarian Failure Due to Accelerated Follicle Loss in Turner Syndrome or Cancer Treatments K. Oktay MD 1,2,*, G. Bedoschi MD 1,2 1 Innovation Institute for Fertility Preservation and IVF, New York, NY 2 Laboratory of Molecular Reproduction and Fertility Preservation, Obstetrics and Gynecology, New York Medical College, Valhalla, NY abstract Objective: To preliminarily study the feasibility of oocyte cryopreservation in postpubertal girls aged between 13 and 15 years who were at risk for premature ovarian failure due to the accelerated follicle loss associated with Turner syndrome or cancer treatments. Design: Retrospective cohort and review of literature. Setting: Academic fertility preservation unit. Participants: Three girls diagnosed with Turner syndrome, 1 girl diagnosed with germ-cell tumor. and 1 girl diagnosed with lymphoblastic leukemia. Interventions: Assessment of ovarian reserve, ovarian stimulation, oocyte retrieval, in vitro maturation, and mature oocyte cryopreservation. Main Outcome Measure: Response to ovarian stimulation, number of mature oocytes cryopreserved and complications, if any. Results: Mean anti-mullerian€ hormone, baseline follical stimulating hormone, estradiol, and antral follicle counts were 1.30 Æ 0.39, 6.08 Æ 2.63, 41.39 Æ 24.68, 8.0 Æ 3.2; respectively. In Turner girls the ovarian reserve assessment indicated already diminished ovarian reserve. Ovarian stimulation and oocyte cryopreservation was successfully performed in all female children referred for fertility preser- vation. A range of 4-11 mature oocytes (mean 8.1 Æ 3.4) was cryopreserved without any complications. All girls tolerated the procedure well.
    [Show full text]
  • Turner Syndrome
    TURNER SYNDROME What is it? Turner syndrome (TS) is a condition only affecting females as a result of an X chromosome abnormality. TS occurs in approximately 1 in 2,500 newborn females. While one X chromosome is normal, the other female X chromosome is missing or altered. TS is characterized by a variety of medical and developmental problems but the most consistent features affect bone development and growth resulting in short stature and lack of ovarian development. Diagnosis can be made prenatally or in early childhood but over 1/3 of girls diagnosed are diagnosed in mid-childhood or adolescence. A blood test can confirm suspicion of the syndrome. The long term health outcomes are improved with an earlier diagnosis. What are the symptoms or complications? Diagnosis can be made prenatally or during early childhood years. However, over 1/3 of diagnoses occur during adolescence. A blood test can confirm suspicion of the syndrome. Signs and symptoms may be subtle and develop slow over time, or they may be significant. They can occur in varying degrees based on the individual's genetic makeup. Short stature Scoliosis Swelling of hands and feet Recurrent ear infections that may lead to hearing problems Lack of spontaneous puberty Webbed neck Kidney problems e.g. UTI’s Droopy eyelids Heart issues e.g. congenital defects Strabismus Type II Diabetes Low set ears and hairline Hypertension Poor vision Thyroid disease Infertility Lack of stamina A child with TS will not only face medical problems but also learning disabilities. Students with TS often have a cognitive profile that includes normal intelligence and verbal capabilities but weaknesses in the areas of visual–spatial, executive, and social cognitive function.
    [Show full text]
  • Dr. Fern Tsien, Dept. of Genetics, LSUHSC, NO, LA Down Syndrome
    COMMON TYPES OF CHROMOSOME ABNORMALITIES Dr. Fern Tsien, Dept. of Genetics, LSUHSC, NO, LA A. Trisomy: instead of having the normal two copies of each chromosome, an individual has three of a particular chromosome. Which chromosome is trisomic determines the type and severity of the disorder. Down syndrome or Trisomy 21, is the most common trisomy, occurring in 1 per 800 births (about 3,400) a year in the United States. It is one of the most common genetic birth defects. According to the National Down Syndrome Society, there are more than 400,000 individuals with Down syndrome in the United States. Patients with Down syndrome have three copies of their 21 chromosomes instead of the normal two. The major clinical features of Down syndrome patients include low muscle tone, small stature, an upward slant to the eyes, a single deep crease across the center of the palm, mental retardation, and physical abnormalities, including heart and intestinal defects, and increased risk of leukemia. Every person with Down syndrome is a unique individual and may possess these characteristics to different degrees. Down syndrome patients Karyotype of a male patient with trisomy 21 What are the causes of Down syndrome? • 95% of all Down syndrome patients have a trisomy due to nondisjunction before fertilization • 1-2% have a mosaic karyotype due to nondisjunction after fertilization • 3-4% are due to a translocation 1. Nondisjunction refers to the failure of chromosomes to separate during cell division in the formation of the egg, sperm, or the fetus, causing an abnormal number of chromosomes. As a result, the baby may have an extra chromosome (trisomy).
    [Show full text]
  • Rare Double Aneuploidy in Down Syndrome (Down- Klinefelter Syndrome)
    Research Article Journal of Molecular and Genetic Volume 14:2, 2020 DOI: 10.37421/jmgm.2020.14.444 Medicine ISSN: 1747-0862 Open Access Rare Double Aneuploidy in Down Syndrome (Down- Klinefelter Syndrome) Al-Buali Majed J1*, Al-Nahwi Fawatim A2, Al-Nowaiser Naziha A2, Al-Ali Rhaya A2, Al-Khamis Abdullah H2 and Al-Bahrani Hassan M2 1Deputy Chairman of Medical Genetic Unite, Pediatrics Department, Maternity Children Hospital Al-hassa, Hofuf, Saudi Arabia 2Pediatrics Resident, Pediatrics Department, Maternity Children Hospital Alhassa, Hofuf, Saudi Arabia Abstract Background: The chromosomal aneuploidy described as Cytogenetic condition characterized by abnormality in numbers of the chromosome. Aneuploid patient either trisomy or monosomy, can occur in both sex chromosomes as well as autosome chromosomes. However, double aneuploidies involving both sex and autosome chromosomes relatively a rare phenomenon. In present study, we reported a double aneuploidy (Down-Klinefelter syndrome) in infant from Saudi Arabia. Materials and Methods: In the present investigation, chromosomal analysis (standard chromosomal karyotyping) and fluorescence in situ hybridization (FISH) were performed according to the standard protocols. Results: Here, we report a single affected individual (boy) having Saudi origin, suffering from double chromosomal aneuploidy. The main presenting complaint is the obvious dysmorphic features suggesting Down syndrome. Chromosomal analysis and FISH revealed 48,XXY,+21, show the presence of three copies of chromosome 21, two copies of X chromosome and one copy of Y chromosome chromosomes. Conclusion: Patients with Down syndrome must be tested for other associated sex chromosome aneuploidies. Hence, proper diagnosis is needed for proper management and the cytogenetic tests should be performed as the first diagnostic approach.
    [Show full text]
  • Down-Syndrome.Pdf
    Down syndrome Description Down syndrome is a chromosomal condition that is associated with intellectual disability, a characteristic facial appearance, and weak muscle tone (hypotonia) in infancy. All affected individuals experience cognitive delays, but the intellectual disability is usually mild to moderate. People with Down syndrome often have a characteristic facial appearance that includes a flattened appearance to the face, outside corners of the eyes that point upward ( upslanting palpebral fissures), small ears, a short neck, and a tongue that tends to stick out of the mouth. Affected individuals may have a variety of birth defects. Many people with Down syndrome have small hands and feet and a single crease across the palms of the hands. About half of all affected children are born with a heart defect. Digestive abnormalities, such as a blockage of the intestine, are less common. Individuals with Down syndrome have an increased risk of developing several medical conditions. These include gastroesophageal reflux, which is a backflow of acidic stomach contents into the esophagus, and celiac disease, which is an intolerance of a wheat protein called gluten. About 15 percent of people with Down syndrome have an underactive thyroid gland (hypothyroidism). The thyroid gland is a butterfly-shaped organ in the lower neck that produces hormones. Individuals with Down syndrome also have an increased risk of hearing and vision problems. Additionally, a small percentage of children with Down syndrome develop cancer of blood-forming cells (leukemia). Delayed development and behavioral problems are often reported in children with Down syndrome. Affected individuals can have growth problems and their speech and language develop later and more slowly than in children without Down syndrome.
    [Show full text]
  • Double Aneuploidy in Down Syndrome
    Chapter 6 Double Aneuploidy in Down Syndrome Fatma Soylemez Additional information is available at the end of the chapter http://dx.doi.org/10.5772/60438 Abstract Aneuploidy is the second most important category of chromosome mutations relat‐ ing to abnormal chromosome number. It generally arises by nondisjunction at ei‐ ther the first or second meiotic division. However, the existence of two chromosomal abnormalities involving both autosomal and sex chromosomes in the same individual is relatively a rare phenomenon. The underlying mechanism in‐ volved in the formation of double aneuploidy is not well understood. Parental ori‐ gin is studied only in a small number of cases and both nondisjunctions occurring in a single parent is an extremely rare event. This chapter reviews the characteristics of double aneuploidies in Down syndrome have been discussed in the light of the published reports. Keywords: Double aneuploidy, Down Syndrome, Klinefelter Syndrome, Chromo‐ some abnormalities 1. Introduction With the discovery in 1956 that the correct chromosome number in humans is 46, the new area of clinical cytogenetic began its rapid growth. Several major chromosomal syndromes with altered numbers of chromosomes were reported, such as Down syndrome (trisomy 21), Turner syndrome (45,X) and Klinefelter syndrome (47,XXY). Since then it has been well established that chromosome abnormalities contribute significantly to genetic disease resulting in reproductive loss, infertility, stillbirths, congenital anomalies, abnormal sexual development, mental retardation and pathogenesis of malignancy [1]. Clinical features of patients with common autosomal or sex chromosome aneuploidy is shown in Table 1. © 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    [Show full text]
  • Your Baby and Down Syndrome
    • • I thought my pregnancy was What will the future hold for my normal. What happened? baby with Down syndrome? About 80% of children with Down People with Down syndrome have some level of Welcoming syndrome are born to mothers under intellectual disability, which can be anywhere your son or age 35. Mothers over 35 have a from mild to severe. Most are somewhere in daughter into higher chance of having a between. No one can look at any infant and the world will baby with Down syndrome. know how intelligent, successful or independent bring joy to you It’s not certain how or why he or she will be in the future. and your family. this happens. Without Your baby will be just specific medical tests, it like other babies in most is impossible to tell if an Today, people with Down unborn child might have ways. He or she will play, enjoy life and like syndrome are achieving more Down syndrome. to learn new things. Like any parent, you with advances in health care and may have some questions about your baby. increased opportunities in education. With support, many can: This brochure is a starting point for learning • move out of the family home about Down syndrome, resources and • take care of themselves support groups. • hold regular jobs • participate in leisure activities congratulations • live rich and full lives answers How might Down syndrome to questions you might have affect my baby’s health? Babies with Down syndrome might be affected What is Down syndrome? What if I want to have another baby? by any of the following health conditions: There are about 350,000 people in the United If you are planning to have more children, ask your • difficulty breastfeeding States with Down syndrome, the most common doctor about your chances for having another child • low muscle tone genetic disorder.
    [Show full text]