Editing Down syndrome (section)

==Signs and symptoms==
[[File:Autism somali Center 01.jpg|upright=1.2|thumb|A boy from Somalia with Down syndrome ]]
Those with Down syndrome nearly always have physical and intellectual disabilities.<ref>{{cite book | veditors = Faragher R, Clarke B | chapter = Introduction | title=Educating Learners with Down Syndrome: Research, theory, and practice with children and adolescents | publisher=Taylor & Francis | year=2013 | isbn=978-1-134-67335-3 | chapter-url=https://books.google.com/books?id=0Y20AQAAQBAJ&pg=PA5 | page=5 | url-status=live | archive-url=https://web.archive.org/web/20170123082416/https://books.google.com/books?id=0Y20AQAAQBAJ&lpg=PR11&pg=PA5 | archive-date=2017-01-23}}</ref> As adults, their mental abilities are typically similar to those of an 8- or 9-year-old.<ref name=Malt2013/> At the same time, their emotional and social awareness is very high.<ref>{{cite journal | vauthors = Hippolyte L, Iglesias K, Van der Linden M, Barisnikov K | title = Social reasoning skills in adults with Down syndrome: the role of language, executive functions and socio-emotional behaviour | journal = Journal of Intellectual Disability Research | volume = 54 | issue = 8 | pages = 714–726 | date = August 2010 | pmid = 20590998 | doi = 10.1111/j.1365-2788.2010.01299.x }}</ref> They can have [[immunodeficiency|poor immune function]]<ref name=Steph2010/> and generally reach [[developmental milestones]] at a later age.<ref name=Nelson2011/> They have an increased risk of a number of health concerns, such as [[congenital heart defect]], [[epilepsy]], [[leukemia]], and [[thyroid disease]]s.<ref name=Hick2012/>

{| class="wikitable"
|-
!Characteristics
!Percentage
!Characteristics
!Percentage
|-
|Mental impairment
| 99%<ref>{{cite book | vauthors = Johnston JM, Smyth MD, McKinstry RC | chapter = Basics of Neuroimaging in Pediatric Epilepsy | veditors = Pellock JM, Bourgeois BF, Dodson WE, Nordli Jr DR, Sankar R |title=Pediatric epilepsy diagnosis and therapy|year=2008|publisher=Demos Medical Pub.|location=New York|isbn=978-1-934559-86-4|page=Chapter 67| chapter-url=https://books.google.com/books?id=47fckyBY2XwC&pg=PA216-IA51|edition=3rd|url-status=live|archive-url=https://web.archive.org/web/20170123082424/https://books.google.com/books?id=47fckyBY2XwC&pg=PA216-IA51|archive-date=2017-01-23}}</ref>
|Abnormal teeth
| 60%<ref name=Eps2007>{{cite book| vauthors = Epstein CJ |title=The consequences of chromosome imbalance: principles, mechanisms, and models |year=2007 |publisher=Cambridge University Press |location=Cambridge |isbn=978-0-521-03809-6 |pages=255–256 |url=https://books.google.com/books?id=6SzKSM1t9MYC&pg=PA255 |url-status=live|archive-url=https://web.archive.org/web/20170123082736/https://books.google.com/books?id=6SzKSM1t9MYC&pg=PA255|archive-date=2017-01-23}}</ref>
|-
|Stunted growth
| 90%<ref>{{cite book | vauthors = Marion RW, Samanich JN | chapter = Genetics |title=Pediatrics for medical students|year=2012|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-7030-9|page=259| chapter-url = https://books.google.com/books?id=z0ohenkQrY0C&pg=PA259 | veditors = Bernstein D, Shelov SP |edition=3rd|url-status=live|archive-url=https://web.archive.org/web/20170123082701/https://books.google.com/books?id=z0ohenkQrY0C&pg=PA259|archive-date=2017-01-23}}</ref>
|[[Epicanthic fold|Slanted eyes]]
| 60%<ref name=Steph2010/>
|-
|[[Umbilical hernia]]
| 90%<ref>{{cite book| vauthors = Bertoti DB, Smith DE | chapter = Mental Retardation: Focus on Down Syndrome | veditors = Tecklin JS |title=Pediatric physical therapy|year=2008|publisher=Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-5399-9|page=380| chapter-url = https://books.google.com/books?id=YX8pztQHX0MC&pg=PA380|edition=4th|url-status=live|archive-url=https://web.archive.org/web/20170123082243/https://books.google.com/books?id=YX8pztQHX0MC&pg=PA380|archive-date=2017-01-23}}</ref>
|Shortened hands
| 60%<ref name=Eps2007/>
|-
| Increased skin on back of neck
| 80%<ref name=Hick2012/>
|Short neck
| 60%<ref name=Eps2007/>
|-
|[[Hypotonia|Low muscle tone]]
| 80%<ref name=Dom2007>{{cite book| veditors = Domino FJ |title=The 5-minute clinical consult 2007|year=2007|publisher=Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-6334-9|page=392|url=https://books.google.com/books?id=WSUMZ5ECEbMC&pg=PA392|edition=2007|url-status=live|archive-url=https://web.archive.org/web/20170123082614/https://books.google.com/books?id=WSUMZ5ECEbMC&pg=PA392|archive-date=2017-01-23}}</ref>
|[[Obstructive sleep apnea]]
| 60%<ref name=Hick2012/>
|-
|Narrow [[palate|roof of mouth]]
| 76%<ref name=Eps2007/>
|[[Clinodactyly|Bent fifth finger tip]]
| 57%<ref name=Steph2010/>
|-
|[[Brachycephaly|Flat head]]
| 75%<ref name=Steph2010/>
|[[Brushfield spots]] in the [[iris (anatomy)|iris]]
| 56%<ref name=Steph2010/>
|-
|Flexible ligaments
| 75%<ref name=Steph2010/>
|[[Single transverse palmar crease]]
| 53%<ref name=Steph2010/>
|-
|[[Macroglossia|Proportionally large tongue]]<ref name=Perk2009>{{cite journal | vauthors = Perkins JA | title = Overview of macroglossia and its treatment | journal = Current Opinion in Otolaryngology & Head and Neck Surgery | volume = 17 | issue = 6 | pages = 460–465 | date = December 2009 | pmid = 19713845 | doi = 10.1097/moo.0b013e3283317f89 | s2cid = 45941755 }}</ref>
| 75%<ref name=Dom2007/>
|Protruding tongue
| 47%<ref name=Eps2007/>
|-
|Abnormal [[pinna (anatomy)|outer ears]]
| 70%<ref name=Hick2012/>
|[[Congenital heart disease]]
| 40%<ref name=Eps2007/>
|-
|Flattened nose
| 68%<ref name=Steph2010/>
|[[Strabismus]]
| ≈35%<ref name=Wei2010/>
|-
|Separation of first and second toes
| 68%<ref name=Eps2007/>
|[[Undescended testicles]]
| 20%<ref>{{cite book| vauthors = Wilson GN, Cooley WC |title=Preventive management of children with congenital anomalies and syndromes.|year=2006|publisher=Cambridge University Press|location=Cambridge|isbn=978-0-521-61734-5|page=190|url=https://books.google.com/books?id=k0AHKmax9gwC&pg=PA190|edition=2nd | url-status=live|archive-url=https://web.archive.org/web/20170123082838/https://books.google.com/books?id=k0AHKmax9gwC&pg=PA190|archive-date=2017-01-23}}</ref>
|}

===Physical===
[[File:Feet of a boy with Down Syndrome.JPG|thumb|upright=1.4|Feet of a boy with Down syndrome, showing the deviated first toes]]
People with Down syndrome may have these physical characteristics: a [[microgenia|small chin]], [[epicanthic fold]]s, [[Hypotonia|low muscle tone]], a flat [[nasal bridge]], and a protruding tongue. A protruding tongue is caused by low tone and weak facial muscles, and often corrected with myofunctional exercises.<ref>{{Cite book | vauthors = Kumin L |title=Resource Guide to Oral Motor Skill Difficulties in Children with Down Syndrome |publisher=Loyola College of Maryland |location= | url = https://www.ndsccenter.org/wp-content/uploads/OralMotor.pdf }}</ref> Some characteristic airway features can lead to [[obstructive sleep apnea]] in around half of those with Down syndrome.<ref name=Hick2012/> Other common features include: excessive joint flexibility, extra space between [[Hallux|big toe]] and second toe, a [[Single transverse palmar crease|single crease of the palm]],  and short fingers.<ref name=Eps2007/><ref name=Dom2007/>

Instability of the [[atlantoaxial joint]] occurs in about 1–2%.<ref>{{cite journal | vauthors = Bull MJ, Trotter T, Santoro SL, Christensen C, Grout RW, Burke LW, Berry SA, Geleske TA, Holm I, Hopkin RJ, Introne WJ, Lyons MJ, Monteil DC, Scheuerle A, Stoler JM, Vergano SA, Chen E, Hamid R, Downs SM, Grout RW, Cunniff C, Parisi MA, Ralston SJ, Scott JA, Shapira SK, Spire P | display-authors = 6 | collaboration = Council on Genetics | title = Health Supervision for Children and Adolescents With Down Syndrome | journal = Pediatrics | volume = 149 | issue = 5 | date = May 2022 | doi = 10.1542/peds.2022-057010 | pmid = 35490285 | s2cid = 248252638 | url = https://publications.aap.org/pediatrics/article/149/5/e2022057010/186778/Health-Supervision-for-Children-and-Adolescents?autologincheck=redirected }}</ref> Atlantoaxial instability may cause [[myelopathy]] due to cervical spinal cord compression later in life, this often manifests as new onset weakness, [[ataxia|problems with coordination]], bowel or bladder incontinence, and gait dysfunction.<ref name="Bull 2020">{{cite journal | vauthors = Bull MJ | title = Down Syndrome | journal = The New England Journal of Medicine | volume = 382 | issue = 24 | pages = 2344–2352 | date = June 2020 | pmid = 32521135 | doi = 10.1056/NEJMra1706537 | s2cid = 219586275 }}</ref> Serial imaging cannot reliably predict future cervical cord compression, but changes can be seen on neurological exam. The condition is surgically corrected with spine surgery.<ref name="Bull 2020" />

Growth in height is slower, resulting in adults who tend to have [[short stature]]—the average height for men is {{convert|154|cm|ftin|abbr=off}}, and for women is {{convert|142|cm|ftin|abbr=off}}.<ref>{{cite book|title=Williams Textbook of Endocrinology Expert Consult|year=2011|publisher=Elsevier Health Sciences|location=London|isbn=978-1-4377-3600-7|url=https://books.google.com/books?id=nbg1QOAObicC&pg=PT4756|edition=12th|url-status=live|archive-url=https://web.archive.org/web/20170123082306/https://books.google.com/books?id=nbg1QOAObicC&pg=PT4756|archive-date=2017-01-23}}</ref> Individuals with Down syndrome are at increased risk for [[obesity]] as they age due to hypothyroidism, other medical issues and lifestyle.<ref name=Hick2012/><ref>{{cite journal | vauthors = Pierce M, Ramsey K, Pinter J | title = Trends in Obesity and Overweight in Oregon Children With Down Syndrome | journal = Global Pediatric Health | volume = 6 | pages = 2333794X19835640 | date = 2 April 2019 | pmid = 31044152 | pmc = 6446252 | doi = 10.1177/2333794X19835640 }}</ref> [[Growth chart]]s have been developed specifically for children with Down syndrome.<ref name=Hick2012/>

===Neurological===
[[File:A boy with Down syndrome using cordless drill to assemble a book case.jpg|upright=1.2|thumb|A boy with Down syndrome using a cordless drill to assemble a book case]]
This syndrome causes about a third of cases of intellectual disability.<ref name=Steph2010/> Many developmental milestones are delayed with the ability to crawl typically occurring around 8–22 months rather than 6–12 months, and the ability to walk independently typically occurring around 1–4 years rather than 9–18 months.<ref>{{Cite web |title=Early Development for Children with Down Syndrome |url=https://www.cambscommunityservices.nhs.uk/Bedfordshire/services/occupational-therapy/ot-leaflets/down-syndrome |access-date=28 March 2023 |website=INHS Cambridgeshire Community Services NHS Trust}}</ref> Walking is acquired in 50% of children after 24 months.<ref>{{cite journal | vauthors = Winders P, Wolter-Warmerdam K, Hickey F | title = A schedule of gross motor development for children with Down syndrome | journal = Journal of Intellectual Disability Research | volume = 63 | issue = 4 | pages = 346–356 | date = April 2019 | pmid = 30575169 | doi = 10.1111/jir.12580 | s2cid = 58592265 }}</ref>

Most individuals with Down syndrome have mild (IQ: 50–69) or moderate (IQ: 35–50) [[intellectual disability]] with some cases having severe (IQ: 20–35) difficulties.<ref name=Wei2010/><ref name=Reil2012>{{cite journal | vauthors = Reilly C | title = Behavioural phenotypes and special educational needs: is aetiology important in the classroom? | journal = Journal of Intellectual Disability Research | volume = 56 | issue = 10 | pages = 929–946 | date = October 2012 | pmid = 22471356 | doi = 10.1111/j.1365-2788.2012.01542.x | doi-access = free }}</ref> Those with mosaic Down syndrome typically have IQ scores 10–30 points higher than that.<ref>{{cite book|title=Children with disabilities|year=2005|publisher=Paul H. Brookes|location=Baltimore [u.a.]|isbn=978-1-55766-581-2|page=308|url=https://books.google.com/books?id=P65sAAAAMAAJ&q=IQ+%22mosaic+down+syndrome%22|edition=5th| veditors = Batshaw M |url-status=live|archive-url=https://web.archive.org/web/20170123082658/https://books.google.com/books?id=P65sAAAAMAAJ&q=IQ+%22mosaic+down+syndrome%22|archive-date=2017-01-23}}</ref> As they age, the gap tends to widen between people with Down syndrome and their same-age peers.<ref name=Reil2012/><ref>{{cite journal | vauthors = Patterson T, Rapsey CM, Glue P | title = Systematic review of cognitive development across childhood in Down syndrome: implications for treatment interventions | journal = Journal of Intellectual Disability Research | volume = 57 | issue = 4 | pages = 306–318 | date = April 2013 | pmid = 23506141 | doi = 10.1111/j.1365-2788.2012.01536.x }}</ref>

Commonly, individuals with Down syndrome have better language understanding than ability to speak.<ref name=Hick2012/><ref name=Reil2012/> [[Babbling]] typically emerges around 15 months on average.<ref>{{cite journal | vauthors = Windsperger K, Hoehl S | title = Development of Down Syndrome Research Over the Last Decades-What Healthcare and Education Professionals Need to Know | journal = Frontiers in Psychiatry | volume = 12 | pages = 749046 | date = 2021 | pmid = 34970162 | pmc = 8712441 | doi = 10.3389/fpsyt.2021.749046 | doi-access = free }}</ref> 10–45% of those with Down syndrome have either a [[stutter]] or [[cluttering|rapid and irregular speech]], making it difficult to understand them.<ref>{{cite journal | vauthors = Kent RD, Vorperian HK | title = Speech impairment in Down syndrome: a review | journal = Journal of Speech, Language, and Hearing Research | volume = 56 | issue = 1 | pages = 178–210 | date = February 2013 | pmid = 23275397 | pmc = 3584188 | doi = 10.1044/1092-4388(2012/12-0148) }}</ref> After reaching 30&nbsp;years of age, some may lose their ability to speak.<ref name=Malt2013/>

They typically do fairly well with social skills.<ref name=Hick2012/> Behavior problems are not generally as great an issue as in other syndromes associated with intellectual disability.<ref name=Reil2012/> In children with Down syndrome, [[mental illness]] occurs in nearly 30% with [[autism spectrum|autism]] occurring in 5–10%.<ref name=Nelson2011/> People with Down syndrome experience a wide range of emotions.<ref>{{cite book| vauthors = McGuire D, Chicoine B |title=Mental Wellness in Adults with Down Syndrome|year=2006|publisher=Woodbine House, Inc.|location=Bethesday, MD|isbn=978-1-890627-65-2|page=49}}</ref> While people with Down syndrome are generally happy,<ref>{{cite book| vauthors = Margulies P |title=Down syndrome|year=2007|publisher=Rosen Pub. Group|location=New York|isbn=978-1-4042-0695-3|page=[https://archive.org/details/downsyndrome0000marg/page/5 5]|url=https://archive.org/details/downsyndrome0000marg|url-access=registration|edition=1st}}</ref> symptoms of [[Depression (mood)|depression]] and [[anxiety (mood)|anxiety]] may develop in early adulthood.<ref name=Malt2013/>

Children and adults with Down syndrome are at increased risk of [[epileptic seizures]], which occur in 5–10% of children and up to 50% of adults.<ref name=Malt2013/> This includes an increased risk of a specific type of seizure called [[infantile spasms]].<ref name=Hick2012/> Many (15%) who live 40 years or longer develop [[Alzheimer's disease]].<ref>{{cite book|title=The 5-minute pediatric consult|year=2012|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-1-4511-1656-4|page=289|url=https://books.google.com/books?id=v7pbSFfMHCoC&pg=PA289|edition=6th | veditors = Schwartz MW |url-status=live|archive-url= https://web.archive.org/web/20170123083059/https://books.google.com/books?id=v7pbSFfMHCoC&pg=PA289|archive-date=2017-01-23}}</ref> In those who reach 60&nbsp;years of age, 50–70% have the disease.<ref name="Malt2013"/>

[[Down syndrome regression disorder]] is a sudden [[Regression (medicine)|regression]] with [[neuropsychiatric]] symptoms such as [[catatonia]], possibly caused by an autoimmune disease.<ref>{{Cite journal |last1=Santoro |first1=Jonathan D. |last2=Filipink |first2=Robyn A. |last3=Baumer |first3=Nicole T. |last4=Bulova |first4=Peter D. |last5=Handen |first5=Benjamin L. |date=2023-03-01 |title=Down syndrome regression disorder: updates and therapeutic advances |url=https://pubmed.ncbi.nlm.nih.gov/36705008 |journal=Current Opinion in Psychiatry |volume=36 |issue=2 |pages=96–103 |doi=10.1097/YCO.0000000000000845 |issn=1473-6578 |pmid=36705008}}</ref>  It primarily appears in teenagers and younger adults.<ref>{{Cite book |last1=Skoto |first1=Brian G. |chapter-url=https://books.google.com/books?id=KYUCEQAAQBAJ&dq=%22Down+syndrome+regression+disorder%22&pg=PT1514 |title=The 5-Minute Clinical Consult 2025 |last2=Roberts |first2=Michele |date=2024-02-28 |publisher=Lippincott Williams & Wilkins |isbn=978-1-9752-3473-7 |editor-last=Domino |editor-first=Frank J. |language=en |chapter=Down Syndrome}}</ref>

===Senses===
[[File:Brushfield eye crop.jpg|thumb|upright=1.5|[[Brushfield spots]], visible in the irises of a baby with Down syndrome]]
Hearing and vision disorders occur in more than half of people with Down syndrome.<ref name=Hick2012/> 
<!-- Vision -->

==== Ocular findings ====
[[Brushfield spots]] (small white or grayish/brown spots on the periphery of the [[Iris (anatomy)|iris]]), upward slanting [[palpebral fissure]]s (the opening between the upper and lower lids) and [[Epicanthic folds|epicanthal folds]] (folds of skin between the upper eyelid and the nose) are clinical signs at birth suggesting the diagnosis of Down syndrome<ref name="Wei20102">{{cite journal |vauthors=Weijerman ME, de Winter JP |date=December 2010 |title=Clinical practice. The care of children with Down syndrome |journal=European Journal of Pediatrics |volume=169 |issue=12 |pages=1445–1452 |doi=10.1007/s00431-010-1253-0 |pmc=2962780 |pmid=20632187}}</ref><ref name=":02">{{Cite web |title=Trisomy 21/Down Syndrome - EyeWiki |url=https://eyewiki.org/Trisomy_21/Down_Syndrome#Diagnosis |access-date=2024-05-07 |website=eyewiki.org |language=en}}</ref> especially in the [[Western world|Western World]].<ref name=":02"/>  None of these requires treatment.{{Citation needed|date=May 2024}}

Visually significant congenital [[cataract]]s (clouding of the [[Lens (vertebrate anatomy)|lens]] of the eye) occur more frequently with Down syndrome.<ref name=":02"/> [[Infant|Neonates]] with Down syndrome should be screened for cataract because early recognition and referral reduce the risk of vision loss from [[amblyopia]].<ref name=":13">{{Cite journal |last1=Bull |first1=Marilyn J. |last2=Trotter |first2=Tracy |last3=Santoro |first3=Stephanie L. |last4=Christensen |first4=Celanie |last5=Grout |first5=Randall W. |last6=THE COUNCIL ON GENETICS |date=2022-05-01 |title=Health Supervision for Children and Adolescents With Down Syndrome |url=https://publications.aap.org/pediatrics/article/149/5/e2022057010/186778/Health-Supervision-for-Children-and-Adolescents |journal=Pediatrics |language=en |volume=149 |issue=5 |doi=10.1542/peds.2022-057010 |pmid=35490285 |issn=0031-4005}}</ref>  Dot-like opacities in the cortex of the [[Lens (anatomy)|lens]] (cerulean cataract) are present in up to 50% of people with Down syndrome, but may be followed without treatment if they are not visually significant.<ref name=":02"/>

[[Strabismus]], [[nystagmus]] and [[nasolacrimal duct obstruction]] occur more frequently in children with Down syndrome.<ref name=":02"/>  Screening for these diagnoses should begin within six months of birth.<ref name=":02"/><ref name=":13" />  Strabismus is more often acquired than [[congenital]].<ref name=":02"/>  Early diagnosis and treatment of strabismus reduces the risk of vision loss from amblyopia.<ref name=":63">{{Cite web |title=Strabismus and Amblyopia {{!}} Boston Children's Hospital |url=https://www.childrenshospital.org/conditions/strabismus-and-amblyopia#:~:text=Early%20diagnosis%20is%20essential%20in,the%20eyes%20are%20not%20aligned. |access-date=2024-05-08 |website=www.childrenshospital.org}}</ref>  In Down syndrome, the presence of epicanthal folds may give the false impression of [[strabismus]], referred to as [[pseudostrabismus]]. Nasolacrimal duct obstruction, which causes tearing ([[Epiphora (medicine)|epiphora]]), is more frequently bilateral and multifactorial than in children without Down syndrome.<ref name=":02"/>

[[Refractive error]] is more common with Down syndrome, though the rate may not differ until after twelve months of age compared to children without Down syndrome.<ref name=":02"/> Early screening is recommended to identify and treat significant refractive error with glasses or contact lenses. Poor [[Accommodation reflex|accommodation]] (ability to focus on close objects) is associated with Down syndrome, which may mean bifocals are indicated.<ref name=":02"/>

In [[keratoconus]], the [[cornea]] progressively thins and bulges into a cone shape,<ref name=":23">{{Cite web |title=Keratoconus - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/keratoconus/symptoms-causes/syc-20351352 |access-date=2024-05-08 |website=Mayo Clinic |language=en}}</ref> causing visual blurring or distortion. Keratoconus first presents in the teen years and progresses into the thirties.<ref name=":23" /><ref name=":33">{{Cite web |date=2021-08-08 |title=Keratoconus |url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/keratoconus |access-date=2024-05-08 |website=www.hopkinsmedicine.org |language=en}}</ref> Down syndrome is a strong risk factor for developing keratoconus, and onset may be occur at a younger age than in those without Down syndrome.<ref name=":02"/>  Eye rubbing is also a risk factor for developing keratoconus.<ref name=":33" />  It is speculated that chronic eye irritation from [[blepharitis]] may increase eye rubbing in Down syndrome,<ref name=":02"/> contributing to the increased prevalence of keratoconus.

An association between [[glaucoma]] and Down syndrome is often cited.<ref name="Wei20102"/>  Glaucoma in children with Down syndrome is uncommon, with a prevalence of less than 1%.<ref name="Wei20102"/><ref name=":02"/>  It is currently unclear if the prevalence of glaucoma in those with Down syndrome differs from that in the absence of Down syndrome.<ref name=":02"/>

Estimates of [[prevalence]] of ocular findings in Down Syndrome vary widely depending on the study.<ref name=":02"/>  Some prevalence estimates follow. Vision problems have been observed in 38–80% of cases.<ref name="Wei20102"/> [[Brushfield spots]] are present in 38–85% of individuals.<ref name="Wei20102" />  Between 20 and 50% have [[strabismus]].<ref name="Wei20102" /> [[Cataract]]s occur in 15%,<ref name="Nelson20112">{{cite book |title=Nelson textbook of pediatrics |vauthors=Kliegma RM |publisher=Saunders |year=2011 |isbn=978-1-4377-0755-7 |edition=19th |location=Philadelphia |pages=Chapter 76.2 |chapter=Down Syndrome and Other Abnormalities of Chromosome Number}}</ref> and may be present at birth.<ref name="Wei20102" /> [[Keratoconus]] may occur in as many as 21–30%.<ref name=":02" />

==== <!-- Hearing -->Hearing loss ====
Hearing problems are found in 50–90% of children with Down syndrome.<ref name=Rod2012/> This is often the result of [[otitis media with effusion]] which occurs in 50–70%<ref name=Nelson2011/> and chronic [[otitis media|ear infections]] which occur in 40–60%.<ref>{{cite book| vauthors = Evans-Martin FF |title=Down syndrome|year=2009|publisher=Chelsea House|location=New York|isbn=978-1-4381-1950-2|page=[https://archive.org/details/downsyndrome0000evan/page/71 71]|url=https://archive.org/details/downsyndrome0000evan|url-access=registration}}</ref> Ear infections often begin in the first year of life and are partly due to poor [[eustachian tube]] function.<ref name=Tint2010/><ref name=Sam2011>{{cite book|title=Handbook of neurodevelopmental and genetic disorders in children|year=2011|publisher=Guilford Press|location=New York|isbn=978-1-60623-990-2|page=365|url=https://books.google.com/books?id=Mm81tZFxf9UC&pg=PA365|edition=2nd| veditors = Goldstein S |url-status=live|archive-url=https://web.archive.org/web/20170123082556/https://books.google.com/books?id=Mm81tZFxf9UC&pg=PA365|archive-date=2017-01-23}}</ref> Excessive [[Earwax|ear wax]] can also cause hearing loss due to obstruction of the outer [[ear canal]].<ref name=Malt2013/> Even a mild degree of hearing loss can have negative consequences for speech, language understanding, and academics.<ref name=Wei2010/><ref name=Sam2011/> It is important to rule out hearing loss as a factor in social and cognitive deterioration.<ref>{{cite book| vauthors = Prasher VP |title=Neuropsychological assessments of dementia in Down syndrome and intellectual disabilities |year=2009 |publisher=Springer |location=London |isbn=978-1-84800-249-4 |page=56 |url= https://books.google.com/books?id=RBQKsxodntgC&pg=PA56 |url-status=live |archive-url= https://web.archive.org/web/20170123082925/https://books.google.com/books?id=RBQKsxodntgC&pg=PA56|archive-date=2017-01-23}}</ref> Age-related hearing loss of the [[Sensorineural hearing loss|sensorineural type]] occurs at a much earlier age and affects 10–70% of people with Down syndrome.<ref name=Malt2013/>

===Heart===
The rate of [[congenital heart disease]] in newborns with Down syndrome is around 40%.<ref name=Eps2007/> Of those with heart disease, about 80% have an [[atrial septal defect]] or [[ventricular septal defect]] with the former being more common.<ref name=Malt2013/> Congenital heart disease can also put individuals at a higher risk of [[pulmonary hypertension]], where arteries in the lungs narrow and cause inadequate blood oxygenation.<ref name=":3">{{cite journal | vauthors = Bush D, Galambos C, Dunbar Ivy D | title = Pulmonary hypertension in children with Down syndrome | journal = Pediatric Pulmonology | volume = 56 | issue = 3 | pages = 621–629 | date = March 2021 | pmid = 32049444 | doi = 10.1002/ppul.24687 | s2cid = 211087826 }}</ref> Some of the genetic contributions to pulmonary hypertension in individuals with Down Syndrome are abnormal lung development, [[endothelial dysfunction]], and proinflammatory genes.<ref name=":3" /> [[Mitral valve]] problems become common as people age, even in those without heart problems at birth.<ref name=Malt2013/> Other problems that may occur include [[tetralogy of Fallot]] and [[patent ductus arteriosus]].<ref name=Tint2010>{{cite book | vauthors = Tintinalli JE |title=Emergency Medicine: A Comprehensive Study Guide (Emergency Medicine (Tintinalli)) |publisher=McGraw-Hill Companies |location=New York |year=2010 |pages=Chapter 138|chapter=The Child with Special Health Care Needs|isbn=978-0-07-148480-0}}</ref> People with Down syndrome have a lower risk of [[atherosclerosis|hardening of the arteries]].<ref name=Malt2013/>

===Cancer===
Although the overall risk of [[cancer]] in Down syndrome is not changed,<ref name=UrbanoP129>{{cite book| vauthors = Urbano R |title=Health Issues Among Persons With Down Syndrome|url=https://books.google.com/books?id=QbHL8qrgfCoC&pg=PA129|date=9 September 2010|publisher=Academic Press|isbn=978-0-12-374477-7|page=129|url-status=live|archive-url=https://web.archive.org/web/20150512114141/http://books.google.com/books?id=QbHL8qrgfCoC&pg=PA129|archive-date=12 May 2015}}</ref> the risk of [[testicular cancer]] and certain blood cancers, including [[acute lymphoblastic leukemia]] (ALL) and [[acute megakaryoblastic leukemia]] (AMKL) is increased while the risk of other non-blood cancers is decreased.<ref name=Malt2013/> People with Down syndrome are believed to have an increased risk of developing cancers derived from [[germ cell]]s whether these cancers are blood- or non-blood-related.<ref name=Nix2018/> In 2008, the World Health Organization (WHO) introduced a distinct classification for myeloid proliferation in individuals with Down syndrome.<ref>{{cite journal | vauthors = Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-Lindberg E, Tefferi A, Bloomfield CD | display-authors = 6 | title = The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes | journal = Blood | volume = 114 | issue = 5 | pages = 937–951 | date = July 2009 | pmid = 19357394 | doi = 10.1182/blood-2009-03-209262 }}</ref>

==== Blood cancers ====
[[Leukemia]] is 10 to 15 times more common in children with Down syndrome.<ref name=Hick2012/> In particular, [[acute lymphoblastic leukemia]] is 20 times more common and the megakaryoblastic form of [[acute myeloid leukemia]] ([[acute megakaryoblastic leukemia]]), is 500 times more common.<ref name="pmid22867885"/> Acute megakaryoblastic leukemia (AMKL) is a leukemia of [[megakaryoblast]]s, the precursors cells to [[megakaryocyte]]s which form blood [[platelet]]s.<ref name="pmid22867885">{{cite journal | vauthors = Seewald L, Taub JW, Maloney KW, McCabe ER | title = Acute leukemias in children with Down syndrome | journal = Molecular Genetics and Metabolism | volume = 107 | issue = 1–2 | pages = 25–30 | date = September 2012 | pmid = 22867885 | doi = 10.1016/j.ymgme.2012.07.011 }}</ref> Acute lymphoblastic leukemia in Down syndrome accounts for 1–3% of all childhood cases of ALL. It occurs most often in those older than nine years or having a [[white blood cell count]] greater than 50,000 per [[microliter]] and is rare in those younger than one year old. ALL in Down syndrome tends to have poorer outcomes than other cases of ALL in people without Down syndrome.<ref name="pmid22867885"/><ref name="pmid27285583">{{cite journal | vauthors = Lee P, Bhansali R, Izraeli S, Hijiya N, Crispino JD | title = The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome | journal = Leukemia | volume = 30 | issue = 9 | pages = 1816–1823 | date = September 2016 | pmid = 27285583 | pmc = 5434972 | doi = 10.1038/leu.2016.164 }}</ref>  In short, the likelihood of developing acute myeloid leukemia (AML) and [[acute lymphoblastic leukemia]] (ALL) is higher in children with Down syndrome compared to those without Down syndrome.<ref>{{cite journal | vauthors = Li J, Kalev-Zylinska ML | title = Advances in molecular characterization of myeloid proliferations associated with Down syndrome | journal = Frontiers in Genetics | volume = 13 | pages = 891214 | date = 2022 | pmid = 36035173 | pmc = 9399805 | doi = 10.3389/fgene.2022.891214 | doi-access = free }}</ref>

[[Myeloid leukemia]] typically precedes Down syndrome and is accompanied by a condition known as [[Transient myeloproliferative disease|transient abnormal myelopoiesis]] (TAM), which generally disrupts the differentiation of megakaryocytes and erythrocytes.<ref name="The paradox of Myeloid Leukemia ass">{{cite journal | vauthors = Gupte A, Al-Antary ET, Edwards H, Ravindranath Y, Ge Y, Taub JW | title = The paradox of Myeloid Leukemia associated with Down syndrome | journal = Biochemical Pharmacology | volume = 201 | pages = 115046 | date = July 2022 | pmid = 35483417 | doi = 10.1016/j.bcp.2022.115046 | s2cid = 248431139 }}</ref> In Down syndrome, AMKL is typically preceded by [[transient myeloproliferative disease]] (TMD), a disorder of [[Haematopoiesis|blood cell production]] in which non-cancerous megakaryoblasts with a mutation in the ''[[GATA1]]'' gene rapidly divide during the later period of pregnancy.<ref name="pmid22867885"/><ref name="pmid25956670">{{cite journal | vauthors = Tamblyn JA, Norton A, Spurgeon L, Donovan V, Bedford Russell A, Bonnici J, Perkins K, Vyas P, Roberts I, Kilby MD | display-authors = 6 | title = Prenatal therapy in transient abnormal myelopoiesis: a systematic review | journal = Archives of Disease in Childhood. Fetal and Neonatal Edition | volume = 101 | issue = 1 | pages = F67–F71 | date = January 2016 | pmid = 25956670 | doi = 10.1136/archdischild-2014-308004 | s2cid = 5958598 | url = https://ora.ox.ac.uk/objects/uuid:73db9b1c-e082-43bc-91a5-db03b26d18d3 }}</ref> GATA1 mutations combined with trisomy 21 contribute to a predisposition to TAM.<ref name="pmid27510823"/> In trisomy 21, the process of leukemogenesis starts in early fetal life, with genetic factors, including GATA1 mutations, contributing to the development of TAM on the preleukemic pathway.<ref name="The paradox of Myeloid Leukemia ass"/> The condition affects 3–10% of babies with Down.<ref name="pmid22867885"/> While it often spontaneously resolves within three months of birth, it can cause serious blood, liver, or other complications.<ref name=Gam2012>{{cite journal | vauthors = Gamis AS, Smith FO | title = Transient myeloproliferative disorder in children with Down syndrome: clarity to this enigmatic disorder | journal = British Journal of Haematology | volume = 159 | issue = 3 | pages = 277–287 | date = November 2012 | pmid = 22966823 | doi = 10.1111/bjh.12041 | s2cid = 37593917 | doi-access = free }}</ref> In about 10% of cases, TMD progresses to AMKL during the three months to five years following its resolution.<ref name="pmid22867885"/><ref name=Gam2012/><ref name="pmid27510823">{{cite journal | vauthors = Bhatnagar N, Nizery L, Tunstall O, Vyas P, Roberts I | title = Transient Abnormal Myelopoiesis and AML in Down Syndrome: an Update | journal = Current Hematologic Malignancy Reports | volume = 11 | issue = 5 | pages = 333–341 | date = October 2016 | pmid = 27510823 | pmc = 5031718 | doi = 10.1007/s11899-016-0338-x }}</ref>

==== Non-blood cancers ====
People with Down syndrome have a lower risk of all major solid cancers, including those of lung, breast, and cervix, with the lowest relative rates occurring in those aged 50 years or older.<ref name=Nix2018/> This low risk is thought to be due to an increase in the expression of [[tumor suppressor gene]]s present on chromosome 21.<ref>{{cite book|title=Cancer genome and tumor microenvironment |year=2010 |publisher=Springer|location=New York|isbn=978-1-4419-0711-0|page=203|url=https://books.google.com/books?id=x3Lb9Mxl4qcC&pg=PA203|edition=Online-Ausg.| veditors = Thomas-Tikhonenko A |url-status=live|archive-url=https://web.archive.org/web/20150704142502/https://books.google.com/books?id=x3Lb9Mxl4qcC&pg=PA203|archive-date=2015-07-04}}</ref><ref name=Nix2018>{{cite journal | vauthors = Nixon DW | title = Down Syndrome, Obesity, Alzheimer's Disease, and Cancer: A Brief Review and Hypothesis | journal = Brain Sciences | volume = 8 | issue = 4 | page = 53 | date = March 2018 | pmid = 29587359 | pmc = 5924389 | doi = 10.3390/brainsci8040053 | doi-access = free }}</ref> One exception is testicular [[Germ cell tumor|germ cell cancer]] which occurs at a higher rate in Down syndrome.<ref name=Nix2018/>

===Endocrine===
Problems of the [[thyroid gland]] occur in 20–50% of individuals with Down syndrome.<ref name=Malt2013/><ref name=Hick2012/> [[Hypothyroidism|Low thyroid]] is the most common form, occurring in almost half of all individuals.<ref name=Malt2013/> Thyroid problems can be due to a poorly or nonfunctioning thyroid at birth (known as [[congenital hypothyroidism]]) which occurs in 1%<ref name=Nelson2011/> or can develop later due to an attack on the thyroid by the [[immune system]] resulting in [[Graves' disease]] or [[autoimmune hypothyroidism]].<ref>{{cite journal | vauthors = Graber E, Chacko E, Regelmann MO, Costin G, Rapaport R | title = Down syndrome and thyroid function | journal = Endocrinology and Metabolism Clinics of North America | volume = 41 | issue = 4 | pages = 735–745 | date = December 2012 | pmid = 23099267 | doi = 10.1016/j.ecl.2012.08.008 }}</ref> [[Type 1 diabetes mellitus]] is also more common.<ref name=Malt2013/>

===Gastrointestinal===
[[Constipation]] occurs in nearly half of people with Down syndrome and may result in changes in behavior.<ref name=Hick2012/> One potential cause is [[Hirschsprung's disease]], occurring in 2–15%, which is due to a lack of [[Neuron|nerve cells]] controlling the [[colon (anatomy)|colon]].<ref>{{cite journal | vauthors = Moore SW | title = Down syndrome and the enteric nervous system | journal = Pediatric Surgery International | volume = 24 | issue = 8 | pages = 873–883 | date = August 2008 | pmid = 18633623 | doi = 10.1007/s00383-008-2188-7 | s2cid = 11890549 }}</ref> Other congenital problems can include [[duodenal atresia]], [[imperforate anus]] and [[gastroesophageal reflux disease]].<ref name=Tint2010/> [[Celiac disease]] affects about 7–20%.<ref name="Malt2013" /><ref name="Hick2012" />

===Teeth===
People with Down syndrome tend to be more susceptible to [[gingivitis]] as well as early, severe [[Periodontal pathology|periodontal]] disease, [[Acute necrotizing ulcerative gingivitis|necrotising ulcerative gingivitis]], and early [[tooth loss]], especially in the lower front teeth.<ref name="Churchill">{{cite book| vauthors = Cawson RA, Odell EW |title=Cawson's essentials of oral pathology and oral medicine|date=2012|publisher=Churchill Livingstone|location=Edinburgh|isbn=978-0443-10125-0|pages=419–421|edition=8th}}</ref><ref name="Carranza">{{cite book | veditors = Newman MG, Takei HH, Klokkevold PR, Carranza FA |title=Carranza's clinical periodontology|date=2006|publisher=W.B. Saunders Co.|location=Philadelphia|isbn=978-1-4160-2400-2|pages=299, 397, 409, 623|edition=10th}}</ref> While [[Dental plaque|plaque]] and poor [[oral hygiene]] are contributing factors, the severity of these periodontal diseases cannot be explained solely by external factors.<ref name="Carranza"/> Research suggests that the severity is likely a result of a weakened immune system.<ref name="Carranza"/><ref name="Mosby">{{cite book | vauthors = Avery DR, Dean JA, McDonald RE |title=Dentistry for the child and adolescent |date=2004 |publisher=Mosby |isbn=978-0-323-02450-1 |edition=8th |location=St. Louis, Mo |pages=164–168, 190–194, 474}}</ref> The weakened immune system also contributes to increased incidence of [[Candidiasis|yeast infections]] in the mouth (from ''[[Candida albicans]]'').<ref name="Mosby"/>

People with Down syndrome also tend to have a more [[alkaline]] [[saliva]] resulting in a greater resistance to [[tooth decay]], despite decreased quantities of saliva,<ref name="ReferenceA">{{cite book| vauthors = Sapp JP, Eversole LR, Wysocki GP |title=Contemporary oral and maxillofacial pathology|date=2002|publisher=Mosby|location=St. Louis|isbn=978-0-323-01723-7|pages=39–40|edition=2nd}}</ref> less effective oral hygiene habits, and higher plaque indexes.<ref name="Churchill"/><ref name="Mosby"/><ref name="ReferenceA"/><ref name="Saunders">{{cite book| vauthors = Regezi JA, Sciubba JJ, Jordan RC |title=Oral Pathology: Clinical Pathologic Correlations|date=2008|publisher=Saunders Elsevier|location=St Louis, Missouri|isbn=978-1-4557-0262-6 |pages=353–354|edition=5th}}</ref>

Higher rates of tooth wear and [[bruxism]] are also common.<ref name="Mosby"/> Other common oral manifestations of Down syndrome include enlarged hypotonic tongue, crusted and hypotonic lips, [[mouth breathing]], narrow [[palate]] with crowded teeth, class III [[malocclusion]] with an underdeveloped maxilla and posterior [[crossbite]], delayed exfoliation of [[baby teeth]] and delayed eruption of adult teeth, shorter roots on teeth, and often missing and malformed (usually smaller) teeth.<ref name="Churchill" /><ref name="Mosby"/><ref name="ReferenceA"/><ref name="Saunders"/> Less common manifestations include [[cleft lip and palate]] and [[enamel hypocalcification]] (20% prevalence).<ref name="Saunders"/>

[[Taurodontism]], an elongation of the pulp chamber, has a high prevalence in people with DS.<ref>{{cite journal | vauthors = Bell J, Civil CR, Townsend GC, Brown RH | title = The prevalence of taurodontism in Down's syndrome | journal = Journal of Mental Deficiency Research | volume = 33 | issue = 6 | pages = 467–476 | date = December 1989 | pmid = 2533267 | doi = 10.1111/j.1365-2788.1989.tb01502.x }}</ref><ref>{{cite journal | vauthors = Rajić Z, Mestrović SR | title = Taurodontism in Down's syndrome | journal = Collegium Antropologicum | volume = 22 | issue = Suppl | pages = 63–67 | date = December 1998 | pmid = 9951142 | url = https://pubmed.ncbi.nlm.nih.gov/9951142/ }}</ref>

===Fertility===
Males with Down syndrome usually do not father children, while females have lower rates of [[fertility]] relative to those who are unaffected.<ref name=Prad2006/> Fertility is estimated to be present in 30–50% of females.<ref name=Nel2010/> [[Menopause]] usually occurs at an earlier age.<ref name=Malt2013/> The poor fertility in males is thought to be due to problems with [[spermatogenesis|sperm development]]; however, it may also be related to not being sexually active.<ref name=Prad2006>{{cite journal | vauthors = Pradhan M, Dalal A, Khan F, Agrawal S | title = Fertility in men with Down syndrome: a case report | journal = Fertility and Sterility | volume = 86 | issue = 6 | pages = 1765.e1–1765.e3 | date = December 2006 | pmid = 17094988 | doi = 10.1016/j.fertnstert.2006.03.071 | s2cid = 32384231 | doi-access = free }}</ref> Without [[preimplantation genetic diagnosis|assisted reproductive technologies]], around half of the children of someone with Down syndrome will also have the syndrome.<ref name=Prad2006/><ref name=Rubin2013/>