eMedicine Specialties > Ophthalmology > Genetic Disorders

Down Syndrome

Natalio J Izquierdo, MD, Associate Professor, Department of Ophthalmology, Medical Sciences Campus, University of Puerto Rico
William Townsend, MD, Professor and Director, Department of Pediatric Surgery, Section of Ophthalmology, University Pediatric Hospital, Puerto Rico Medical Center

Updated: Feb 14, 2008

Introduction

Background

Down syndrome is the trisomy of chromosome 21. This is the most common trisomy among live births. The syndrome was named after Langdon Down, who first coined the term mongolism because of the mongoloid facial appearance of patients with the syndrome. Nowadays, the term mongolism is obsolete.

Frequency

United States

In Caucasian and African American populations, the incidence rate is 1 per 600-700 live births.

International

In the Japanese population, the incidence rate is 1 per 700 live births.

Mortality/Morbidity

• Patients with Down syndrome have a shortened life expectancy. About one third of patients die within the first year, and one half of patients die as they reach 4 years. The remainder of patients with Down syndrome has a reduced life expectancy as compared to the general population.
• Congenital heart disease is the major cause of morbidity and early mortality in patients with the Down syndrome.
• Recurrent respiratory infections, epilepsy, intestinal obstruction, and leukemia may also affect patients with the syndrome.

Sex

A slight male preponderance is observed among patients with trisomy 21.

Age

Occurrence is strongly dependent on maternal age. The risk for recurrence of Down syndrome in a patient's siblings is also inherent to maternal age.

• For young mothers, the risk of a free trisomy is 1-2%.
• For mothers aged 20 years or younger, the occurrence is 1 per 2500 births.
• The risk increases considerably for mothers aged 35 years or older.
• For mothers aged 45 years or older, the occurrence is 1 per 55 live births.

Clinical

History

• Obtain history, usually from a third party.  
  • Determine the patient's age, and obtain a chief complaint.
  • In history of present illness, include parental age, previous eyeglass prescriptions, occlusion therapy, onset of strabismus and/or nystagmus, previous external infections and treatment modalities, tearing, and photophobia. Inquire about previous strabismus surgery and/or cataract surgery.
  • Review pulmonary, gastrointestinal, and neurological systems.
  • Review cardiovascular systems, and obtain history of any previous cardiovascular surgery, including complications associated to general anesthesia.

Physical

Eight or more of the characteristic clinical findings lead to a definite diagnosis. Chromosomal analysis is recommended and of utmost importance in doubtful cases. 

Patients with Down syndrome have characteristic craniofacial findings, such as flat occiput, a flattened facial appearance, anteriorly and posteriorly flattened head, dysplastic ears, small nose, depressed nasal bridge, protruding tongue, high-arched palate, dental abnormalities, and a short and broad neck.

General physical features in patients with Down syndrome include shortened extremities, short limbs, short and broad hands, short fifth middle phalanx, simian palmar creases (in approximately 60% of patients), joint hyperextensibility or hyperflexibility, neuromuscular hypotonia, dry skin, premature aging, a wide range of intelligence quotients, and congenital heart defects.

Ocular findings in patients with trisomy 21 include lid anomalies and infections, amblyopia, high refractive errors, strabismus, nystagmus, corneal ectasias, Brushfield spots, presenile cataracts, glaucoma, and retinovascular anomalies.

• Lid anomalies include prominent epicanthal folds, upward slanting of the palpebral fissures, and congenital ectropion (rare).
• Patients frequently have lid infections, including blepharitis, blepharoconjunctivitis, chalazion, and hordeola. Because of recurrent external infections, inspect lids for collarettes, foamy secretions, Meibomian plugging, marginal erythema, and scurf.
• Patients may have nasolacrimal duct obstruction.
• Patients with Down syndrome may develop amblyopia due to strabismus, refractive errors, or media opacities, such as cataracts.
• Visual acuity is evaluated according to the patient's intelligence and responsiveness.
  • In the nonverbal patient, vision is evaluated in terms of quality (good, fair, or poor), location (central versus eccentric), and duration (maintained versus sporadic).
  • In a verbal patient, visual acuity may be assessed using optotypes (eg, Allen or Tellen cards, tumbling E or Snellen charts).
• Up to 20% of patients with Down syndrome have strabismus. Goals of a strabismus examination are as follows:  
  • Evaluate the type of strabismus.
  • Measure the deviation.
  • Evaluate patients for the presence of nystagmus.
• Strabismus examination should include the following:
  • Inspection
  • Ductions and versions
  • Deviation measurement
  • Evaluation of face turns
  • Restriction and paresis evaluation
• Observe the patient's visual behavior, eye movements, fixation, alignment, and head posturing.
  • Methods for measuring ocular deviation include light reflex tests and cover tests. Light reflex tests are easier but not as precise as cover tests.
  • Presence of a head tilt or face turn usually indicates the presence of nystagmus with a null point or an incomitant strabismus with compensatory head positioning.
• Evaluate corneas carefully for keratoconus or keratoglobus.
  • Scissoring of the retinoscopic reflex is an early finding in patients with keratoconus.
  • Placido disks, keratometers, or topographies can be used to evaluate cooperative patients with Down syndrome who have keratoconus.
  • Rizzuti and Munson signs appear later.
• Brushfield spots occur in up to 90% of patients with trisomy 21.
  • Brushfield spots are focal areas of iris stromal hyperplasia, surrounded by relative hypoplasia.
  • The spots are more common in patients with lightly pigmented irides.
• Cataracts may be congenital or may occur later in life. Lens opacities may be sutural, zonular, or complete.
• Glaucoma usually appears during infancy. Therefore, patients must be examined for corneal edema, megalocornea, increased intraocular pressure, and optic nerve cupping.
• Previous studies describe an increased number of retinal vessels crossing the disk margin. Retinal detachments have been reported in patients with Down syndrome.
• A cycloplegic refraction is of utmost importance, since patients with Down syndrome may have high refractory errors.

Causes

• Various chromosomal abnormalities may lead to Down syndrome, including a free trisomy 21 (94%), translocation (4%), and mosaicism (2%).
• A free trisomy 21 results from nondisjunction during meiosis in one of the parents. This occurrence is correlated with advanced maternal and paternal age.
  • The most common type of nondisjunction occurs in the maternal first meiotic division.
  • The percentage of errors during maternal second meiotic division is lower.
  • The incidence of nondisjunction in the first and second meiotic division of the paternal gametogenesis is nearly equal.
• Translocation may occur de novo or be transmitted by one of the parents.
  • Translocations are usually of the centric fusion type.
  • They frequently involve chromosome 14 (14/21 translocation), 21 (21/21 translocation), or 22 (22/21 translocation).
• Mosaicism is considered a postzygotic event (ie, following fertilization).
  • Two cell lines are found; one with a free trisomy, and the other with a normal karyotype.
  • This finding leads to patients with a great phenotypic variability, ranging from near normal to the classic trisomy 21 phenotype.
• Poor visual acuity in patients with Down syndrome may be due to degradation in optical quality and neurologic deficits.

Differential Diagnoses

Other Problems to Be Considered

Chromosome 21, mosaic 21 syndrome
Chromosome 21, translocation 21 syndrome
Trisomy G syndrome

Workup

Laboratory Studies

• Prenatal echography, amniocentesis, and fetal chromosome analysis are indicated. With prenatal echography, trisomy 21 may be diagnosed in the second and third trimester of pregnancy. The following prenatal echographic findings are suggestive of Down syndrome and may be followed with amniocentesis and fetal chromosome analysis:
  • Cystic hygroma colli
  • Cardiac defects
  • Duodenal obstruction
  • Hydrops fetalis
  • Prune belly anomaly
• Detection of carriers: When a translocation is detected in the parents, the risk of recurrence depends on the type of translocation and on the carrier parent's gender.

Imaging Studies

• Skull series show evidence of flattened facial features (including small or absent nasal bones), occiput, and brachycephaly.

Other Tests

• Postnatal medical tests include echocardiography.

Treatment

Medical Care

• A primary care provider should lead and coordinate the multisystemic evaluation of patients with Down syndrome. Awareness of systemic and ocular findings is essential for managing patients with trisomy 21.
• Medical therapy for blepharitis recommended for nonhandicapped patients is used for patients with Down syndrome. It includes lid scrubs and topical antibiotics. Treatment of blepharitis is of utmost importance prior to intraocular surgery.
• Indications used for eyeglass prescriptions for nonhandicapped patients are used for patients with Down syndrome. Glasses should be prescribed for patients at risk for amblyopia due to refractive errors, accommodative esotropia, aphakia, and pseudophakia.

Surgical Care

Surgical indications used for nonhandicapped patients are used for patients with Down syndrome. General anesthesia is advised during surgical intervention.

• Systemic surgery: Congenital cardiac malformations may require early cardiovascular surgery.
• Ocular surgery: Systemic evaluation, including a cardiovascular evaluation, is desirable prior to ophthalmic surgery.
• Patients may benefit from strabismus surgery.
• Corneal surgery
  • Patients with corneal pathologies may develop corneal hydrops and perforation.
  • Corneal transplants are indicated for severe scarring.
• Cataract surgery
  • Patients with Down syndrome have a high incidence of cataracts. Cataract extraction is indicated when decreased vision affects quality of life.
  • Extracapsular cataract extraction with intraocular lens implantation facilitates visual rehabilitation.
  • Phacoemulsification offers the advantage of a small incision.
• Ocular trauma
  • Traumatic ocular injuries are treated when required.
  • Patients with keratoglobus are at an increased risk of spontaneous corneal rupture following traumatic eye injuries.

Consultations

• Because of frequent congenital heart malformations, early cardiology consultation is desirable. Early cardiologic evaluation is crucial for diagnosing and treating congenital heart defects, which occur in up to 60% of these patients.
• Due to recurrent respiratory tract infections, a pediatric pneumologist should co-manage patients with Down syndrome.
• A child psychiatrist should lead liaison interventions, family therapies, and psychometric evaluations.
• Up to 10% of patients with Down syndrome have epilepsy; therefore, neurological evaluation may be needed.
• Genetic counseling is indicated.

Medication

Medical treatment of external eye diseases for patients with Down syndrome is the same as that for nonhandicapped patients.

In the medical treatment of glaucoma, avoid medications with cardiovascular and respiratory tract side effects.

Topical antibiotics

Used to treat chronic blepharitis.

Trimethoprim and polymyxin B sulfate (Polytrim) ophthalmic solution

Indicated for surface ocular bacterial infections (eg, bacterial conjunctivitis, blepharoconjunctivitis) caused by susceptible strains of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus viridans, Haemophilus influenzae, and Pseudomonas aeruginosa.

Dosing

Adult

Mild-to-moderate infections: 1 gtt in affected eye(s) q3h up to 10 d

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; viral, fungal, and mycobacterial infections of the eye

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use in deep ocular infections or in those likely to become systemic; prolonged use of antibiotics, or repeated therapy, may result in bacterial or fungal overgrowth of nonsusceptible organisms

Erythromycin (Ilotycin, E-mycin) ophthalmic ointment (0.5%)

Macrolide group of antibiotics that treats superficial ocular infections of the conjunctiva and/or cornea that are caused by erythromycin-susceptible organisms.

Dosing

Adult

Apply approximately 1 cm in length directly to infected eye(s) up to 6 times qd

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; viral, mycobacterial, fungal infections of eye; patients using steroid combinations after uncomplicated removal of a foreign body from cornea should also avoid using this product

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Do not use topical antibiotics to treat ocular infections that may become systemic; prolonged or repeated antibiotic therapy may result in bacterial or fungal overgrowth of nonsusceptible organisms and may lead to a secondary infection (take appropriate measures if superinfection occurs)

Glaucoma medications

Used to control intraocular pressure (IOP).

Brimonidine tartrate 2% (Alphagan) ophthalmic solution

Alpha-2 adrenergic receptor agonist, decreases IOP by a dual mechanism. Reduces aqueous humor production and increases uveoscleral outflow. Brimonidine tartrate has minimal effect on cardiovascular and pulmonary parameters.

Dosing

Adult

1 gtt in affected eye(s) q8h

Pediatric

Administer as in adults

Interactions

Coadministration with topical beta blockers may further decrease IOP; tricyclic antidepressants may decrease effects of brimonidine; CNS depressants such as barbiturates, opiates, and sedatives may potentiate effects of brimonidine

Contraindications

Documented hypersensitivity; MAO inhibitor therapy

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease, depression, cerebral or coronary insufficiency, orthostatic hypotension, Raynaud syndrome

Dorzolamide hydrochloride (Trusopt 2%) ophthalmic solution

Inhibitor of human carbonic anhydrase II. Affects ciliary processes of the eye and decreases aqueous humor secretion. Slows the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport, reducing IOP.

Dosing

Adult

1 gtt in affected eye(s) up to tid

Pediatric

Administer as in adults

Interactions

Coadministration with high-dose salicylate therapy may increase toxicity; may have additive systemic effects if patient is already on oral CA inhibitors

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Although administered topically, absorbed systemically; same types of adverse reactions that are attributable to sulfonamides may occur with topical administration of dorzolamide; local ocular adverse effects, primarily conjunctivitis and lid reactions, may occur with chronic administration of dorzolamide (discontinue therapy and evaluate patient before restarting therapy)

Brinzolamide 1% (Azopt) ophthalmic suspension

Inhibitor of carbonic anhydrase II. Following topical ocular administration, brinzolamide inhibits aqueous humor formation and decreases IOP. Indicated for elevated IOP in patients with ocular hypertension and open-angle glaucoma.

Dosing

Adult

1 gtt in affected eye(s) up to tid

Pediatric

Administer as in adults

Interactions

May have additive systemic effects if patient is already on oral CA inhibitors

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Same reactions that are attributable to sulfonamides may occur with topical brinzolamide administration; local ocular adverse effects, primarily conjunctivitis and lid reactions, may occur with chronic administration of dorzolamide (discontinue therapy and evaluate patient before restarting therapy)

Follow-up

Further Outpatient Care

• A pediatric ophthalmologist should evaluate patients in the first 6 months of life and annually thereafter if no eye pathology is present.

Inpatient & Outpatient Medications

• Indications for prescribing ophthalmic medications for patients with Down syndrome are the same as that for nonhandicapped patients.

Deterrence/Prevention

• Because of the high frequency of congenital heart defects, avoid medications, such as atropine, beta-blockers, dipivefrin, and epinephrine, that may lead to cardiovascular adverse effects.

Complications

• Complications are associated with the various clinical features of patients with trisomy 21. Cardiovascular and respiratory complications are the most frequent complications.
• Patients are susceptible to duodenal obstruction and leukemia.
• As with any patient undergoing eye surgery, complications can occur during the perioperative and postoperative periods.
  • Carefully monitor patients for bradycardia during strabismus surgery.
  • Watch for complications following penetrating keratoplasty (eg, wound dehiscence due to blunt trauma).
  • Help prevent wound dehiscence and postoperative infections by performing small incision cataract surgery and using postoperative shields.
• Prevent optical decentration in eyeglasses by examining the patient's pupillary distance (PD). Consider using monocular PD measurements as needed. Compare the patient's PD to the PD found in the eyeglasses. Consider advising the optician on the patient's dominant eye.

Prognosis

• Patients with Down syndrome have a shortened life expectancy. Early evaluation, diagnosis, and intervention may prevent deaths due to congenital heart defects.
• Mental retardation is common in patients with trisomy 21; however, patients with mosaicism tend to have higher IQs.

Patient Education

• Early stimulation therapy may benefit patients with Down syndrome.
• Patients benefit from special education programs. Psychometric studies and social worker intervention are needed for special education planning.
• Risk of recurrence for the patient's child is 50%.
• For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Down Syndrome.

Miscellaneous

Medicolegal Pitfalls

• Maintain open communication with primary care providers, legal guardians, and caretakers. Carefully explain and ensure that they understand potential surgical complications. Obtain complete preoperative informed consent.

Special Concerns

• Support groups for patients with Down syndrome include the following:
  • National Down Syndrome Congress
    1370 Center Drive, Suite 102
    Atlanta, GA 30338
    (800) 232-NDSC (6372)
  • National Down Syndrome Society
    666 Broadway, Suite 800
    New York, NY 10012
    (800) 221-4602

References

1. Berk AT, Saatci AO, Ercal MD, Tunc M, Ergin M. Ocular findings in 55 patients with Downs syndrome. Ophthalmic Genet. Mar 1996;17(1):15-9. [Medline].

2. Caputo AR, Wagner RS, Reynolds DR, Guo SQ, Goel AK. Down syndrome. Clinical review of ocular features. Clin Pediatr (Phila). Aug 1989;28(8):355-8. [Medline].

3. Copin H, Bremond-Gignac D. Ocular manifestations of Down syndrome and cytogenic aspects. J Fr Ophtalmol. Oct 2004;27(8):958-9. [Medline].

4. da Cunha RP, Moreira JB. Ocular findings in Downs syndrome. Am J Ophthalmol. Aug 1996;122(2):236-44. [Medline].

5. Frantz JM, Insler MS, Hagenah M, McDonald MB, Kaufman HE. Penetrating keratoplasty for keratoconus in Downs syndrome. Am J Ophthalmol. Feb 15 1990;109(2):143-7. [Medline].

6. Goto S, Yo M, Hayashi T. Intraocular lens implantation in severely mentally and physically handicapped patients. Jpn J Ophthalmol. 1995;39(2):187-92. [Medline].

7. Haddow JE, Palomaki GE, Knight GJ, Williams J, Pulkkinen A, Canick JA, et al. Prenatal screening for Downs syndrome with use of maternal serum markers. N Engl J Med. Aug 27 1992;327(9):588-93. [Medline].

8. Jaeger EA. Ocular findings in Downs syndrome. Trans Am Ophthalmol Soc. 1980;78:808-45. [Medline].

9. Little JA, Woodhouse JM, Lauritzen JS, Saunders KJ. The impact of optical factors on resolution acuity in children with Down syndrome. Invest Ophthalmol Vis Sci. Sep 2007;48(9):3995-4001. [Medline].

10. Roizen NJ, Mets MB, Blondis TA. Ophthalmic disorders in children with Down syndrome. Dev Med Child Neurol. Jul 1994;36(7):594-600. [Medline].

11. Shapiro MB, France TD. The ocular features of Downs syndrome. Am J Ophthalmol. Jun 15 1985;99(6):659-63. [Medline].

12. Volker-Dieben HJ, Odenthal MT, DAmaro J, Kruit PJ. Surgical treatment of corneal pathology in patients with Downs syndrome. J Intellect Disabil Res. Apr 1993;37 (Pt 2):169-75. [Medline].

Keywords

Down's syndrome, mongolism, trisomy 21, trisomy of chromosome 21

Contributor Information and Disclosures

Author

Natalio J Izquierdo, MD, Associate Professor, Department of Ophthalmology, Medical Sciences Campus, University of Puerto Rico
Natalio J Izquierdo, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, International Society for Genetic Eye Diseases and Retinoblastoma, Pan-American Association of Ophthalmology, and Sociedad Puertorriquena de Oftalmologia
Disclosure: Nothing to disclose.

Coauthor(s)

William Townsend, MD, Professor and Director, Department of Pediatric Surgery, Section of Ophthalmology, University Pediatric Hospital, Puerto Rico Medical Center
Disclosure: Nothing to disclose.

Medical Editor

Gerhard W Cibis, MD, Clinical Professor, Director of Pediatric Ophthalmology Service, Department of Ophthalmology, University of Kansas, Kansas City
Gerhard W Cibis, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, and American Ophthalmological Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Managing Editor

J James Rowsey, MD, Former Director of Corneal Services, St Luke's Cataract and Laser Institute, Florida
J James Rowsey, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for the Advancement of Science, American Medical Association, Association for Research in Vision and Ophthalmology, Florida Medical Association, Pan-American Association of Ophthalmology, Sigma Xi, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

To Irene H. Maumenee, MD, professor of ophthalmology, a great leader who teaches young ophthalmologists how to provide excellent eye care to patients with hereditary eye diseases throughout the world.

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