S E C T I O N
10 Skeletal Disorders
102 DOWN SYNDROME 758.0
(Trisomy 21)
Natalio J. Izquierdo, MD
San Juan, Puerto Rico
ETIOLOGY/INCIDENCE
Various chromosomal abnormalities may lead to the Down syndrome including: a free trisomy 21 (94% of patients), translocation (4% of patients), and mosaicism (2% of patients).
●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 (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.
Occurrence strongly depends on 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. For mothers aged 45 years or older, the occurrence is 1 per 55 live births.The risk for recurrence of Down syndrome in a patient’s siblings is also related to maternal age.
Down syndrome occurs once in every 600–700 live births in the United States and Japanese populations.
COURSE/PROGNOSIS
A primary care provider should lead and coordinate the multisystemic evaluation of patients with Down syndrome. Aware-
ness of systemic and ocular findings is essential for managing patients with trisomy 21.
●Because of frequent congenital heart malformations, which occur in up to 60% of these patients, early cardiology consultation is desirable.
●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. Mental retardation is common in patients with trisomy 21; however, patients with mosaicism tend to have higher IQs.
●Up to 10% of patients with Down syndrome have epilepsy; therefore, neurological evaluation may be needed.
●Genetic counseling is indicated.
●Ophthalmic medical care for blepharitis, refractive errors, strabismus, corneal ectasias and cataracts is needed.
●Ophthalmic surgical indications used for non-handicapped patients are used for patients with Down syndrome. General anesthesia is desirable for patients with the syndrome who undergo surgery.
Patients with Down syndrome have a shortened life expectancy. Early evaluation, diagnosis and intervention may prevent deaths due to congenital heart defects.
DIAGNOSIS
Clinical signs and symptoms
Eight or more of the characteristic clinical findings lead to a definite diagnosis. In doubtful cases, chromosomal analysis may be necessary.
●General physical features in patients with Down syndrome include shortened extremities, short limbs, short and broad hands, short fifth middle phalanx, simian palmar creases, joint hyperextensibility or hyperflexibility, neuromuscular hypotonia, dry skin, premature aging, a wide range of intelligence quotients and congenital heart defects.
●Patients with the 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, higharched palate, dental abnormalities, and a short and broad neck.
●Ocular signs in patients with the Down syndrome include:
●Lid anomalies such as prominent epicanthal folds, upward slanting of the palpebral fissures and congenital ectropion (rare) occur;
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Disorders Skeletal • 10 SECTION
●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;
●Nasolacrimal duct obstruction;
●Amblyopia associated to strabismus, refractive errors, or media opacities;
●Strabismus occurs in up to 20% of patients;
●Evaluate corneas carefully for keratoconus or keratoglobus. Scissoring of the retinoscopic reflex is an early finding in patients with keratoconus. Use Placido disks, keratometers, or topographies to evaluate patients with Down syndrome who have keratoconus. Rizzuti and Munson signs appear later;
●Up to 90% of patients with the syndrome may have iris’ Brushfield spots. These spots are focal areas of iris stromal hyperplasia, surrounded by relative hypoplasia. These are more common in patients with lightly pigmented irides;
●Cataracts occur in patients with the syndrome. Lens opacities may be sutural, zonular, or complete. These may be congenital or may occur later in life;
●Glaucoma usually appears during infancy. Therefore, patients must be examined for corneal edema, megalocornea, increased intraocular pressure, progressive myopia, and optic nerve cupping;
●Retinal findings include: an increased number of retinal vessels crossing the disk margin, and retinal detachments;
●Cystic hygroma colli;
●Cardiac defects;
●Duodenal obstruction;
●Hydrops fetalis;
●Prune belly anomaly.
Craniofacial radiographic findings in children with the syndrome may include: flattened facial features (including small or absent nasal bones), occiput, and brachycephaly.
Echocardiography is advisable in patients with the syndrome.
TREATMENT
Medical
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 includes lid scrubs and topical antibiotics.
●Indications used for eyeglass prescription in nonhandicapped patients are used for patients with the syndrome. Glasses should be prescribed for patients at risk for amblyopia due to refractive errors, accommodative esotropia, aphakia, and pseudophakia.
Surgical
Surgical indications used for nonhandicapped patients are used
●Patients with the syndrome may have refractive errors. for patients with the syndrome. General anesthesia is advisable
(Figure 102.1)
Laboratory findings
Previous studies discuss the benefits of amniocentesis during pregnancy in mothers with low α-fetoprotein serum values during the beginning of the second trimester.
Further, trisomy 21 may be diagnosed in the second and third trimester of pregnancy using prenatal echography. The following prenatal echographic findings are suggestive of Down syndrome and may be followed with amniocentesis and fetal chromosome analysis:
during surgical interventions.
●Systemic surgery: patients with congenital cardiac malformations as part of the syndrome may require early cardiovascular surgery.
●Ocular surgery: systemic evaluation, including a cardiovascular evaluation, is desirable prior to eye surgery.
●Patients with strabismus as part of the Down syndrome may benefit from strabismus surgery.
●Patients with corneal pathologies as part of the syndrome may develop corneal hydrops and perforation. Corneal transplants are indicated for severe scarring.
●Patients with trisomy 21 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.
●Patients with the syndrome who develop keratoglobus are at increased risk of traumatic eye injuries. Traumatic ocular injuries are treated when required.
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FIGURE 102.1. Cataract in patient with Down syndrome. |
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