eMedicine Specialties > Dermatology > Pediatric Diseases

Down Syndrome

Author: Assen L Dourmishev, MD, PhD, DSc, Professor of Dermatology, Consultant Dermatologist, Department of Dermatology, Medical Institute of the Ministry of Internal Affairs
Coauthor(s): Camila K Janniger, MD, Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, New Jersey Medical School
Contributor Information and Disclosures

Updated: Jul 1, 2009

Introduction

Background

Down syndrome is a frequent form of mental retardation associated with characteristic morphologic features (mongolism) and many somatic abnormalities due to a number of chromosomal aberrations.

The characteristic clinical features that discriminate the syndrome from other mental deficiencies were first described by John Langdon Down¹ in 1866. The condition has typical physical features and multisystem anomalies, some of which are dermatologic. The skin lesions in this syndrome were noted by Seguin (1846), who spoke of d'idiots furfuraces. Certain dermatoglyphic features in Down syndrome that differed from control subjects were pointed out in 1939. In 1959, a chromosomal abnormality was proven to cause Down syndrome.²

Other eMedicine articles on Down syndrome are Down Syndrome (ophthalmology), Down Syndrome (pediatrics), Down Syndrome, Postnatal Findings (radiology), and Down Syndrome, Prenatal Findings (radiology).

Pathophysiology

Three cytogenetic variants cause Down syndrome: trisomy 21, chromosomal translocation, and mosaicism.

Trisomy 21 accounts for nearly 95% of all patients with Down syndrome. Most of the remaining patients have 46 chromosomes with translation of the long arm of an extra number 21 either to a D group or to another G group chromosome. As a woman ages, her risk of giving birth to a child with Down syndrome increases. This is of particular concern for women older than 35 years.

Less commonly, patients with Down syndrome may have 46 chromosomes with either 21/22 translocation or 21/21 translocation.

A few patients have mosaicism with a normal cell line, usually milder physical stigmata, and impaired intelligence.

Two different hypotheses have been proposed to explain the mechanism of gene action in Down syndrome: developmental instability (loss of chromosomal balance) and "gene dosage effect".³ According to the gene dosage effect hypothesis, the genes located on chromosome 21 have been overexpressed in cells and tissues of Down syndrome patients, and this contributes to the phenotypic abnormalities.⁴

Pertinent guidelines from the American College of Obstetricians and Gynecologists are Screening for fetal chromosomal abnormalities.⁵

Frequency

United States

The frequency is 1 case in 800 live births or approximately 6000 children per year.

International

Down syndrome is the most common autosomal abnormality and occurs in approximately 1 case per 700 live births. Down syndrome accounts for about one third of all moderate and severe mental handicaps in school-aged children.

Mortality/Morbidity

• Approximately 25-30% of patients with Down syndrome die during the first year of life. The most frequent causes of death are respiratory infections (bronchopneumonia) and congenital heart disease.
• The life expectancy of patients with Down syndrome is slightly reduced.

Race

Down syndrome has been reported in people of all races.

Sex

Both sexes are affected equally. The sexual incidence of patients with Down syndrome is the same. Males with Down syndrome are sterile. In the few affected females who have had children, about one half of the offspring have been affected.

Age

Characteristic morphologic features of mongolism can be recognized immediately at birth, but they are obvious in children older than 1 year. Some dermatologic features increase with advancing age.

Clinical

History

The major features of Down syndrome are as follows:

• Mental retardation - Mild to severe, intelligence quotient (IQ) of 25-50, constant feature
• Characteristic head appearance - Small head (brachycephaly), flat facies with increased interocular distance (hypertelorism), depressed nasal bridge, flat occiput, and broad short neck

• Ocular anomalies⁶ - Narrow and upward and outward slating of the rima palpebrarum (80%), white Brushfield spots arranged in concentric rings on the periphery of the iris (60%), medial epicanthal folds, keratoconus, strabismus, cataracta (2%), and retinal detachment
• Oral features - Small mouth (relatively) with protrusion of the tongue (macroglossia) and difficulty in eating and speaking, scrotal tongue, hypoplasia of the maxilla, delayed tooth eruption, hypodontia, juvenile periodontitis, and cleft lip or palate (rare)

• Anomalous auricles - Small ears with anomalies of the folds

• Skeletal anomalies - Short stature (below normal height); broad, short hands, feet, and digits; short curved fifth finger (dysplasia of the mid phalanx), clinodactyly of the fifth finger; dysplasia of the pelvis (shallow acetabular angle with small iliac wings); joint laxity; a wide gap between the first and second toes; and atlantooccipital instability

• Muscle hypotonia in newborns with decreased response to normal stimuli
• Protuberant abdomen (with or without an umbilical hernia)

• Hypogenitalism (small penis, scrotum, and testes), hypospadia, cryptorchism, and delayed and incomplete puberty (often)
• Congenital defects - Heart or endocardial cushion defects (40%), duodenal atresia, Hirschsprung disease, polydactylia, and syndactylia
• Excess skin on the back of the neck
• Others - Recurrent respiratory infections, leukemia (1%),⁷ epilepsy (10%), hypothyroidism (3%), and presenile dementia (development of Alzheimer disease after age 40 y)
• Cutaneous manifestations of Down syndrome include the following:
  • Soft and velvety skin in early childhood
  • Dry skin in late childhood - Xerosis (70%), atopic dermatitis (50%), palmoplantar hyperkeratosis (40-75%), and seborrheic dermatitis (31%)
  • Premature wrinkling of the skin, cutis marmorata, and acrocyanosis
  • Bacteria infections, fungal infections (tinea), and ectoparasitism (scabies)
  • Elastosis perforans serpiginosa⁸
  • Syringomas
  • Alopecia areata (6-8.9%)
  • Vitiligo
  • Angular cheilitis

Physical

• Analysis of fingerprints can be of value in selecting patients for cytogenetic analysis.  Specifically, children with Down syndrome have a high incidence of loops and a low incidence of whorls.⁹ The presence of a Mongolian crease is also commonly associated with Down syndrome.
• Xerosis, atopic dermatitis, secondary lichenification, seborrheic dermatitis, and ichthyosiform changes are more frequent in childhood. Children with Down syndrome have dry skin in early childhood. By age 15 years, more than 70% show generalized xerosis of a mild-to-moderate degree.
• Atopic dermatitis is present in more than 50% of patients in childhood. Its course is often complicated by lichenification and impetiginization, most likely caused by an increased susceptibility to infections.
• Patchy lichenification is present in approximately 30% of patients younger than 10 years and in more than 80% of patients older than 20 years. This condition resembles lichen simplex and usually occurs on the upper arms, the wrists, the anterior part of the thighs, the posterior part of the auricles, and the posterior part of the neck. Seborrheic dermatitis and ichthyosiform changes have also been described.
• Palmoplantar hyperkeratosis is not seen before the age of 5 months, but its incidence rose to 75% in children aged 5 years and older with normal vitamin A levels. A transverse palmar crease (simian crease) is seen in 40-50% of these patients.

• Oral lesions of Down syndrome (fissured and geographic tongue, macroglossia, juvenile periodontitis) are frequent manifestations of the disease. Fissuring and thickening of the lips and angular cheilitis are frequent and increase in incidence and severity with age. Cheilitis occurs with greater frequency in children with Down syndrome than in unaffected persons. It is explained by mechanical factors, trauma, actinic influence, atopy, avitaminosis, or low-grade infections (candidiasis).
• A fissured tongue (plicated or scrotal) occurs in as many as 80% of children with Down syndrome, but it affects about 5% of the general population. It is often associated with macroglossia. The cause of this condition is unclear. Geographic tongue occurs in 11.3% of patients with Down syndrome. Juvenile periodontitis is a feature of Down syndrome, and its incidence among the various age groups parallels the occurrence of cheilitis but without significant correlation.
• Baby hair is normal at birth but often is fine and hypopigmented.
• The incidence of alopecia areata is higher than in dermatologic outpatients or in individuals with mental retardation. It occurs in 6-8.9% of patients with Down syndrome. The disorder tends to be more severe, extensive, and persistent than in otherwise healthy patients with the condition. A decrease in the T-cell–dependent immune response and immunoglobulin G (IgG) deficiencies is reported in patients.
• In an Iranian study of 100 children with Down syndrome, skin or mucosal  findings were noted in 61. These included fissured tongue 28%, geographic tongue 4%, hypertrophy of tongue papilla 22%, cheilitis 13%, premature graying 14%, alopecia areata 11%, keratosis pilaris 4%, trichotillomania 4%, xerosis 12%, palmoplantar hyperkeratosis 10%, seborrheic dermatitis 3%, syringoma 6%, vitiligo 3%, and livedo reticularis in 2% of the patients.¹⁰ Note that atopic dermatitis is uncommon is this particular population.
• The skin ages prematurely, showing lentigines and atrophy.
• Vascular instability (acrocyanosis and cutis marmorata) is a frequent cutaneous manifestation of disease because peripheral circulation is poor and an increased incidence of congenital heart disease occurs. Cutis marmorata of the trunk and the extremities is observed in 12.7% of children with Down syndrome.
• Systemic lupus erythematosus has been observed in patients with Down syndrome,¹¹ but the association is not convincing.
• Psoriasis runs a normal course in patients with Down syndrome, though a widespread, extremely hyperkeratotic form with lesions in unusual sites is observed.
• Carotenemia is no more frequent in patients with Down syndrome than in other persons with mental retardation. The incidence is increased in patients with associated hypothyroidism. Communal living, which often results in a diet rich in carotene products, is a reason for this condition.
• Calcinosis cutis associated with milialike syringomas is observed in patients with Down syndrome with transepithelial elimination of calcium from tumors.
• Unusual forms of elastosis perforans serpiginosa are noted in patients with Down syndrome. The onset of skin lesions is during the second decade of life. Both sexes are affected, with an increased prevalence in males. The male-to-female ratio is 4:1. Cutaneous lesions are more extensive, and the duration of the condition is longer, 10 years or more versus 5 years in the idiopathic type. Keratotic papules often coalescence to form an arcuate or serpiginous pattern. Lesions heal with atrophic scars.
• A variety of bacterial infections, fungi, or ectoparasite infestations afflict patients with Down syndrome. Cutaneous bacterial infections (eg, angular cheilitis, folliculitis, furuncles, abscesses, secondary impetigo) are common in patients with or without atopic dermatitis.
• Dermatophytic infections frequently occur in postpubertal patients with Down syndrome who are institutionalized. The high prevalence of tinea pedis (>50%) and an increased incidence of severe onychomycosis in young adults result from communal living.
• Pityrosporum folliculitis, a chronic persistent erythematous follicular papular eruption affecting the presternal and infrascapular region, is found in about 50% of men aged 20-40 years with Down syndrome, but it is uncommon in women with Down syndrome.
• Children with Down syndrome are predisposed to the development of crusted (Norwegian) scabies. The reasons for this propensity are unclear. Patients have generalized erosions, scaling, and hyperkeratotic crusted plaques, especially on the flexural aspects of the wrists, the buttocks, and the sacrum. Nails are deformed, with marked subungual hyperkeratosis. Patients have an immunologic dysfunction; the cause is related to a poor cutaneous sensation, leading to a diminished likelihood of mites being mechanically removed.
• The tumor profile of patients with Down syndrome is different from that of other people. Syringomas occur more often in patients with Down syndrome than in other patients. These benign appendiceal tumors are observed in 18.5-39% of patients with this disease. Females are affected more than twice as often as males. Lesions are usually limited to regions around the eyes, but disseminated syringomas are also observed. The presence of tumors is not related to IQ or any other manifestation of the disorder.
• Leukemia (acute and subacute) is 3 times more common in children with Down syndrome than in children without the disease. Leukemia cutis is also observed in these patients. Congenital leukemia and leukemoid reactions,¹² which are highly associated with trisomy 21, are difficult to distinguish on clinical and histologic grounds. Recognition of a transient form of congenital leukemia is important for the treatment of such patients.

Causes

• Three cytogenic variants cause Down syndrome.
  • Trisomy 21
  • Chromosomal translocation
  • Mosaicism
• The incidence of this syndrome at various maternal ages is as follows:
  • 15-29 years - 1 case in 1500 live births
  • 30-34 years - 1 case in 800 live births
  • 35-39 years - 1 case in 270 live births
  • 40-44 years - 1 case in 100 live births
  • Older than 45 years - 1 case in 50 live births
• On rare occasions, the disease can be observed in a few members of a family.

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