Author: Vanessa Ngan, Staff Writer, 2006. Updated by Dr Arun Gangakhedkar, Paediatrician, Waitemata District Board, Auckland. DermNet NZ Editor in Chief: Adjunct A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. October 2018.
Down syndrome is a common genetic disorder resulting from the chromosomal abnormality, Trisomy 21. Individuals with Down syndrome have a cognitive delay and characteristic appearances associated with certain medical conditions [1–8].
Down syndrome incidence rises with advancing maternal age, but most are born to younger mothers under 30 years owing to a greater number of pregnancies in this age group. Due to an increase in the terminations of pregnancies with Down syndrome, the live birth prevalence decreased from one in 700 to about one in 1000 in New Zealand.
Studies suggest marginally higher rates of Down syndrome in boys than girls.
A cell division error during early conception results in three copies of chromosome 21 instead of the usual two. The chromosomal abnormality results from a lack of normal separation (non-disjunction) during cell division as the pair of chromosomes in either the sperm or egg fail to separate. This results in a gain of an additional chromosome 21 and the occurrence of Down syndrome [1–8].
The clinical phenotype in all types of Down syndrome is similar, with subtle differences in mosaic Down syndrome which depends on the extent of the trisomy 21 cell population.
The diagnosis is suspected or confirmed in the neonatal period in most infants with Down syndrome. Characteristic physical features of Down syndrome include [1–8]:
Red cell macrocytosis and polycythaemia may affect up to two-thirds of infants. Transient myeloproliferative disorder (TMD) may be present in up to 10% of newborns with Down syndrome. Acute leukaemias are reported in 1 in 300 individuals with Down syndrome.
A single transverse palmar crease is the main cutaneous phenotype and is easily detectable. However, a single transverse palmar crease may also occur as a normal variant that is unilateral in 4% and bilateral in 1% of general population [9–18].
Other cutaneous features include dry skin and a large tongue with a scrotal appearance.
A variety of dermatological disorders are more common in Down syndrome due to combination of immune and genetic dysregulation and inefficient physiological processes.
Defective regulation of genes located on chromosome 21 may play a role in keratosis pilaris, alopecia areata, and vitiligo. Immune dysregulation leads to increased susceptibility to bacterial and fungal skin infections.
Transient physiological cutaneous manifestations are common during infancy, and chronic skin conditions appear with age.
Acrocyanosis is due to poor peripheral circulation and is more pronounced in Down syndrome. It is commonly observed in newborns.
Cutis marmorata is a lacy mottled skin discoloration common during early infancy due to altered blood flow in the small blood vessels of the skin. Discolouration is most marked in the skin exposed to cooler environmental temperatures.
The skin change due to livedo reticularis is similar but less marked than cutis marmorata. It mostly affects the lower limbs but may also be present on the arms and trunk. Livedo reticularis becomes more pronounced in cold weather.
Signs of premature ageing reported in Down syndrome include greying or thinning of the hair, skin atrophy, early development of rhytids (wrinkles) and lentigines. The overexpression of the SOD gene, which regulates free radical metabolism, is located on chromosome 21, and is overexpressed as a result of trisomy 21. This leads to excess production of hydrogen peroxide, causing release of cytotoxic hydroxyl radicals. This in turn causes cell membrane lipid oxidation, altering the structure and function of the skin and involved tissues.
The skin texture is soft and velvety in newborn infants with Down syndrome in comparison to unaffected infants. The skin becomes rough with altered texture through the school years with most adolescents and adults showing chronic skin changes [9–18].
Chronic skin conditions associated with Down syndrome may be related to immune insufficiency; autoimmune processes; infections and infestation-related complications; and defects of keratinisation or connective tissue.
The skin becomes increasingly dry, rough and inelastic and there is patchy lichenification with increasing age.
A clinical diagnosis of Down syndrome is always confirmed by cytogenetic analysis. A standard or conventional karyotype should be requested. A rapid FISH (fluorescent in-situ hybridisation) analysis for trisomy 21 should be specified on the laboratory request form when an urgent result is required.
Post-term, a diagnosis of Down syndrome can be made from identification of characteristic phenotypic features, but clinical diagnosis is not always possible in patients with mosaic Down syndrome.
Genetic disorders such as Smith-Magenis syndrome, Zelleweger syndrome and Beckwith-Weidemann syndrome may be confused for Down syndrome as these syndromes present with similar phenotypic features in early infancy.
Careful skin examination is required as dermatological problems are reported in up to 87% of individuals with Down syndrome.
Managing skin and associated medical conditions is important for providing optimal medical care for individuals with Down syndrome.
Other related support services should include:
Most skin conditions may be managed with optimal care and supervision.
Longevity in Down syndrome is influenced by the severity of congenital abnormalities or associated medical problems. Substantial improvements in the life span are observed with better health surveillance and management compared to a few decades ago.
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