Down syndrome

George T Capone MD (Dr. Capone of the Johns Hopkins University and Director of the Down Syndrome Clinic at Kennedy Krieger Institute received a research grant from LuMind and an hororaium from Roche for serving on an advisory board.)
Michael V Johnston MD, editor. (Dr. Johnston of Johns Hopkins University School of Medicine and Chief Medical Officer at Kennedy Krieger Institute has no relevant financial relationships to disclose.)
Originally released October 29, 1995; last updated May 12, 2016; expires May 12, 2019

This article includes discussion of Down syndrome, Down's syndrome, Downs syndrome, trisomy 21, trisomy 21 mosaicism, and chromosome 21 translocation. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

In addition to congenital birth defects, persons with Down syndrome are at risk for acquired medical conditions during childhood, throughout adulthood, as well as premature onset of aging-related conditions beginning in the 3rd to 4th decades of life. Some of the comorbid medical conditions associated with Down syndrome have atypical presentations that require a high index of suspicion for diagnosis. Healthcare guidelines for persons with Down syndrome are designed to detect occult conditions in asymptomatic individuals and to guide physicians evaluating medically complex or difficult-to-diagnose patients. Successful recognition and treatment of medical conditions is paramount to managing patients with decline in functional skills.

Key points

 

• Lower cervical spondylosis with osteophytes and disc herniation increases with age and may pose more of a neurologic threat in persons of advanced age than atlantoaxial instability.

 

• The most significant medical disorders related to mortality are dementia, declining motor function, epilepsy, and respiratory infections.

Historical note and terminology

The first comprehensive description of this condition was provided by Dr. John Langdon Down in 1866.

Image: Dr. John Langdon Down
Down served as Superintendent of the Earlswood Asylum for Idiots in Surrey, England from 1858 to 1868 and had ample opportunity to observe and examine large numbers of individuals with mental retardation. Influenced by the evolutionary teachings of that period, his intellectual pursuits led him to propose an ethnic classification of "congenital idiocy," based on physiognomy and racial stereotypes (Down 1866). In his classification, he proposed 5 different varieties: (1) Caucasian, (2) Malaysian, (3) Ethiopian, (4) American-native, and (5) Mongolian. He called special attention to the Mongolian group because he was struck by their close physical and mental resemblance to one another. In his report of 1866, Down highlighted some of the salient aspects of the physical appearance and behavioral attributes of individuals with this syndrome. He also speculated, incorrectly, that the condition was caused by tuberculosis in the parents. Although his ethnic classification scheme was never accepted by his medical peers, Down's major contribution was to distinguish this condition from congenital hypothyroidism, or "cretinism," which was also prevalent at that time.

Also writing in 1866, Seguin apparently described persons with Down syndrome but refers to them as having a subtype of cretinism called "furfuraceous cretinism" (Seguin 1866). By 1877, Ireland clearly delineated between the 2 conditions and distinguished the "Mongolian idiot" from the "cretinoid idiot" (Ireland 1877). The first illustrations in the medical literature of an individual with Down syndrome appeared in 1876 in a classic paper by Fraser and Mitchell, in which they provided marvelous illustrations of the face, foot, and skull (Fraser and Mitchell 1876).

Image: Down syndrome patient (early illustration)
Image: Down syndrome patient (early illustration of face, foot, and skull)
They were also the first to publish a pathologic description of the brain at autopsy.
Image: Down syndrome patient (early illustration of brain)
Apparently unaware of Langdon Down's paper 10 years earlier, Fraser and Mitchell also called attention to the oriental-like appearance of the condition and proposed the term "Kalmuk idiocy" after the Mongolians (Kalmuk) who migrated into the lower Voltar region of Russia. Fortunately, this term was never accepted by the medical community. The term "Mongolian idiocy," or "Mongolism," was used widely throughout the latter part of the 19th and first half of the 20th century. The chromosomal etiology (trisomy 21) for Down syndrome has been known since 1959 (Lejeune et al 1959). In 1961, sparked by the discovery 2 years earlier of trisomy 21 in persons with Down syndrome as well as by complaints from Chinese and Japanese scientific investigators, it was proposed that the term "Down syndrome" or "trisomy 21" be adopted to replace the inaccurate and anachronistic designation "Mongolism" (Allen et al 1961). The complete DNA sequence of human chromosome 21 (long-arm) was determined in 2000 and is revolutionizing our genetic understanding of this condition (Gardiner 2000; Hattori 2000).

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