Down Syndrome

Introduction

• Description: Down syndrome is characterized by physical and mental symptoms that have their origin in the presence of extra genetic material from chromosome 21. This may be because of duplication or translocation errors of genetic material that result in effective duplication. Patients with Down syndrome exhibit a spectrum of changes that range from mild to profound.

• Prevalence: Based on maternal age, from approximately 1/1250 at the age of 25 years to approximately 1/100 at the age of 40 years. The most common chromosome abnormality among liveborn infants.

• Predominant Age: Most patients with Down syndrome are identified at birth. Their life span is generally shorter than average (usually 50–60 years).

• Genetics: 90% are caused by nondisjunction, resulting in an extra chromosome 21, 5% are caused by translocation, and 5% are caused by mosaicism.

Etiology and Pathogenesis

• Causes: Nondisjunction of chromosome 21, resulting in two copies from one parent and one from the other, with a net total of three. Balanced translocation of chromosome 21q material onto another chromosome (most often 12, 13, or 15) in 90% of patients. During cell division, this is independently inherited from the normal chromosome 21s, resulting in extra genetic material. Approximately half of these duplications are new occurrences, and half have a parental carrier. Mosaicism of two cell lines: one normal and one with trisomy 21. This is generally associated with milder clinical manifestations.

• Risk Factors: Maternal age, known carrier state (translocation), prior chromosomal abnormality. Screening based on age identifies only 25% of all cases (the remainder are born to mothers considered to be at low risk).

Signs and Symptoms

• Brachycephaly (100%)

• Hypotonia at birth (80%)

• Posterior third fontanel

• Anomalous, small or low-set ears

• Prominent epicanthal folds (90%)

• Enlarged tongue (75%)

• Depressed nasal bridge

• Cardiac murmur (50%)

• Cognitive impairment (IQ 40–345)

• Abnormal dermatoglyphics (single palmar crease, absent plantar whorl)

Diagnostic Approach