Smith-Magenis syndrome (SMS) is a rare genetic disorder that impacts various aspects of development. It is a condition individuals are born with, affecting multiple body systems. SMS is also considered a developmental disorder that influences behavior, emotions, and learning processes.
Understanding Smith-Magenis Syndrome
Smith-Magenis syndrome is a complex, multi-system developmental disorder, affecting an estimated 1 in 15,000 to 1 in 25,000 individuals. This condition is characterized by a combination of physical, developmental, and behavioral features that can vary in severity. Individuals with SMS experience a wide range of symptoms, including intellectual disability, distinct facial features, and sleep disturbances.
The syndrome is a lifelong condition, meaning its characteristics will be present throughout an individual’s life. While specific manifestations differ, the overarching impact on cognitive development, physical appearance, and behavior remains consistent.
Key Facial Features
Individuals with Smith-Magenis syndrome often present with a recognizable set of facial features. The overall facial shape is typically broad and square, often accompanied by full cheeks and a prominent lower jaw.
The forehead is commonly prominent, with heavy brows. Eyes often appear deep-set and can be close together. The middle of the face, or midface, may appear flattened or underdeveloped, a condition known as midface hypoplasia.
The nose has a broad nasal bridge and a reduced nasal height. In younger individuals, the nose bridge might appear scooped, evolving into a more “ski-jump” shape with age. The tip of the nose is often full.
The mouth is typically wide with full upper and lower lips. The upper lip often has a “tented” or “cupid’s bow” appearance, with a fleshy and everted central portion and bulky philtral pillars. The corners of the mouth may turn downwards.
How Facial Features Evolve
The facial characteristics associated with Smith-Magenis syndrome often change and become more pronounced as an individual ages. In infancy, the face may be described as “doll-like” or cherubic, with some features being subtle. As children grow into middle childhood and adulthood, these features become more distinctive and recognizable.
Mandibular growth tends to exceed maxillary growth after mid-childhood, leading to increased jaw width and protrusion, and a more pronounced midface hypoplasia. The deepening of the eyes and changes in the overall facial proportions become more apparent in older individuals.
The Genetic Cause
Smith-Magenis syndrome is caused by a genetic alteration involving chromosome 17. The most common cause is a small deletion of genetic material from a specific region on the short arm of chromosome 17, known as 17p11.2. This deletion typically occurs spontaneously during the formation of reproductive cells or early fetal development and is generally not inherited.
This deleted region contains multiple genes, but the loss of the retinoic acid-induced 1 (RAI1) gene is primarily responsible for most characteristic features of SMS. The RAI1 gene plays a role in regulating the expression of other genes, including those involved in circadian rhythm. In the remaining cases, SMS can result from a mutation within the RAI1 gene itself, rather than a deletion of the chromosomal segment.