Smith-Magenis Syndrome Flashcards
A 5-year-old boy is brought to the pediatric clinic by his parents due to concerns about his behavior and developmental delays. The parents report frequent temper tantrums, self-hugging, and biting his hands when frustrated. He has a history of sleep disturbances with difficulty falling asleep and waking frequently during the night. Physical examination reveals a broad, square-shaped face, deep-set eyes, and brachydactyly. His developmental milestones are significantly delayed, particularly in speech. Genetic testing reveals a deletion on chromosome 17p11.2.
What is the most likely diagnosis, and which of the following is the best initial management for his sleep disturbances?
A. Noonan syndrome; growth hormone therapy
B. Smith-Magenis syndrome; melatonin supplementation
C. Williams syndrome; dietary restriction of calcium and vitamin D
D. Down syndrome; behavioral therapy
E. Angelman syndrome; benzodiazepines for sleep
Correct Answer: Smith-Magenis syndrome; melatonin supplementation
Explanation: Smith-Magenis syndrome is caused by a deletion on chromosome 17p11.2 or mutations in the RAI1 gene. It is characterized by distinctive facial features (broad, square-shaped face, deep-set eyes), mild to moderate intellectual disability, self-injurious behaviors, and sleep disturbances. Sleep issues are due to an inverted circadian rhythm of melatonin secretion, where melatonin levels are elevated during the day and reduced at night. The best management for sleep disturbances is melatonin supplementation in the evening to correct the melatonin rhythm and improve sleep quality.
Incorrect Answers:
A. Noonan syndrome; growth hormone therapy: Noonan syndrome is associated with short stature, webbed neck, and cardiac defects like pulmonary stenosis. Growth hormone therapy is used for short stature, not sleep disturbances. C. Williams syndrome; dietary restriction of calcium and vitamin D: While Williams syndrome is associated with hypercalcemia, it does not present with self-injurious behavior or the described facial features. D. Down syndrome; behavioral therapy: Down syndrome has characteristic facial features (flat nasal bridge, upslanting palpebral fissures) but does not present with an inverted melatonin rhythm or self-hugging behaviors. E. Angelman syndrome; benzodiazepines for sleep: Angelman syndrome is characterized by severe intellectual disability, a happy demeanor, and ataxia. Sleep disturbances in Angelman syndrome are typically managed with behavioral strategies or melatonin, not benzodiazepines.
What is the genetic cause of Smith-Magenis Syndrome (SMS)?
Smith-Magenis Syndrome is caused by a micro-deletion on chromosome 17p11.2 or mutations in the RAI1 gene.
What are the characteristic facial features of Smith-Magenis Syndrome?
Facial features include a broad, square-shaped face, deep-set eyes, a flat midface, and a prominent forehead and jaw.
What are the hallmark behavioral characteristics of Smith-Magenis Syndrome?
Patients often exhibit self-injurious behaviors, hand-biting, head banging, temper tantrums, stereotypic movements (e.g., hand licking, page flipping), and sleep disturbances due to an inverted melatonin rhythm.
These patients are also known to place toys in their orifices.
What are the cardiovascular findings sometimes associated with Smith-Magenis Syndrome?
Some patients may have congenital heart defects, such as ventricular septal defects (VSDs) or tetralogy of Fallot.
What are the common developmental and intellectual outcomes in Smith-Magenis Syndrome?
Patients typically have mild to moderate intellectual disability and global developmental delays, particularly in speech and language.
What sleep disturbances are seen in Smith-Magenis Syndrome?
Patients commonly experience difficulty falling asleep, frequent awakenings, and daytime sleepiness due to an abnormal circadian melatonin secretion pattern.
What are the musculoskeletal findings associated with Smith-Magenis Syndrome?
Findings include short stature, scoliosis, and brachydactyly (short fingers and toes).
Brachycephaly (bray-key-kef-a-lee) is where the back of a baby’s head is flat. Like plagiocephaly, brachycephaly does not affect brain growth. However, it may change a baby’s physical appearance.
How is Smith-Magenis Syndrome diagnosed?
Diagnosis is confirmed with genetic testing, including microarray analysis or sequencing of the RAI1 gene, to detect deletions or mutations.
What is the management strategy for Smith-Magenis Syndrome?
Management includes behavioral therapy, speech and occupational therapy, melatonin supplementation for sleep disturbances, and treatment of associated medical issues.
What is the prognosis for patients with Smith-Magenis Syndrome?
With supportive care and intervention, patients can achieve improved quality of life, but they often face lifelong developmental and behavioral challenges.
