A 24-month-old girl is brought to the office by her mother due to concerns about walking. The mother says, "She seems so unsteady when she walks. She was walking so well until a few weeks ago, and now she keeps tripping over things." On examination, the patient is sitting on the floor and clapping her hands. She does not answer questions and instead makes babbling sounds. When her mother encourages her to walk, the patient pulls to stand using a chair and has an unsteady gait. The remainder of the examination is normal apart from abrasions on both knees, which her mother explains are from frequent falls. Height and weight track at the 50th percentile. At a checkup 6 months ago, the patient had been saying 1- or 2-word phrases and walking without aid. Which of the following neuropathic changes most likely underlies this patient's presentation?

Question

A 24-month-old girl is brought to the office by her mother due to concerns about walking.  The mother says, "She seems so unsteady when she walks.  She was walking so well until a few weeks ago, and now she keeps tripping over things."  On examination, the patient is sitting on the floor and clapping her hands.  She does not answer questions and instead makes babbling sounds.  When her mother encourages her to walk, the patient pulls to stand using a chair and has an unsteady gait.  The remainder of the examination is normal apart from abrasions on both knees, which her mother explains are from frequent falls.  Height and weight track at the 50th percentile.  At a checkup 6 months ago, the patient had been saying 1- or 2-word phrases and walking without aid.  Which of the following neuropathic changes most likely underlies this patient's presentation?

Quizplus · Accepted Answer

11ec160b_3642_03b7_9249_9d3213d75248_MD0001_00 This child who was previously meeting developmental milestones now has dramatic regression of speech and motor milestones accompanied by repetitive hand movements, which is concerning for Rett syndrome (RS). RS is a sporadic, X-linked genetic disorder characterized by normal development until age 6-18 months, when regression of speech, loss of purposeful hand movements, development of stereotypical movements (eg, clapping), and gait abnormalities occur. MECP2 is a gene encoded on the X chromosome that has abundant expression in the brain. It is thought to impact synaptic maturation and cortical maintenance. Neuropathology is consistent with arrested brain development (eg, impaired dendritic maturation, reduced neuromelanin in substantia nigra) rather than death of neurons (ie, neurodegeneration). Brain growth decelerates after birth, with no further growth after age 4. (Choice A) The accumulation of hyperphosphorylated tau protein, seen in Alzheimer disease, is neurotoxic and can lead to neuronal cell death. However, neuropathology in RS is characterized by arrested development rather than neuronal degeneration. (Choice C) Copper deposition in the lenticular nucleus is characteristic of Wilson disease. Although Wilson disease can present with neuropsychiatric symptoms, including dysarthria and ataxia, it typically presents in adolescence with liver disease; Kayser-Fleischer rings are nearly always present by the time neurologic symptoms develop. (Choice D) Cortical hyperexpansion seems to underly the brain enlargement associated with autism spectrum disorder (ASD). Although ASD can present in toddlers with regression of speech and stereotypical movements (eg, flapping, clapping), it does not usually cause regression of gross motor milestones (eg, walking). (Choice E) Hypoxic ischemic injury during delivery can lead to neonatal encephalopathy, a condition which can result in decreased level of consciousness, seizures, and impaired respiration. However, it would present as neurologic abnormalities shortly after birth, rather than as a regression in milestones after previous normal development. Educational objective: Rett syndrome is a genetic disorder characterized by normal development until age 6-18 months, when regression of speech, loss of purposeful hand movements, development of stereotypical movements, and gait abnormalities occur. Neuropathology shows arrested brain development rather than neurodegeneration. __________ References: Metabolic fingerprints of altered brain growth, osmoregulation and neurotransmission in a Rett syndrome model. (http://www.ncbi.nlm.nih.gov/pubmed/17237885)

A 24-Month-Old Girl Is Brought to the Office by Her