An 18-month-old girl is brought to the emergency department after having a seizure in day care. The staff reports that "she suddenly fell down and started shaking," but they also note that the patient has seemed quieter and has repeatedly pulled at her hair over the past month. The patient's mother says, "My daughter used to say 'mama' and 'papa' and babble away but has begun to talk less in the past few months. She's also become more needy, wanting me to feed her rather than using a spoon herself." Medical history is significant for 3 ear infections in the past year and another seizure thought to have been febrile in origin. Family history is significant for early-onset Alzheimer disease in the patient's paternal grandfather and retinoblastoma in a paternal cousin. The patient is afebrile, and other vital signs are normal. On physical examination, the patient makes eye contact with the physician but speaks no words. She is noted to have a lurching gait. Which of the following would most likely establish a diagnosis in this patient?

Question

An 18-month-old girl is brought to the emergency department after having a seizure in day care.  The staff reports that "she suddenly fell down and started shaking," but they also note that the patient has seemed quieter and has repeatedly pulled at her hair over the past month.  The patient's mother says, "My daughter used to say 'mama' and 'papa' and babble away but has begun to talk less in the past few months.  She's also become more needy, wanting me to feed her rather than using a spoon herself."  Medical history is significant for 3 ear infections in the past year and another seizure thought to have been febrile in origin.  Family history is significant for early-onset Alzheimer disease in the patient's paternal grandfather and retinoblastoma in a paternal cousin.  The patient is afebrile, and other vital signs are normal.  On physical examination, the patient makes eye contact with the physician but speaks no words.  She is noted to have a lurching gait.  Which of the following would most likely establish a diagnosis in this patient?

Quizplus · Accepted Answer

11ec25c8_d585_1c37_bc81_e3717a34fa60_MD0003_00 This patient's speech regression, loss of purposeful hand movements, gait disturbance, and seizures are key features of Rett syndrome (RS). RS is an X-linked genetic disorder that occurs mainly in girls and is characterized by neurodevelopmental regression at age 6-18 months after a period of normal development. In addition to loss of purposeful hand movements (eg, inability to feed herself, stereotypical movements such as hair-pulling) and gait disturbances (eg, lurching gait), other findings can include seizures, which occur in the majority of patients (like this girl), as well as breathing abnormalities (eg, hyperventilation, hypoventilation) and autistic behaviors. Deceleration of head growth is also an early sign of disease. Evaluation of any child with neurodevelopmental regression should include a DNA analysis to identify pathogenic mutations. A diagnosis of RS is confirmed if an MECP2 gene mutation is detected in a patient with characteristic clinical features. Further genetic testing may be required to identify rare mutations in other genes if MECP2 analysis is negative. (Choice B) Enzyme analysis (eg, hexosaminidase A, sphingomyelinase) is performed for a suspected lysosomal storage disease such as Tay-Sachs or Niemann-Pick, which can cause neurodevelopmental regression, particularly of motor skills. However, presentation is typically before age 6 months, and repetitive hand movements (ie, hair-pulling) would not be expected. (Choice C) Although MRI of the head is frequently part of the workup for neurodevelopmental disorders and seizures, imaging would not establish the diagnosis of RS because findings are generally nonspecific (eg, cerebral hypoplasia). (Choice D) A friable, white retinal mass on ophthalmologic evaluation can confirm the diagnosis of retinoblastoma. Although a positive family history increases the risk, retinoblastoma causes leukocoria, strabismus, and nystagmus. These signs are not seen in this patient, whose neurologic deterioration is consistent with RS, a condition not associated with ophthalmologic abnormalities. (Choice E) Serum amino acids and urine organic acids are used to evaluate for amino acid disorders such as phenylketonuria and maple syrup urine disease. Although developmental delay is common with these disorders, a period of normal development followed by regression does not occur. Educational objective: Rett syndrome occurs mainly in girls and is characterized by neurodevelopmental regression (ie, loss of speech and purposeful hand movements, gait disturbance) after a period of normal development. Seizures are also common, and a MECP2 mutation on DNA analysis confirms the diagnosis. References: MeCP2 mutations: progress towards understanding and treating Rett syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/28212680) Epilepsy in Rett syndrome-lessons from the Rett networked database. (http://www.ncbi.nlm.nih.gov/pubmed/25789914) Genetic landscape of Rett syndrome spectrum: improvements and challenges. (http://www.ncbi.nlm.nih.gov/pubmed/31409060)

An 18-Month-Old Girl Is Brought to the Emergency Department After