A 13-month-old girl is brought to the office by her mother. She is worried that there is something wrong and explains, "My daughter used to sit on her own and loved babbling and clapping her hands. She still plays with her sisters and likes snuggles, but for the past 3 months she hasn't babbled as much, and can no longer sit without my help. She twists her hands together and I cannot get her to stop. I am worried that the skin on her hands is getting red, dry, and painful." Weight and height are in the 60th percentile. The patient's head growth, however, has decreased from the 50th to the 40th percentile in 3 months. On examination, the child is globally hypotonic and unable to sit upright without being held. She makes no sound apart from an occasional grunt. She shows interest in toys the doctor provides her but does not reach out for them, wringing her hands repeatedly. Which of the following best explains this patient's condition?

Question

A 13-month-old girl is brought to the office by her mother.  She is worried that there is something wrong and explains, "My daughter used to sit on her own and loved babbling and clapping her hands.  She still plays with her sisters and likes snuggles, but for the past 3 months she hasn't babbled as much, and can no longer sit without my help.  She twists her hands together and I cannot get her to stop.  I am worried that the skin on her hands is getting red, dry, and painful."  Weight and height are in the 60th percentile.  The patient's head growth, however, has decreased from the 50th to the 40th percentile in 3 months.  On examination, the child is globally hypotonic and unable to sit upright without being held.  She makes no sound apart from an occasional grunt.  She shows interest in toys the doctor provides her but does not reach out for them, wringing her hands repeatedly.  Which of the following best explains this patient's condition?

Quizplus · Accepted Answer

This patient's normal development through age 10 months followed by regression (eg, loss of babbling and motor control) and development of hand wringing is characteristic of Rett syndrome, a neurodevelopmental disorder that occurs mainly in girls. Most cases are due to de novo mutations in the X-linked MECP2 gene. Rett syndrome is characterized by normal development until age 6-18 months, followed by a loss of motor and language skills and the development of stereotypic hand movements. Deceleration of head growth is a classic feature of Rett syndrome and can be an early sign. Other features include seizures, intellectual disability, autistic features, and breathing abnormalities. There is no specific therapy for Rett syndrome; many patients survive well into adulthood with severe, permanent neurologic deficits. (Choice A) Features of Angelman syndrome include a happy disposition, jerky gait, and hand flapping. Development is commonly delayed rather than initially normal. (Choice B) Although this patient has deficits in verbal communication and stereotypical hand movements, she does not display other features of autism spectrum disorder (ASD) such as deficits in social reciprocity, emotional restriction, or repetitive interests. She plays and snuggles with family and appears to be trying to interact with the doctor. (Choice C) Fragile X syndrome mainly affects males and is associated with CGG trinucleotide repeats on the X chromosome. Features include intellectual disability; a long, narrow face; large protruding ears; macrocephaly; and macroorchidism. (Choice D) Lesch-Nyhan syndrome is an X-linked recessive disorder characterized by a deficiency in HGPRT (hypoxanthine guanine phosphoribosyltransferase), leading to an increase in uric acid levels. Although hypotonia and involuntary movements such as hand wringing may be present, developmental milestones are typically delayed rather than normal. Gout and self-mutilating behaviors (eg, lip and finger biting) are commonly seen. (Choice F) Tay-Sachs disease is a lysosomal storage disease caused by a deficiency in beta-hexosaminidase A (Hex A). Like Rett syndrome, it presents with a regression of motor skills, but it typically begins earlier (age 2-6 months) and is associated with macrocephaly and a cherry red spot on the macula. Educational objective: Rett syndrome is characterized by loss of speech and motor skills, deceleration of head growth, and stereotypic purposeless hand movements after a period of normal development. It affects mainly girls and is associated with mutations in the MECP2 gene. __________ References: Is it possible to diagnose Rett syndrome before classical symptoms become obvious? Review of 24 Danish cases born between 2003 and 2012. (http://www.ncbi.nlm.nih.gov/pubmed/26228846) Rett syndrome: disruption of epigenetic control of postnatal neurological functions. (http://www.ncbi.nlm.nih.gov/pubmed/26060191)

A 13-Month-Old Girl Is Brought to the Office by Her