A 6-year-old boy is brought to the office by his mother due to learning difficulties at school. The patient was adopted from an overseas orphanage at age 5 and stayed home until beginning kindergarten 6 months ago. His birth and developmental history are unknown. Since beginning school, he has struggled to keep up with reading and writing. Educational testing was completed and showed an intelligence quotient (IQ) of 68. Audiology revealed a mild conductive hearing loss in his right ear. The patient's mother says, "He is a really happy kid and enjoys playing with his older siblings. I know he doesn't talk as much as other kids his age, but I thought that would improve with time." Vital signs are within normal limits; weight and height curves are at the 70th and 10th percentiles, respectively. The patient is sitting on the floor playing with a range of toys. Physical examination is significant for a flat nasal bridge and a grade 3 holosystolic murmur at the lower left sternal border. He makes eye contact, has a friendly demeanor, and responds to questions with 3- to 4-word phrases. Which of the following tests is most likely to reveal the diagnosis?

Question

A 6-year-old boy is brought to the office by his mother due to learning difficulties at school.  The patient was adopted from an overseas orphanage at age 5 and stayed home until beginning kindergarten 6 months ago.  His birth and developmental history are unknown.  Since beginning school, he has struggled to keep up with reading and writing.  Educational testing was completed and showed an intelligence quotient (IQ) of 68.  Audiology revealed a mild conductive hearing loss in his right ear.  The patient's mother says, "He is a really happy kid and enjoys playing with his older siblings.  I know he doesn't talk as much as other kids his age, but I thought that would improve with time."  Vital signs are within normal limits; weight and height curves are at the 70th and 10th percentiles, respectively.  The patient is sitting on the floor playing with a range of toys.  Physical examination is significant for a flat nasal bridge and a grade 3 holosystolic murmur at the lower left sternal border.  He makes eye contact, has a friendly demeanor, and responds to questions with 3- to 4-word phrases.  Which of the following tests is most likely to reveal the diagnosis?

Quizplus · Accepted Answer

11ec25c8_d7c7_43a1_bc81_d3db5afb0b6e_MD0003_00 This patient with learning difficulties and a low intelligence quotient (IQ) has intellectual disability. In the setting of dysmorphic features or a family history of intellectual disability, a genetic cause should be suspected. In this case, the most likely cause is Down syndrome, the most common chromosomal abnormality associated with intellectual disability. Congenital heart defects (eg, atrioventricular defect, ventricular septal defect [VSD]) occur in 50% of patients; the holosystolic murmur in this case is consistent with a VSD. Hearing impairment due to congenital hearing loss or frequent otitis media is also common. Patients often have a friendly demeanor and poor vertical growth, as seen here. The diagnosis is frequently established based on prenatal testing or characteristic dysmorphic features at birth (eg, flat nasal bridge). However, in a patient with mosaicism (extra copy of chromosome 21 in some cells), such dysmorphic features may be less prominent and diagnosis may be delayed. A karyotype should be performed; identification of trisomy 21 is diagnostic. dysmorphic features at birth (Choice A) FMR1 DNA analysis detects the gene mutation responsible for Fragile X syndrome (FXS). Boys with FXS typically have tall stature and a long, narrow face, not a flat nasal bridge. FXS also would not explain this patient's hearing loss or murmur. FXS (Choice C) Rett syndrome, typically due to MECP2 mutations, is a neurodevelopmental disorder characterized by loss of speech after a period of normal development, as well as stereotypical hand movements and gait abnormalities. It occurs almost exclusively in girls. (Choice D) MRI of the head is indicated for focal neurologic deficits, seizures, or progressive degenerative neurologic symptoms. MRI findings in patients with mild intellectual disability are often normal or nonspecific and would not diagnose DS. (Choice E) Serum hexosaminidase A levels should be measured for suspected Tay-Sachs disease, a lysosomal storage disease that usually presents in infancy with severe neurodegeneration (eg, progressive weakness, loss of motor skills) and death by age 2-5. (Choice F) Phenylketonuria, an autosomal recessive disorder caused by phenylalanine hydroxylase deficiency, causes intellectual disability; however, other characteristic features (eg, musty odor, seizure, hypopigmented skin) also would be expected. In addition, it is not associated with heart disease or hearing loss. Educational objective: Down syndrome should be suspected in a child with intellectual disability and characteristic dysmorphic features, cardiac defects, and hearing loss. Trisomy 21 on karyotype is diagnostic. References: Down syndrome-genetics and cardiogenetics. (http://www.ncbi.nlm.nih.gov/pubmed/29218069) Diagnosis and management of Down syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/24127006)

A 6-Year-Old Boy Is Brought to the Office by His