Miscellaneous genetic disorders: Pathology review

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Miscellaneous genetic disorders: Pathology review




Miscellaneous genetic disorders: Pathology review

USMLE® Step 1 questions

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USMLE® Step 1 style questions USMLE

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A 2-year-old boy is brought to the pediatrician by his parent for a routine checkup. His parent describes him as very friendly, even with strangers. The patient’s growth was slow in the first year of life, where he was placed in the 3rd percentile for weight. His weight improved with a special formula, and he is currently at the 10th percentile for weight. The child was also discovered to have supravalvular aortic stenosis at two months. Physical examination demonstrates a child with a broad nasal bridge, wide forehead, and upturned nose. The child is extremely friendly with the physician. Labs demonstrate hypercalcemia. Which of the following is most likely the disease mechanism in this patient?  


At the clinic, 30 year old Linda comes with her 2 year old toddler for a yearly pediatric checkup. Linda tells the pediatrician that, while she was bathing her son, she noticed that his testes are unusually large. Clinical examination confirms enlarged testes, and additionally, the pediatrician noticed dysmorphic facial features including a long, narrow face; prominent forehead and jaw; and large, protruding ears. Later that day, 27 year old Samantha comes to the clinic with her 5 year old son because she noticed that he often has strange episodes of laughter and smiling. In addition, she mentions that he had experienced seizures several months ago.

Based on the clinical findings, the pediatrician concludes that both children have some form of genetic disorder, and orders genetic testing to confirm the diagnosis. Now, let’s go over genetic disorders such as fragile X syndrome, imprinting disorders, Cri-du-chat syndrome, and Williams syndrome.

First, let’s start with fragile X syndrome. This is an X-linked disorder caused by inactivation of the FMR1 gene, which is located on the long arm of the X chromosome. These individuals have over 200 CGG trinucleotide repeats on the FMR1 gene, which leads to its hypermethylation and subsequent inactivation. Fragile X syndrome is the most common cause of inherited intellectual disability, and the second most common cause of genetically associated psychiatric disorders, after Down syndrome. Individuals with fragile X syndrome can have delayed speech and motor development. In addition, individuals may have anxiety disorders, autism, and attention deficit-hyperactivity disorder; as well as mitral valve prolapse. For your exam, it’s important to know the key physical findings of fragile X syndrome includes enlarged testes, also known as macroorchidism; and dysmorphic facial features, like a long narrow face, with large protruding ears, and prominent forehead and jaw. The treatment of fragile X syndrome includes speech, occupational, and physical therapy. Clinicians should also focus on the prevention of common medical problems associated with the disorder such as gastroesophageal reflux, sinusitis, and otitis media.


  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Public Health Literature Review of Fragile X Syndrome" Pediatrics (2017)
  4. "‘Puppet’ Children A Report on Three Cases" Developmental Medicine & Child Neurology (2008)
  5. "Preventive Management of Children with Congenital Anomalies and Syndromes" Cambridge University Press (2000)
  6. "Cri du Chat syndrome" Orphanet Journal of Rare Diseases (2006)

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