MEDizzy - A 2-year-old boy is being evaluated for short stature and

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General Pathology (I)

A 2-year-old boy is being evaluated for short stature and failure to thrive. Physical examination finds the boy to be short with thin skin and alopecia. He has a small face and jaw with a pinched nose. The skin of his face is wrinkled and his lips appear atrophic. What is the most likely cause of this child’s abnormality?

ExplanationProgeria (or Hutchinson-Gilford syndrome) is caused by a mutation in the LMNA gene on chromosome 1, which normally codes for lamin A. The mutant gene codes for a defective protein called progerin, which disrupts the normal structure of the nucleus and of heterochromatin. Progeria is characterized by symptoms of premature aging, which initially include failure to grow and alopecia. Later patients develop stiffness of joints, atherosclerosis, and cardiovascular problems. Individuals with progeria have a characteristic facial appearance—small face and jaw with a pinched nose. Werner syndrome is a similar appearing disease that first causes symptoms in affected individuals in their late teens. Werner syndrome is typically first identified when an adolescent fails to have a normal growth spurt. Werner syndrome is caused by a mutation in the WS gene, which results in the production of a defective DNA-dependent enzyme, including ATPase, helicase, and exonuclease.