2025 – PAGE 258 – GENETICS & INHERITED DISEASES

JOHANSON-BLIZZARD SYNDROME

Johanson-Blizzard syndrome is a multisystem congenital disorder. Findings include pancreatic insufficiency, hypoplasia (or aplasia) of the nostrils, and intellectual disability.

MNEMONIC: Imagine having a stuffy/TIGHT NOSE while being caught in a BLIZZARD.

IMAGE: (mnemonic image) Look! Scarlett Johansson is holding her PANCREAS!

www.pbrlinks.com/JOHANSON1

X-LINKED DISORDERS

PEARLS:

• X-linked disordersare RULED OUT if you see male-to-male transmissions!
• A vignette about a male patient that discusses ANYTHING about a MATERNAL UNCLE should alert you to a possible X-linked disorder.
• Most X-linked disorders are X-linked RECESSIVE. The dominant ones seem to select themselves out. These X-linked recessive disorders tend to be enzyme or protein deficiencies; thus, several inborn errors of metabolism are X-linked recessive.

X-LINKED DOMINANT DISORDERS

X-linked dominant disorders are extremely rare.

• PEARL: Because these are dominant disorders, the inheritance pattern will look very similar to an autosomal dominant pattern. A key difference is that the X-linked disorder will be present in 100% of the daughters of an affected MALE and NONE of his sons. This occurs because the affected father only has one X to give to his daughters, and that X is affected. His sons get a Y from him and an unaffected X from their mothers.

FAMILIAL HYPOPHOSPHATEMIC RICKETS

Familial Hypophosphatemic Rickets is also known as VITAMIN D RESISTANT RICKETS.

AICARDI SYNDROME

In Aicardi syndrome, there is a missing corpus callosum and infantile spasms or epilepsy. Patients also have intellectual disability.

(DOUBLE TAKE) ALPORT SYNDROME (AKA ALPORT’S SYNDROME)

Alport syndrome (AKA Alport’s syndrome) is primarily an X-linked dominant disorder. The findings are more severe in males and include RENAL disease (which starts with hematuria and progresses to end-stage renal disease), bilateral sensorineural hearing loss; and eye/vision problems. Females may be noted to have hematuria that can eventually progress to ESRD. To recap, boys have hearing, vision, AND kidney problems. Girls only have renal issues.

MNEMONIC: At Al’s PORT, X marks the spot where the boats have to dock. Consider adding a story about poor AL and the KIDNEY-SHAPED boat he crashed into his PORT because he had POOR VISION and POOR HEARING. It was so bad that he couldn’t see or hear everyone on the dock yelling at him to slow down!