Thread by @studyrare

Do you have an undiagnosed patient despite exome sequencing? 🤔

It could be a repeat expansion disorder.

Here are 5 scenarios that should make you think of a repeat expansion disorder in adults. 🧵

#GeneChat #MedTwitter

1/5
A 21 y man with slurred speech who is experiencing difficulty with coordination and balance over the last several years. He fatigues easily.

Diagnosis: Friedreich's ataxia
Genetics: GAA repeat expansion in the 1st intron of FXN
Inheritance: Autosomal recessive

#Neurology

2/5
A 25 y woman with hot flashes and irregular menses over the last several months (early menopause).

Diagnosis: Fragile X-associated primary ovarian insufficiency (FXPOI)
Genetics: CGG repeat expansion in the 5' UTR of FMR1
Inheritance: X-linked

#OBGYN

3/5
A 50 y man with “food getting stuck in his throat,” worse over the past several years. He has droopy eyelids.

Diagnosis: Oculopharyngeal muscular dystrophy
Genetics: Polyalanine repeat expansion in PABPN1
Inheritance: Autosomal dominant

#GITwitter

4/5
A 30 y woman with a history of cataracts, difficulty letting go after a handshake, and muscle weakness.

Diagnosis: Myotonic dystrophy type 1
Genetics: CTG repeat expansion in the 3’UTR of DMPK
Inheritance: Autosomal dominant

#Neurology #Ophthalmology

5/5
A 38 y woman has a lifelong history of snoring and nocturnal gasping. A sleep study shows multiple central apneas.

Diagnosis: Congenital hypoventilation syndrome
Genetics: Polyalanine repeat expansion in PHOX2B
Inheritance: Autosomal dominant

#Pulmonary

Remember, repeat expansion disorders are not routinely detected on exome & require separate testing.

If the diagnostic workup has not yielded answers thus far AND a patient presents similar to any of these scenarios, consider testing for a repeat expansion disorder.