X-linked Dominant Disorders

Question 1

Hypophosphatemic Rickets

Answer 1

-Mutated gene–> PHE, which regulates fibroblast growth factor.

This mutation Inhibits the kidneys ability to reabsorb phosphate into the blood stream and leads to Hypophosphatemia

Other clinical signs:

• Short stature
• Bone deformity

Question 2

Fragile X Syndrome

Answer 2

What is the molcular basis of Fragile X syndrome?

• Gene mutated: FMR1
• Trinucleotide repeat disorder- CGG
• Most common cause of inherited developmental delay
• Anticipation is seen.
• Maternal transmission bias

What are the clinicar signs?

• Intellectual disabilities
• Dysmorphic features: **large ears, long face, macroorchidism
• Autistic behavior
• Social anxiety
• Hand flapping/biting
• Aggression

Question 3

Fragile X Associated Tremor Ataxia

Answer 3

–White matter lesions on MRI
–Intention tremor, Gait ataxia

•FMR1- related primary ovarian Insufficiency
–Cessation of menses before age 40

Question 4

Rett Syndrome

Answer 4

Mutated Gene: MECP2, which is in charge of producing a Methyl CpG binding protein essential for the normal function of nerve cells

What are some clinical manifestations?

•Loss of normal movement and coordination
•Acquired microcephaly
•Loss of communication skills
•Failure to thrive
•Seizures
•Abnormal hand movements**