Transcript A CASE OF THE DANCER WHO CAN NO LONGER DANCE

A CASE OF THE DANCER WHO CAN
NO LONGER DANCE
Cecile L. Phan, M.D., F.R.C.P.C.
Yadollah Harati, M.D., F.A.C.P.
Clinical history
• 72 year old dance instructor:
– 2 years history of slowly progressive numbness
started out in the feet and now the legs feel “lead
like”.
– Losing muscle mass in legs and feet.
– Feet flapping on the ground
– Significant balance problem with frequent falls.
– Recently hands became numb and tingling, right
hand weak leading to dropping things.
Clinical history
• Underwent cervical laminectomy and
decompressive surgery without any benefit.
• Had high arch feet for years. Recently noticed
hammer toes.
• Cramps in hands and feet.
• Still able to teach dancing but with great
difficulty.
Clinical history
• Past MHx and SHx
– Hypertension
– Psoriasis
• Allergies:
– NKDA
• Meds:
– Propanolol, HCTZ
• Social Hx
– Non-contributory
Clinical history
• Family history:
– Twin brother has similar symptoms:
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High arched feet, hammer toes
Numbness up to ankles bilaterally
Burning pain in toes
Balance worsening, fallen couple of times
Clinical examination
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General exam normal
Cranial nerves normal
High arched feet, hammer toes
Distal (anterior compartment) > proximal weakness in the
legs
• Absent reflexes in the legs but generally preserved in the
arms
• Dense loss of vibratory and proprioceptive sense past the
knees and mildly reduced vibratory sense at the DIP’s
• Marked sensory ataxia with pseudoathetosis of the feet >
hands
Investigations
• EMG/NCS (outside)
– Moderately severe, mixed axonal and
demyelinating, sensorimotor polyneuropathy
affecting legs > arms
• vitamin B12, vitamin E, thyroid function, SPEP
with immunofixation, anti MAG antibody,
HbA1C, rheumatologic profile, RPR were
normal or negative.
• CSF protein 61 mg/dL
Sural nerve biopsy
Semi-thin sections
Teased fibers: 40% of fibers showed changes of
demyelinating/remyelinating
Treatment
• Trial of IV solumedrol – no benefit
• CMT genetic testing
Genetic testing
• CMT panel:
– Periaxin variant: G>C, nucleotide position 134,
Codon position 45, arginine>proline
– HSPB1 variant: G>A, nucleotide position 9, codon
position 3, no amino acid change
Both mutations were considered to be “variants of
unknown clinical significance”.
Genetic testing
• Twin brother:
– Identical periaxin mutation
– No mutation detected in HSPB1
Periaxin and CMT
• Periaxin:
– structural protein mainly expressed by myelinating
Schwann cells
– interacts with dystroglycan complex and linking
basal lamina to the Schwann cell cytoskeleton
– Contributing to proper compartmentalization and
elongation of Schwann cells, and maintenance of
myelin sheath
Periaxin and CMT
Periaxin CMT
Clinical features Autosomal Recessive
Early onset
Our patient
Autosomal Dominant
Late onset
Demyelinating neuropathies
(CMT4F) and Déjèrine-Sottas .
Demyelinating (NBx)
Axonal (EMG)
Slow progression (decades)
Slow progression (years)
Prominent sensory involvement
with sensory ataxia.
Weakness limited to distal limb
muscles.
Scoliosis common
No scoliosis
Periaxin CMT
Our patient
EMG/NCS
NCS severely slowed CV
SNAP’s usually undetectable
CV – 34-38 m/s in legs, normal
in arms.
SNAP – absent surals
Nerve biopsy
Moderate-severe demyelinating No onion bulbs
neuropathy
Loss of axons
Onion bulbs
Focally fold myelin or tomacula
Back to our case
• Phenotype, EMG/NCS and biopsy features are not
consistent with CMT 4F
• Is the periaxin mutation truly a “variant of unknown
clinical significance”? Or..
• Pathogenic for a novel variant of Autosomal
Dominant, axonal CMT.