Pediatric Myopathies

Question 1

Why do we perform developmental screens?

Answer 1

The sooner we identify developmental delays, the sooner we can intervene

[Note: Remember that a failed screen in simply an indication for a more thorough evaluation]

Question 2

Name the 4 general domains of pediatric development

Answer 2

Gross motor

Fine motor

Language

Cognitive/Social-Emotional and Behavioral

Question 3

If developmental delays are identified, early intervention is key. It is important to note that not hitting developmental milestones can be serious, but hitting milestones and then ______ is even more ominous

Answer 3

Regressing

Question 4

Gross motor developmental milestones for 6 months, 9 months, and 1 year screening

Answer 4

6 months — Sits momentarily

9 months — pulls up, cruises, sits well without support

1 year — stands momentarily

Question 5

Gross motor developmental milestones for 2 years and 3 years screening

Answer 5

2 years — walks up stairs, kicks ball forward

3 years — tricycle

Question 6

Gross motor developmental milestones for 4 years and 6 years screening

Answer 6

4 years — balance on one foot (1-3 seconds), hop on one foot

6 years — skips

Question 7

At which of the following ages should a child be able to skip?

A. 6 months
B. 9 months
C. 1 year
D. 2 years
E. 3 years 
F. 4 years
G. 6 years

Answer 7

G. 6 years

Question 8

At which of the following ages should a child be able to walk up stairs and kick a ball forward?

A. 6 months
B. 9 months
C. 1 year
D. 2 years
E. 3 years 
F. 4 years
G. 6 years

Answer 8

D. 2 years

Question 9

At which of the following ages should a child be able to pull themselves up, cruise around, and sit well without support?

A. 6 months
B. 9 months
C. 1 year
D. 2 years
E. 3 years 
F. 4 years
G. 6 years

Answer 9

B. 9 months

Question 10

At which of the following ages should a child be able to stand momentarily?

A. 6 months
B. 9 months
C. 1 year
D. 2 years
E. 3 years 
F. 4 years
G. 6 years

Answer 10

C. 1 year

Question 11

At which of the following ages should a child be able to balance on one foot for 1-3 seconds and hop on one foot?

A. 6 months
B. 9 months
C. 1 year
D. 2 years
E. 3 years 
F. 4 years
G. 6 years

Answer 11

F. 4 years

Question 12

At which of the following ages should a child be able to sit momentarily?

A. 6 months
B. 9 months
C. 1 year
D. 2 years
E. 3 years 
F. 4 years
G. 6 years

Answer 12

A. 6 months

Question 13

At which of the following ages should a child be able to ride a tricycle?

A. 6 months
B. 9 months
C. 1 year
D. 2 years
E. 3 years 
F. 4 years
G. 6 years

Answer 13

E. 3 years

Question 14

Thorough, standardized, and validated developmental screening tool often performed at 9, 18, and 24 or 30 months of age

Answer 14

DDST-II (Denver Developmental Screening Test II)

Question 15

_____ = Muscle disease unrelated to any disorder of innervation or neuromuscular junction

Answer 15

Myopathy

Question 16

Inheritance of DMD

Answer 16

X-linked recessive

[Carrier mom, sons have a 50% chance of having DMD, daughters have 50% chance of being carriers]

Note that 33% of cases are due to spontaneous mutations

Frameshift mutations disrupt reading frame —> absence of muscle dystrophin —> severe muscle weakness

Question 17

If mom is a carrier of DMD, and has a daughter that is a carrier, what are some clinical features that may appear in the daughter?

Answer 17

May have CK elevation

May develop cardiomyopathy, muscle weakness, or muscle cramps

Question 18

Clinical features of DMD

Answer 18

Weak neck flexors

Delayed walking, difficulty running, can’t “keep up”

Broad-based, waddling, lordotic gait

Gowers sign (due to proximal mm. weakness)

Calf and thigh muscle hypertrophy (early on)

Toe-walking by age 6

Limited hip flexion due to IT band contractures

Progressive scoliosis, loss of independent ambulation by age 9-10

Compromised respiratory status

Cardiomyopathy

Gastric hypomotility

Intellectual impairment in some — ADD, learning disability

Question 19

What is Gowers sign?

Answer 19

Sequence of postures used in attaining the upright position in pts with DMD

First legs are pulled up under the body and weight is shifted to hands and feet, hips are then thrust in the air as knees are straightened and hands are brought close to legs, trunk is slowly extended by the hands walking up the thighs until erect position is attained

Question 20

Inheritance and genetics of BMD

Answer 20

X-linked recessive

Caused by in-frame mutation in dystrophin gene —> production of abnormal or semi-functional dystrophin [less severe mm. weakness than DMD]

Question 21

Clinical features of BMD

Answer 21

Proximal mm. weakness after age 5 (older presentation than DMD)

Maintenance of independent walking until after age 16

Preserve anti-gravity strength of neck flexors

Age of death varies between 4th and 6th decades of life

Question 22

Describe presentation of congenital muscular dystrophies

Answer 22

Present at birth or early infancy

Hypotonia
Severe muscle weakness (proximal > distal)
Joint contractures

May present with: malformations of eyes, malformations of brain, cardiomyopathy, and/or rigid spine

Question 23

Role of dystrophin in muscular dystrophies

Answer 23

Dystrophin is required for muscle membrane stability (anchoring) — occurs in skeletal mm., cardiac mm., smooth mm., and brain

Without dystrophin, the membrane tears, and muscle necrosis and fibrosis occurs

Chronic muscle damage outpaces the body’s ability to repair

Question 24

What is the importance of GGT in differentiating between muscle disease and liver disease?

Answer 24

GGT (gamma-glutamyl transferase) level can help determine if the liver is involved

If elevated — think liver

If normal — think muscle

Question 25

Describe statin induced myopathy

Answer 25

Necrotizing and inflammatory myopathy

Symptoms include muscle weakness, pain, and tenderness

Elevation of CK to more than 10x normal

[occurs in 0.5% of pts who use a statin]

Question 26

What is the most common idiopathic inflammatory myopathy in children?

Answer 26

Juvenile dermatomyositis

Question 27

Major clinical findings of juvenile dermatomyositis

Answer 27

Mean age of onset 7 y/o

Generalized muscle weakness (proximal > distal)

Red or purplish heliotrope rash over eyelids

Raised erythematous papules over extensor joint surfaces (Gottren papules)

Thrombi or hemorrhage in peri-ungual capillary beds

Question 28

Glycogen storage disorder type 2 (Pompe disease) is due to autosomal recessive acid alpha-glucosidase gene mutations, resulting in buildup of glycogen in lysosomes of cells, especially muscle.

What are clinical features?

Answer 28

Presents in early infancy

Generalized weakness and hypotonia
Hypertrophic cardiomyopathy
Respiratory failure
Feeding difficulty
Hearing loss

Question 29

Important serum measurement to get in genetic or acquired muscle diseases

Answer 29

Serum creatine kinase

Question 30

Course and prognosis of mitochondrial myopathies

Answer 30

Most often affect multiple organs (can be limited to one organ); organs dependent on aerobic metabolism are most affected — heart, skeletal mm., brain

Present at any age

May be “syndromic” (e.g., mitochondrial encephalomyopathy with lactic acidosis and stroke-like symptoms aka MELAS) or “non-syndromic”

SYMPTOMS AND PROGNOSIS VARY GREATLY