Congenital Musculoskeletal

Disorders

S. Yudha Patria
Pediatrics Dept. Fac. Medicine, Gadjah
Mada Univ, Yogyakarta

Syndactyly

Limited Movement
may due to...

Pain
Decrease ROM
Unstable Bone
Muscles weakness

Congenital Weakness

Could be problems in:

- CNS
- Nerves
- Myo-neural junction
- Muscles
- Bones

Genetics defect of genetic materials major

cause of congenital anomalies

Congenital bone defects:

- Achondroplasia
- Osteogenesis imperfecta

Congenital Muscle(s) weakness

- Myopathies
- Muscular dystrophies
- Spinal muscle atrophy

Achondroplasia

Yudha Patria, MD & PhD

= Chondrodysplasia

Transmitted: autosomal dominant with

complete penetrance

De novo mutations cause 75-80% of

cases

Incidence: 1 in 15,000 to 1 in 40,000

live births

Occurs in all races and in both sexes

same frequency

Etiology

Mutations FGFR3 gene

(fibroblast growth factor receptor-3
gene)

The gene mapped to 4p16.3

99% G1138A or G1138C mutations

G380R amino acid changed

Pathophysiology

The protein (FGFR-3) responds to

signals from growth factors (FGF)
stimulate cell growth and maturation

Mutated FGFR-3 decreased of:

- endochondral ossification
- proliferation of chondrocytes in growth
plate cartilage,
- cellular hypertrophy
- cartilage matrix production

The clinical features

Short stature unproportionate type

(average final height: male 131 cm; female 124
cm)

Rhizomelic (proximal): short arms and legs

Limitation of elbow extension
Trident configuration of the hands
Genu varum (bow legs)
Thoracolumbar gibbus in infancy
Exaggerated lumbar lordosis, which develops
when walking begins
Large head with frontal bossing
Normal trunk length

The radiograph of
achondroplasia

Narrowing of the interpediculate

distance of the caudal spine
Notch-like sacroiliac groove
Circumflex on the metaphysis

Head USG or brain CT-scan

enlargement of
ventricles
others abnormalities

- Genetic analysis:
Pedegree analysis
Gene mutation analysis

Management

The follow-up care

( international symposium on achondroplasia):
Growth and head circumference measurements plotted
on growth curves standardized for achondroplasia
Neurologic examinations (CT scan, MRI,
somatosensory-evoked potentials, and
polysomnography )
Management of frequent middle ear infections and
dental crowding

Genetic counseling

Height for children with

achondroplasia

Differential Diagnosis:
- Hypochondroplasia (milder form)
- FGFR related Craniostosis
Crouzon Syndrome
- Thanatophoric dysplasia
- Severe achondroplasia with
developmental delay and
acanthosis

Crouzon Syndrome

Thanatophoric Dysplasia

Osteogenesis Imperfecta
(OI)

Definition

Osteogenesis imperfecta (OI)

is a group of genetic diseases of collagen
in which the bones are formed
improperly, making them fragile and
prone to breaking

Collagen is a fibrous protein material,

serves as the structural foundation of
skin, bone, cartilage, and ligaments

OI

OI results from abnormalities

in the collagen gene COL1A1 or COL1A2

In OI type I, II, and III, the gene map locus is

17q21.31-q22, 7q22.1; and
type IV map locus is 17q21.31-q22 only

Demographics
Affects equal numbers of males and females,
and occurs in about one of every 20,000
births.
The pattern of inheritance is autosomal
dominant

Signs and symptoms

Type I (the most common and mildest type)

Bones are predisposed to fracture, with most

fractures occurring before puberty. People with OI
type I typically have about 2040 fractures before
puberty
Stature is normal or near-normal
Joints are loose and muscle tone is low
Sclera have blue, purple, or gray tint
Face shape is triangular
Tendency toward scoliosis
Bone deformity is absent or minimal
Dentinogenesis imperfecta may occur, causing
brittle teeth

Type II

Type II is the most severe form of OI

(lethal form)
Lethal at or shortly after birth, often as a
result of respiratory problems
Fractures are numerous and bone
deformity is severe
Stature is small with underdeveloped
lungs.
Collagen is formed improperly.

Type III

Bones fracture easily (often present at birth), and

x rays may reveal healed fractures that occurred
before birth. People with OI Type III may have
more than 100 fractures before puberty

Stature is significantly shorter than normal

Joints are loose and muscle development is poor in

arms and legs
Rib cage is barrel-shaped.
Respiratory problems are possible
Bones are deformed (often severe)
Hearing loss is possible.
Others, similar to type 1

Type IV

Symptom falls between Type I and Type III

in severity

Bones fracture easily, with most fractures

occurring before puberty
Stature is shorter than average.
Sclera (whites of the eyes) are normal in
color, appearing white or near-white.
Bone deformity is mild to moderate,
scoliosis is likely
Rib cage is barrel-shaped

Diagnosis

Diagnosis OI often possible solely on clinical

features and x ray findings

Diagnosis is suspected when a baby has bone

fractures after having suffered no apparent injury

Another indication is small, irregular, isolated

bones in the sutures between the bones of the
skull (wormian bones)

Collagen or DNA tests may help confirm a

diagnosis of OI. These tests generally require
several weeks

Congenital Muscular
Disorders
S. Yudha Patria
Dept. Pediatrics

Congenital muscular disorders

consist of heterogeneous group
muscular diseases genetic
abnormality

The major clinical features:

- muscle weakness
- hyporeflexia
- hypotonia
- dysmorphic features

Onset infancy and early childhood

Non-progressive,
Slow progressive with age
Definitive diagnosis
Histopathologic in
the muscle
biopsy
Treatment : supportive, gene therapy

Congenital Muscular
Disorders

Myopathies
Muscular dystrophy
Channelopathies

from A Kornberg MD

1. Muscular dystrophy

A group of inherited, progressive muscle

disorders, distinguished clinically by the
selective distribution of weakness

Include:
- Dystrophinopaties (Duchenne & Becker type)
- Limbgirdle muscular dystrophy
- Facioscapulohumeral muscular dystrophy
(Landouzy-Dejerine)

Gower
Maneuver

Pseudohypertrop
hy

Diagnostic Tests

Blood CK

EMG myopathy

Muscle biopsy specific (immuno)

staining

Genetics tests: Duchenne, Becker, Distal-,

some forms of Limb-girdle and EmeryDreifuss dystrophies

Diagnosis

Characteristic clinical findings

age of onset
family history
Serum CK elevated (up to 50 to 100 times )
supported by electromyography
Difinitive: immunostaining of muscle
biopsy
Molecular study

Muscle biopsy. A group of necrotic and regenerating

muscle fibers is apparent

Treatment

No specific treatment exists

Supportive therapy
Gene therapy

2. Channelopathies

Neuromuscular disorders
disturbance of the membrane
conduction system, resulting from
mutations affecting ion channels.
Includes:
- Myotonic Disorders
- Familial periodic paralysis

2.1 MYOTONIC
DISORDERS

A group of disorders characterized by

abnormally slow relaxation after
voluntary muscle contraction due to a
muscle membrane abnormality

Includes:
- Myotonic dystrophy (Steinert's disease)
- Myotonia congenita (Thomsens disease)

2.2 FAMILIAL PERIODIC

PARALYSIS
A group of rare autosomal dominant
disorders characterized by episodes
of flaccid paralysis with loss of deep
tendon reflexes and failure of muscle
to respond to electrical stimulation
Includes:
- Hypokalemic form
- Normokalemic form
- Hyperkalemic form