KONGENITAL DISEASE OF

MUSCULOSKELETAL AND SKELETAL

MUSCLE

dr. Dyah Marianingrum ,Mkes,Sp.PA

 TRANSMISSION PATTERNS OF SINGLE-GENE
DISORDERS
Mutations involving single genes typically follow one
of three patterns of inheritance: autosomal dominant,
autosomal recessive, and X-linked.
• Autosomal dominant disorders are
manifested in the heterozygous state, so at
least one parent of an index case is usually
affected; both males and females are
affected, and both can transmit the
condition. When an affected person marries
an unaffected one, every child has one
chance in two of having the disease.
 Autosomal Recessive Disorders
Autosomal recessive traits make up the largest category of
mendelian disorders. Because autosomal recessive disorders
result only when both alleles at a given gene locus are mutated

features generally apply to most autosomal recessive disorders and

distinguish them from autosomal dominant diseases:

• The expression of the defect tends to be more uniform than in

autosomal dominant disorders

• Onset is frequently early in life.

 X-Linked Disorders
All sex-linked disorders are X-linked, and almost all are recessive.
Several genes are located in the “male-specific region of Y”; all of
these are related to spermatogenesis.
Males with mutations affecting the Y-linked genes are usually infertile,
 »Congenital Anomalies

• Congenital anomalies are morphologic defects that are present at birth,

but some, such as cardiac defects and renal anomalies, may not become
clinically apparent until years later.

• The term congenital means “born with,” but it does not imply or exclude a
genetic basis for the birth defect.

• It is estimated that about 120,000 (1 in 33) babies are born with a birth
defect each year in the United States. T

• the most common cause of mortality in the first year and contribute
significantly to morbidity and mortality throughout the early years of life.
 • Tumors and Tumor-like Lesions of Infancy and
Childhood

Only 2% of all malignant tumors occur in infancy and

childhood; nonetheless, cancer (including leukemia)
accounts for about 9% of deaths in the United States in
children over age 4 and up to age 14, and only accidents
cause significantly more deaths.
Benign tumors are even more common than cancers.
Most benign tumors are of little concern, but on
occasion they cause serious complications by virtue of
their location or rapid increase in size.
 BENIGN TUMORS AND TUMOR-LIKE LESIONS
• Hemangioma.
• the most common tumors of infancy.
• cavernous and capillary hemangiomas may be encountered,
although the latter are often more cellular than in adults, a
feature that is deceptively worrisome.
• In children, most are located in the skin, particularly on the
face and scalp, where they produce flat to elevated, irregular,
red-blue masses; some of the flat, larger lesions (considered
by some to represent vascular ectasias) are referred to as port-
wine stains.
• Hemangiomas may enlarge along with the growth of the
child, but in many instances they spontaneously regress
Congenital capillary
hemangioma at birth
(A)and at age 2 years
(B) after spontaneous
regression
 • Teratomas.
• Teratomas illustrate the relationship of histologic maturity
to biologic behavior.
• They may occur as benign, well-differentiated cystic lesions
(mature teratomas), as lesions of indeterminate potential
(immature teratomas), or as unequivocally malignant
teratomas (usually admixed with another germ cell tumor
component such as endodermal sinus tumor) .
• They exhibit two peaks in incidence: the first at
approximately 2 years of age and the second in late
adolescence or early adulthood.
• The first peak are congenital neoplasms; the later occurring
lesions may also be of prenatal origin but are more slowly
growing.
• Sacrococcygeal teratomas are the most common teratomas
of childhood, accounting for 40% or more of cases
• frequency of 1 in 20,000 to 40,000 live births, and are four times
more common in girls than boys.
• 10% of sacrococcygeal teratomas are associated with congenital
anomalies, primarily defects of the hindgut and cloacal region
and other midline defects (e.g., meningocele, spina bifida) not
believed to result from local effects of the tumor.
• Approximately 75% of these tumors are mature teratomas, and
about 12% are unequivocally malignant and lethal.
• The remainder is immature teratomas; their malignant potential
correlates with the amount of immature tissue, usually immature
neuroepithelial elements, present.
• Most of the benign teratomas are encountered in younger infants
(<4 months), whereas children with malignant lesions tend to be
somewhat older. Other sites for teratomas in childhood include
the testis ,ovaries and various midline locations, such as the
mediastinum, retroperitoneum, and head and neck.
Sacrococcygeal
teratoma.
 MALIGNANT TUMORS
Cancers of infancy and childhood differ biologically and
histologically from their counterparts occurring later in life.
• The main differences, some of which have already
been alluded to, include the following:
• Incidence and type of tumor
• Relatively frequent demonstration of a close
relationship between abnormal development
(teratogenesis) and tumor induction (oncogenesis)
• Prevalence of underlying familial or genetic
aberrations
• Improved survival or cure of many childhood tumors,
so that more attention is now being devoted to
minimizing the adverse delayed effects of
chemotherapy and radiation therapy in survivors,
including the development of second malignancies
ATPase, adenosine triphosphatase; NADH-TR, nicotinamide adenine dinucleotide, reduced
form, tetrazolium reductase
A, ATPase histochemical staining, at pH 9.4, of normal muscle showing
checkerboard distribution of intermingled type 1 (light) and type 2
(dark) fibers. B, In contrast, fibers of both histochemical types are
grouped together after reinnervation of muscle. C, A cluster of
atrophic fibers (group atrophy) in the center (arrow).
 Diseases of Skeletal Muscle
• Morphology
• The typical histologic finding in muscle is large
numbers of atrophic fibers, often only a few
micrometers in diameter
• This is unlike the groups of angulated atrophic
fibers seen in denervation atrophy of muscle in
adults.
• In SMA the muscle fiber atrophy often involves an
entire fascicle, a feature known as panfascicular
atrophy.
• There are also scattered large fibers that are two
to four times normal size.
Spinal muscular atrophy with groups of round atrophic muscle
fibers, or panfascicular atrophy, resulting from denervation atrophy.
 MUSCULAR DYSTROPHIES

The muscular dystrophies are a heterogeneous group of inherited

disorders of muscle, often beginning in childhood, that lead to
progressive weakness and muscle wasting.
Histologically, in advanced cases muscle fibers undergo
degeneration and are replaced by fibrofatty tissue and collagen
Duchenne
muscular
dystrophy
(DMD)
showing
variation in
muscle fiber
size, increased
endomysial
connective
tissue, and
regenerating
fibers (blue
hue).
• INFLAMMATORY MYOPATHIES
• There are three subgroups of inflammatory
muscle diseases: infectious, noninfectious
inflammatory, and systemic inflammatory
diseases that involve muscle along with other
organs
A, Dermatomyositis. Note the heliotrope rash affecting the eyelids. B,
Dermatomyositis. The histologic appearance of muscle shows
perifascicular atrophy of muscle fibers and inflammation.
C, Inclusion body myositis showing a vacuole within a myocyte.
TERIMA KASIH