DWARFISM AND GIGANTISM

1. Description
2. Etiology
3. Pathophysiology
4. Signs and symptoms
5. Diagnostic Tools
6. Medical management
7. Pharmacological management
8. Nursing management

DWARFISM
https://www.statpearls.com/ArticleLibrary/viewarticle/20778
 Description
 Types
 Etiology
 Signs and symptoms
 Medical management
 Pharmacological management
 Nursing management
Description
 Person with short stature (adult height of 4”10 or under) due to genetic or medical
reasons
o Other groups extend the criteria for certain forms of dwarfism to 5 feet
o Average height of an adult with dwarfism: 4 feet
 Some people prefer the term “short stature” or “little people” rather than “dwarf” or
“dwarfism”. So it is important to be sensitive to their preference of someone who
has this disorder.


TWO MAIN CATEGORIES

1. Disproportionate Short Stature (DSS)

 An average-sized torso and shorter arms and legs
o Normal yung size ng torso like that of normal human, pero maiksi mga
extremities
 Shortened trunk with longer limbs
 Usually, the head is disproportionately large compared with the body.

2. Proportionate Short stature (PSS)

 Body parts are in proportion with one another, but shortened.

ETIOLOGY
The short stature can either be due to an underlying medical condition or a standard variant of
growth. FSS, CDGP, and ISS described below can be considered as normal variants of growth, while
the rest are pathological causes-

1. Familial Short Stature (FSS): The child's genetic height potential can be measured by
measuring the mid-parental height, which is a child's projected adult height based on parental
height measurements. A positive family history, and the absence of underlying pathological
etiologies of dwarfism, can be diagnosed as a case of familial short stature. This child has an
expected growth velocity, and his bone age is consistent with the chronological age. X-Ray of the
hand and wrist can establish the bone age and is a frequently used modality.

2. Constitutional delay of growth and puberty (CDGP): The child presents with short height in
childhood, but attain their target height until adulthood, also known as a 'late bloomer'. They
even enter puberty at later ages. Unlike in familial cases, these children have bone age lagging
behind the chronological age. Malnutrition in gestational age or childhood, even genetics, could be
the plausible cause for this short stature pattern.

3. Idiopathic Short Stature (ISS): Short stature is said to be idiopathic when no other etiology like
endocrine/metabolic can be determined. With the advancements in genomic studies, it is found
that many cases previously established as idiopathic can be explained by hundreds of genetic
mutations with small or large effects. The role of epigenetics is also in discussion.

4. Endocrine disorders: Growth hormone deficiency is a frequent cause of dwarfism. The

hypothalamic-pituitary axis maintains the levels of growth hormones in the body, which then
directly or indirectly, through Insulin-like growth factor-1 (IGF-1), stimulates bone elongation, and
growth of soft tissue and cartilage. Lower levels of IGF-1 are linked with short stature. Precocious
puberty is defined as the attainment of puberty before the age of 8 years in girls and nine years in
boys due to the premature release of gonadotropins centrally or peripherally. These
gonadotropins lead to an initial growth spurt but also lead to the early maturation of the child's
skeletal system resulting in short adult height

5. Genetic disorders: Many genetic conditions that are associated with short stature are- Down's,
Turner's, Noonan's, 3-M, Prader-Willi, Russell-Silver, Aarskog, and short stature homeobox gene
deficiency syndrome. Short stature is one clinical manifestation among several others.

a)Turner syndrome
o Missing X chromosome on the 23rd pair
o Genetic condition only affecting females
o Girls with this condition only inherit one fully functioning X chromosome from their
parents, instead of one from each parent.
o Becomes evident about 5 years of age
6. Bone diseases: The faulty formation of bone can also lead to short stature. The bone disorders
linked to dwarfism are-

Conditions under skeletal dysplasia

b) Achondroplasia
o The most common form of dwarfism—accounting for 70% of the cases
o Relatively long trunk and shortened upper parts of their arms and legs
o Large head with prominent forehead
o Flattened bridge of the nose
o Protruding jaw
o Crowded and misaligned teeth
o Forward curvature of the lower spine
o Bowed legs
o Flat, short, broad feet
o “Double-jointedness”

c) Spondyloepiphyseal dysplasia (SED)

o Less common form
o Shortened trunk, which may not become apparent until a child is between 5-10
years old
o Club feet
o Cleft palate
o Severe osteoarthritis in the hips
o Weak hands and feet
o Barrel-chested appearance

d) Diastrophic dysplasia
o Rare form of dwarfism
o Mesomelic shortening
o Shortened forearms and calves
o Deformed hands and feet
o Limited range of motion
o Cleft palate
o Ears with cauliflower appearance

7. Systemic disorders: Other systemic diseases which have a secondary effect on growth are

undernutrition, juvenile idiopathic arthritis, inflammatory bowel disease (IBD), celiac disease,
chronic kidney disease (CKD), pulmonary/cardiac/immunologic/metabolic diseases, cancers, and
glucocorticoid therapy.[5][6][7] Malnutrition can dampen the growth velocity and cause short
stature. It can affect the baby in the gestational period, leading to underweight or small for
gestational age (SGA) baby, or in childhood leading to stunted growth.[8]

SYMPTOMS
1. Disproportionate Dwarfism
 Does not affect intellectual development of a child, unless they have other rare
conditions, such as hydrocephalus (excess fluid in the brain)
 Height of 4 ft in average
 Average-size torso and very short limbs, especially in the upper halves of arms and
legs
 Short digits (Brachydactyly)
 Wide spaces between the middle and ring fingers
o Trident sign
 Limited elbow mobility
 Disproportionately large head
 Prominent forehead
 Flattened bridge of the nose
 Bowing of the legs the progressively worsens over time (Genu varum)
 Swaying of the back that progressively worsens over time (“Spinal Lordosis”)

a) Spondyloepiphyseal Dysplasia Congenita (SEDC)

 Also around 3-4 ft in average
 Very short trunk
 Short neck, arms, and legs, but average-size hands and feet
 Broad chest
 Flattened cheekbones
 Cleft palate, or an opening in the roof of the mouth
 Unstable neck bones
 Deformed hips where thigh bones turn inwards
 Twisted feet
 Hunched upper back that progressively worsens
 Swayed lower back that progressively worsens
 Arthritis
 Joint mobility problems
 Impaired vision or hearing

2. Proportionate Dwarfism
 Medical condition that you have at birth or that develops in childhood that hinders
growth or development
o Develops during childhood: kala mo normal ‘yung anak mo kasi nga
proportionate naman pag-develop ng extremities, pero mabagal lang due to
growth hormone deficiency
 Common cause: Too-low amounts of growth hormone produced by your pituitary
gland
 Smaller head, arms, and legs, but all are in proportion with each other. Organ system
may be smaller too.
 Slower growth rate than expected for their age
  Height lower than the third percentile on standard charts for age
 Delayed or no sexual development during the teenage years

DIAGNOSIS
 Some forms of dwarfism are evident in utero, at birth, or during infancy
 Can be diagnosed through X-Rays and a Physical Exam
 Genetic testing – diagnosis for achondroplasia, diastrophic dysplasia, or
spondyloepiphyseal dysplasia
 Sometimes, dwarfism does not become evident until later in a child’s life, when
dwarfism signs lead to parents seek a diagnosis
 Appearance. Changes to their skeleton or facial structures as they develop. Many
distinct fa
 Chart comparisons. At regular check ups, your child’s height, weight, and head
circumference will be measured and compared to percentiles for standard
development for their age. If your child shows any signs of abnormal growth, they
may need more frequent measurements to confirm.
 Imaging. Doctors may spot signs of achondroplasia, such as shorter limbs, or other
causes of dwarfism on ultrasounds of a fetus during pregnancy. X-rays of babies or
children may show that their arms or legs are not growing at a normal rate, or that
their skeleton shows signs of dysplasia. MRI scans can show any abnormalities of
the pituitary gland or hypothalamus, which affect hormone production.
 Genetic testing. DNA tests may be done before or after birth to look for genetic
mutations linked to dwarfism. Girls with suspected Turner syndrome may need
DNA tests to check their X chromosomes. DNA testing may help parents with family
planning if they wish to have more children.
 Family history. Pediatricians may check the height and size of other family
members, such as siblings, to compare with child of suspected dwarfism.
 Hormone tests. Tests of GH levels can confirm if they are low.

MEDICAL MANAGEMENT
 Early diagnosis and treatment can help prevent or lessen some of the problems
associated with dwarfism.
 In many cases, people with dwarfism have orthopedic or medical complications.
Treatment of those include:
o Ventriculoperitoneal shunting
 Insertion of a shunt to drain excess fluid and relieve pressure on the
brain
o Tracheotomy to improve breathing through small airways
o Corrective surgeries for deformities such as cleft palate, club foot, or bowed
legs
o Tonsillectomy or adenoidectomy
 Surgery to remove tonsils or adenoids to improve breathing problems
r/t large tonsils, small facial structures, and/or a small chest
o Foraminotomy
  Surgery to widen the spinal canal (the opening through which the
spinal cord passes) to relieve spinal cord compression
o Extended limb lengthening, a controversial surgery, due in part to its risks,
involves several procedures. It is only done on adults.
 Other treatments:
o Physical therapy to strengthen muscle and increase joint range of motion
o Back braces to improve curvature of the spine
o Placement of drainage tubes in the middle ear to prevent hearing loss due to
repeated ear infections
o Orthodontic treatment to relieve crowding of teeth caused by a small jaw
o Nutritional guidance and exercise to help prevent obesity, which can
aggravate skeletal problems

 Some people with dwarfism choose to undergo surgery called extended limb
lengthening. This procedure is controversial for many people with dwarfism
because, as with all surgeries, there are risks. Waiting to decide about limb
lengthening until the person with dwarfism is old enough to participate in the
decision is recommended because of the emotional and physical stress involved
with multiple procedures.

*Most of the time, women with disproportionate dwarfism may have pregnancy
complications, such as respiratory problems. They almost always need to deliver their
babies by C-section, as the shape of their pelvis makes VAGINAL DELIVERY too difficult.

PHARMACOLOGICAL MANAGEMENT
 People with dwarfism r/t GH deficiency can be treated with growth hormone.
o Responsible for linear skeletal growth, growth of internal organs, protein
synthesis, and stimulation of processes required for normal growth.
o Such as growth hormone agonists, like Somatropin (Nutropin, Saizen,
Humatrope)
o In most cases, children receive daily subcutaneous injections for several
years until they react a maximum adult height—often within the average
adult range for their family.
o Treatment may continue throughout the teenage years and early adulthood
to ensure adult maturation, such as appropriate gain in muscle or fat.
 Preferably within 1 hour before bedtime every night, at a specific
time, and not to miss more than one dose monthly.
 Patient usually follows up 2-4 times a year
 Growth rate is maximum in the first year of treatment, ranging from
8-10 cm/year—this is called “Catch-up growth”.
 This growth rate slows in the next several years, called “Warning
effect”
  If the growth rate is slower thn expected, it warrants further
investigation to rule out other medical conditions, such as
hypothyroidism or IBD.
o Some individuals may need life-long therapy. The treatment may be
supplemented with other related hormones if they are also deficient.
 For children 5 years of age and older with achondroplasia who still have the
potential for growth, the FDA has approved vosoritide (Voxzogo) to help stimulate
bone growth.
o First FDA approved drug to improve growth in genetic cause dwarfism
 Treatment for girls with Turner syndrome also requires estrogen and related
hormone therapy in order for them to begin puberty and achieve adult sexual
development. Estrogen replacement therapy usually continues throughout life until
women with Turner syndrome reach the average age of menopause.

NURSING MANAGEMENT
For growth hormone therapy, inform patients of the following:

 The GH used in treatment is similar to GH released from the pituitary gland and is safe
and effective.
 The patient can experience foot growth within 6-8 weeks of treatment, increase
appetite, increase lean body mass, and decrease fat. 
 Long term commitment to the treatment.
 Importance of compliance for best outcomes.
 The patient needs to be informed about the administration technique, injection sites,
timings, and the drug's refrigerating requirements for optimum efficacy.
 The possible side effects- 
o Allergic reaction, rash, or swelling at the injection site.
o Hip, knee, or other joint pain indicative of slipped capital femoral epiphysis.
o Headache may be indicative of benign intracranial hypertension.
o Progression of scoliosis.
o Temporary increase in blood sugar levels. Management of these complications
can be done by temporary therapy termination until resolving symptoms and
restarting later at lower doses.

COLLABORATIVE
  Routine consults with the pediatric endocrinologist, blood test, and X-ray to monitor
the child's progress.
 Regular counseling sessions help to educate the patient and family members and improve
the outcomes. The psychologist and psychiatrist may need to intervene in children facing
psychosocial stressors, eating disorders, and other mental illnesses.

ACHONDROPLASIA
 Autosomal dominant genetic condition
 Most common cause of dwarfism
 Heterozygous mutation: FGFR 3 (Fibroblast Growth Factor Receptor 3)
o Located on chromosome 4
 Codes for the FGFR3 Protein

FGFR3 PROTEIN
 When this binds FGFs, it slows down the growth of certain bones
 The mutation causing achondroplasia is almost always the 380th amino acid,
GLYCINE, getting swapped out for ARGININE in the FGFR3 receptor.
o This swap causes the FGFR3 receptor to be constitutively active.
o Dahil nga nagkapalit yung dalawang amino acids, nagiging active yung FGF3
which inhibits the growth of certain bones.
o The mutation makes the receptor behave as though it is binding an FGF even
when it is not, which sends a strong signal to inhibit bone growth.

FGFR3 MUTATION
 “Always on” causes chondrocytes at the growth plate to proliferate slowly and
become disorganized.
o Mostly affects ENDOCHONDRAL BONE FORMATION
  Process of bone forming on previously-laid-down cartilage matrix,
which causes the bone to elongate.
 With the mutation, this elongation of the NEW BONE is inhibited,
which means long bones like HUMERUS and PHALANGES are
affected.
 Affects the ENDOCHONDRAL BONE FORMATION, but bones that are products of
INTRAMEMBRANOUS BONE FORMATION are way less affected.
o Where bones grow without an existing cartilage matrix.
 Eg. Flat bones – skull, sibs
 Eg. Appositional growth – process of widening of long bones

DWARFISM
 Result of shortened long bones with disproportionate short stature
 The limbs are short while the trunk and head size is largely preserved.
o Specific long bone defects include: rhizomelic (proximal), shortening of the
limbs, varus leg deformity (“Knees Out”), short metacarpals creating a broad
hand, and short phalanges causing brachydactyly (“Short fingers”)
o When outstretched, the fingers form a “Trident hand”, where the tips of the
fingers cannot touch each other.
o Flat bone defects, although less pronounced, do exist, and can include: large
head size, frontal bossing, flattened nasal bridge, a narrow foramen magnum,
and spinal lordosis.
 Although there are a lot of changes to the skeleton, a person’s other organs,
intelligence, lifespan, and fertility are all normal.

DIAGNOSIS (Achondroplasia)
  Long bone shortening is often pronounced enough that achondroplasia can be
diagnosed by prenatal ultrasound.
o The ratio of skull width (biparietal diameter) to femur length in this case is
higher normal
 DNA Test
o Can conform the diagnosis either before or after birth
 Skeletal survey
o A series of X-rays that capture much or all of the skeleton
o Might also confirm other skeletal dysplasia
 A blanket term for disorders of skeletal development, of which there
are hundreds of types in addition to achondroplasia.
 ACHONDROPLASIA – most common skeletal dysplasia
 Reason: has very high new mutation rate
o New/De Novo – the mutations come from the father,
and get more frequent with increased paternal age, since
the sperm progenitor cells have more and more time to
acquire mutations

HETEROZYGOUS MUTATION
 They have one copy of the FGFR3 gene with the mutation, but the other copy is
normal.

*What if both mom and dad have achondroplasia, and they happen to both contribute an
FGFR3 mutation to the child?
 LEADS TO HOMOZYGOUS ACHONDROPLASIA
o An extremely severe form of the disease that is lethal before or shortly after
birth.
*What if neither of the parents transmit their FGFR3 mutation?
 Then the child would not have achondroplasia.
Notes:
 Only a few forms of dwarfism and gigantism can normally be diagnosed at a glance.
One example is achondroplasia (Figure 1), with its rhizomelic dwarfism, the typical
head with a prominent forehead, saddle nose and prominent chin, the trident hand,
the jutting buttocks due to hyperlordosis and often bow-legs4.
 cretinism or hypothyroid dwarfism Figure 1 Martha Ulirich (left) on horseback, 23
years old, 98cm (spondyloepiphyseal dysplasia), and Franzi Frohlich (right), 32
years old, 105 cm (achondroplasia). Between them a normal woman Figure 2 The
brothers Hugo, both of them 230 cm, and Adrien, 69cm (acromegalic giants;
hypopituitary dwarf) (Figures 2 and 3) with a round face, flat nose and squashed
root of the nose and wrinkled skin. The short limbs lend the body infantile
proportions. The so-called bird-headed dwarf is a very striking phenotype of 274
microcephalic primordial dwarfism
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296707/pdf/jrsocmed00025-
0045.pdf

TREATMENT
 There is not any generally accepted way to increase height at the present time

GIGANTISM
 “Giant”
 Rare hormonal disorder in children and adolescents where there is an excess of
growth hormone, and it causes rapid and excessive growth of long bones, like the
tibia and humerus.
 A condition of a person that causes excess growth with a large height above normal
and is caused by the secretion of excessive GH and occurs before adulthood or
before the closure of the epiphyseal plates.
 Treatable, but early diagnosis is crucial to prevent excessive height and other
complications.
 Aka “Pediatric acromegaly” and “Pituitary Gigantism”
 The pituitary gland normally produces GH, but a tumor on their pituitary can
produce excess GH in gigantism.

ACROMEGALY
 A disorder of excess growth hormone in adults
o Long bones have already stopped growing

GROWTH HORMONE
 Aka “Somatotropin”
 Normally, the hypothalamus (located at the base of the brain) secretes growth
hormone-releasing hormone in bursts throughout the day — every couple of hours,
 and this can increase based on things such as: low blood glucose levels, lack of food,
increased exercise, increased sleep, and increased stress (eg. trauma).
 The growth hormone-releasing hormone goes into the hypophyseal portal
system
 Network of capillaries linking the hypothalamus to the anterior
pituitary which is smaller in size than a pea
o Binds to a surface protein on the somatotroph and mammosomatotroph cells
of the anterior pituitary gland, and in response, they release growth
hormone.
 Direct effects:
o Tissues where GH stimulates cellular metabolism that leads to organ growth
 Liver releases more glucose into the blood
 Body retains nitrogen leading to more muscle growth
 Osteoblasts get stimulated which causes the bones to thicken
o Increase insulin resistance making it harder for cells to take in glucose, which
leads to an increase in blood insulin levels.
 Similar to what happens in patients who have diabetes, this effect of
growth hormone is called DIABETOGENIC.
 Hindi nagagamit yung glucose ng blood for energy.
 Indirect effects:
o Growth hormone stimulates certain tissues like the liver, bone, skeletal
muscles, and kidneys to produce somatomedin C (“Insulin-like Growth
Factor 1”)
 Promotes cellular metabolism, prevents cell death, and helps cells
divide and differentiate in the body
 The key hormone that stimulates the growth in length of long bones

CAUSES
 Pituitary adenoma
o Which specifically involves the mammosomatotroph cells (“somatotroph
cells”) in the anterior pituitary gland
o Usually a benign tumor which does not invade into the neighboring tissues
o These tumor cells continuously make excess growth hormone and that in
turn leads to excess insulin-like growth factor 1 as well.
 Pituitary hyperplasia
o Pituitary gland becomes enlarged
 Hypothalamic tumor
o Tumor sa hypothalamus
o Releases too much growth hormone-releasing hormone
 Other tumors that produce GH ectopically
o Cells in the pituitary are secreting lots of growth hormone simply because
they are being overstimulated.
 McCune Albright Syndrome
 o Genetic condition that affects your bones, skin, and endocrine system,
causing café-au-lait skin pigmentation, scar tissue formation on bones and
early puberty
o Genetic condition which causes overproduction of several hormones
including GH
o Often caused by pituitary hyperplasia or pituitary adenomas
 Familial isolated pituitary adenomas (FIPA)
o An inherited condition characterized by the development of pituitary
adenomas, which can include GH-secreting adenoma

SYMPTOMS
 Appear dramatically (happens suddenly) because children’s bodies are very
responsive to growth hormone and insulin-growth factor 1.
o Excessively fast growth in height
o Rapid weight gain
 Because of excess insulin-growth factor 1.
o Macrocephaly
 Enlargement of skull bones
 Prominence of forehead
o Projection of the lower jaw
o Gaps between the teeth
o Thickening of facial features
o Soft tissues swelling in the hands and feet
o Increased size of organs (eg. heart)
o Excessive sweating (hyperhidrosis)
o Double vision or difficulty with peripheral vision
o Joint pain
o Sleep apnea
o Muscle weakness
 Additional problems:
o Carpal tunnel syndrome
 Due to increased pressure on nerves from muscle growth
o Diabetes mellitus from the diabetogenic effects of GH
 If ETIOLOGY is MAMMOSOMATOTROPH CELLS:
o Excess of prolactin
 Hormone that stimulates the production of breast milk,
 This happens because the mammosomatotroph cells make
both prolactin and GH.
 Decreased menstruation in adolescent girls
 Enlarged breasts in adolescent boys
 Headaches
 Compression of the optic nerve
DIAGNOSIS
 Can be made if there are increased levels of insulin-growth factor 1 (IGF-1) and
growth hormone (Blood tests)
o Particularly if the levels of growth hormone are elevated in spite of receiving
large dose of glucose
 High levels of prolactin (if mammosomatotroph cells are involved)
 MRI
o Confirms the diagnosis of a pituitary tumor by showing the size and location
of a pituitary tumor
 Glucose tolerance test
o Can assess whether the child’s GH levels react to glucose the way they should
o A provider will draw blood samples from the vein at different intervals after
the child drinks a glucose solution
 Echocardiogram
o To check for heart issues
 Sleep study tests
o To check for sleep apnea
 XRAY
o To check for bone health

TREATMENT
 Transsphenoidal Surgery
o To remove the pituitary adenoma or other tumors that are causing the
disorder
 Medications
o Somatostatin analogs
 Limits GH production or GH receptor antagonists which stop growth
from binding to target tissues
 Radiation therapy
o Rarely used because risks are high for children and adolescents