Thirty Two Flashcards
What is Aplasia Cutis congenita?
a. Aplasia Cutis Congenita: Localized absence of skin, usually on scalp.
Often part of another syndrome.
Describe ichthyosis. Patholgenesis? What is harlequin fetus? Collodion baby?
b. Ichthyosis (Ichthy: Fishy): Heterogeneous group of disorders of
keratinization with increased cell-cell adhesion resulting in abnormal
desquamation, have excessive skin keratin (hyperkeratosis). Defective
desquamation leads to retention of abnormal scale. Often inherited. Dry,
fish-skin-like skin scales, involve entire body surface. Most patients
present at birth.
i. Harlequin fetus: Rare, AR, thick-ridged cracked skin. Often die in first week of life but there are long term survivors.
ii. Collodion baby: Covered by a thick, taut membrane, the skin surface resembles collodion, cracks with first respiratory effort, may shed and leave behind normal skin.
Describe a cystic hygroma. Describe a hemangioma.
c. Vascular anomaly: Developmental defect of blood or lymphatic vessels.
i. Cystic Hygroma: Angioma of lymphatics. Benign tumor of lymphatics. The tumor margins are not discrete and
unencapsulated making definitive resection difficult.
ii. Hemangioma: Most common tumor in infants, children, benign endothelial cell tumor, can spontaneously regress,
What is albinism? Pathogenesis? What is piebaldism? Pathogenesis?
d. Albinism: AR, skin, hair, and retina lack pigment, melanocytes fail to
produce melanin because of lack of enzyme tyrosinase which is necessary
for the synthesis of melanin from its precursor tyrosine.
i. Piebaldism: AD, localized “albinism” “White Forelock”, lack of melanin in patch of skin or hair. Can be caused by mutation in the KIT protooncogene, encoding a tyrosine kinase receptor involved in pigment cell development
What is arthrogryposis multiplex congenita? Etiology? Describe Congenital torticollis.
a. Arthrogryposis multiplex congenita: Fetal Akinesia-Hypokinesia Sequence. Failure of normal muscle development, widespread joint contractures, all associated with decreased fetal movement.
i. Neurogenic
ii. Myopathic
iii. Amyoplasia
b. Congenital torticollis (wry neck): Injury to the sternocleidomastoid (SCM) muscle with fixed rotation, tilting of the head, because of fibrosis of SCM muscle.
What are limb reduction deficits? How can they be treated? Location? Etiologies? What is amelia? pathogenesis? Meromelia? Pathogenesis? Describe ectrodactyly. Describe congenital absence of the radius.
a. Limb reduction defects. 1/500, may be surgically correctable. May indicate a more serious anomaly or defect pattern. 75% of limb reduction defects affect upper extremity.
i. Etiology: 1. Genetic factors (eg: chromosomal anomalies, T18)
2. Mutant genes (eg: brachydactyly)
3. Environmental factors: Teratogen such as Thalidomide
taken between d 24-36 after fertilization caused amelia or
meromelia depending on when drug was ingested.
4. Genetic + Environmental (multifactorial)
5. Vascular disruption and ischemia (eg: amniotic band
sequence)
ii. Amelia: Complete absence of limb. Due to suppression of limb bud development during the early part of wk 4.
iii. Meromelia: Partial absence of limb. Due to arrest or disturbance of differentiation or growth during wk 5.
- Ectrodactyly: cleft hand/foot, lobster-claw deformity.
Absent central digits, failure of development of one or
more digital ray. - Congenital absence of the radius. Hand deviates laterally, due to failure of mesenchymal primordium
form during 5th week of gestation.
What is polydactyly? What is syndactyly?
i. Polydactyly: Supernumerary digit. Can be AD, the extra digit is not normally formed and lacks normal muscle, usually lateral or medial.
ii. Syndactyly: Webbing of digit, most common limb anomaly. Due to incomplete programmed cell death (apoptosis) of the tissues between the digital rays. In severe cases there is fusion of bones.
Describe the oligohydramnios sequence. pathogenesis? Describe the amniotic band sydrome and pathogenesis.
c. Limb Deformation/Disruption Syndromes
i. Oligohydramnios sequence: Affected children have talipes (club foot), a deformity of foot involving talus (ankle), 1/1000, abnormal position of foot, prevents normal weight bearing, walk on the ankle, may be caused by abnormal positioning or restricted movement of the fetus limbs in utero, as in occurs in oligohydramnios sequence.
ii. Amniotic Band Syndrome: Amnion tear results in constriction or amputation of a developing limb or
body part.
What is the pathogenesis of achondroplasia? Genetics? Clinical features?
A. Impaired cartilage proliferation in the growth plate; commo n cause of dwarfism f! Due to an activating mutation in fibroblast growth factor receptor 3 (FGFR3);
autosomaldominant
1 , Ove rex press ion of FGFA3 inhibits growth.
2. Most mutations are sporadic and related to increased paternal age.
C. Clinical features
I Short extremities with normal-sized head and chest—due to poor endochondral
bone formation; intramembranous bone formation is not affected.
i. Endochondral bone formation is characterized by formation of a cartilage matrix, which is then replaced by bone; it is the mechanism by which long
bones grow.
ii. Intramembranous bone formation is characterized by formation of bone without a preexisting cartilage matrix; it is the mechanism by which fiat bones (e.g., skull and rib cage) develop.
D. Mental function, life span, and fertility are not affected,
What is thanatophoric dwarfism? Common result? Pathogenesis? Clinical features?
g. Thanatophoric dwarfism: Most common lethal dwarfism. 1/20,000, die with respiratory insufficieny secondary to pulmonary hypoplasia.
i. Pathogenesis: Mutation in FGFR3, different than achondroplasia. Caused by a gain-of- function mutation in F GFR 3.
ii. Pathology: Short limbs (micromelia), relative macrocephaly, frontal bossing, small chest cavity which leads to respiratory insufficiency. The histologic changes in the growth plate show diminished proliferation of chondrocytes and poor columnarization in the zone of proliferation.
What is the pathogenesis of the two main types of OI? Genetics of OI? Clinical features? Pathology?
h. Osteogenesis Imperfecta (Brittle Bone Disease): Heterogeneous group of
phenotypically related congenital diseases, defect in synthesis and
assembly of Type I procollagen by osteoblasts. Over 800 mutations have
been identified in the genes that encode for the alpha-1 and alpha-2 chains
of collagen. The most common inherited disorder of connective tissue.
Type I collagen makes up 90% of organic matrix in bone. All sites with
Type I collagen are affected (bone, joint, eye (causes blue sclera), ear
(causes deafness, due to both a sensorineural deficit and impeded
conduction due to abnormalities in the bones of the middle and inner ear),
skin and teeth (have small misshapen and blue yellow teach due to
deficiency of dentin)). Often AD, four major subtypes, all have extreme
bone fragility. 1/10,000.
i. Pathogenesis: Mutation in gene that codes for 1 or 2 chains of
ii. Pathology: Too little bone, i.e., osteopenia with marked cortical
type I collagen.
- Mutations that result in production of qualitatively normal
collagen synthesized in decreased amounts are associated
with mild skeletal abnormalities.
- Lethal phenotype Type II OI is result of genetic defects
producing abnormal collagen chains than don’t form the
collagen triple helix.
thinning, attenuation of cortex trabeculae. Have short bowed long
bones, small thorax, and multiple fractures because of fragile
skeleton.
What is osteopetrosis? Pathogenesis? Clinical features? Pathology?
A. inherited defect of bone resorption resulting in abnormally thick, heavy bone that
fractures easily
H. Due to poor osteoclast function
C. Multiple genetic variants exist; carbonic anhydrase II mutation leads to loss of the
acidic microenvironment required for bone resorption.
D. Clinical features include
L Bone fractures
2. Anemia, thrombocytopenia, and leukopenia with extramedullar)’hematopoiesis—due to bony replacement of the marrow (myelophthisic process)
3 . Vision and hearing impairment—due to impingement on cranial nerves
4. Hydrocephalus—due to narrowing of the foramen magnum
5. Renal tubular acidosis—seen with carbonic anhydrase II mutation
i. Lack of carbonic anhydrase results in decreased tubular reabsorption of HCO, , leading to metabolic acidosis.
Bone fractures occur in both AD and AR versions. The rest usually occurs more in AR version.
E. Treatment is bone marrow transplant; osteoclasts are derived from monocytes.
iii. Pathology: Radiopaque bones lack medullary cavity. Sheets of
abnormal osteoclasts or fibrosis replace marrow. Patients have no
hematopoietic marrow and have extramedullary hematopoiesis.
They lack mature trabeculae; ends of long bones are bulbous. The
widened metaphysis and diaphysis give the bone an “Erlenmeyer
flask” deformity. Cortex is thickened. The bones are intrinsically
disorganized, do not remodel along lines of stress and fracture
easily.
What is ricketts? What is the pathogenesis? Etiologies? Epidemiology? Symptoms?
A. Detective mineralization of osteoid
I. Osteoblasts normally produce osteoid, whic h is then mineralized with calcium
and phosphate to form bone.
B. Due to low levels o f v i t a m i n D, which results in low serum calcium and phosphate
1 . Vitamin D is normally derived fro m the skin upo n exposure to sunlight (85%) and fro m the diet (15%).
2. Activation requires 25-hydroxylatton by the liver followed by 1-alphahydroxylatton by the proximal tubule cells of the kidne y
3 . Active vitamin D raises serum calcium and phosphate by acting on
i. Intestine—increases absorptio n of calcium and phosphate
i i. Kid ney— increases reab so r p t i o n o f c a l c i u m a n d phosphate
iii. Bone—Increases resorption of calcium and phosphate
- Vitamin D deficiency is seen with decreased sun exposure (e.g.. northern latitudes), poo r diet, malabsorption, liver failure, and renal failure.
C. Rickets is due to low vitamin D in children, resulting in abnormal hone mineralization.
1 . Most commonl y arises in children < 1 year of age; presents with
i. Pigeon-breast deformity—inward bending of the ribs with anterio r
protrusio n of the sternum
ii. Frontal bossing (enlarged lorehead)—due to osteoid deposition on the skull
iii. Rachitic rosary—due to osteoid deposition at the costochondral junctio n
iv. Bowing of the legs may be seen in ambulating children.
What is osteomalacia? symptoms? Lab findings?
D. Osteomalacia is due to low vitamin D in adults.
1 . Inadequate mineralization results in weak bone with an increased risk for
fracture.
2. Laboratory findings include decr. serum calcium, decr. serum phosphate, incr. PTH, and incr. alkaline phosphatase
What is craniosynostosis? Pathogenesis? Results?
e. Craniosynostosis: Due to premature closure of the skull sutures.
Boys>girls, results in skull deformation.
i. Sagittal suture closure leads to scaphocephaly: Long narrow wedge-shaped skull.
ii. Coronal suture closure leads to oxycephaly or turricephaly: High tower- like skull
