Fetal development Flashcards
How to determine the age of a baby?
- Last menstrual period
- Weight
- Height
- Organogenesis
- External characteristics
- Radiology
- Histology
Discuss types of birth defects
Causes:
- Chromosomal abnormalities
- Single gene defects - AD, AR, X-linked
- Multifactorial problems
- Teratogenic problems
Mechanisms
- Intrinsic: malformation or displasia
- Extrinsic: disruption or deformation
Category:
- Isolated defect: minor anomaly, major anomaly, sequence
- Multiple defects: syndrome, field defect, association
Define malformation
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Malformation: “Morphological defect of an organ ^[defect of organogenesis], or larger region of the body resulting from an intrinsically abnormal developmental process ^[blastogenesis abnormality].”
- Example: Absence of a thumb due to abnormality of the apical ectodermal ridge that controls limb bud development.
- Intrinsically abnormal implies a genetic cause (e.g., chromosomal abnormality, genetic predisposition/multifactorial determination, mendelian mutation, etc.)
Define dysplasia
Dysplasia: “Abnormal organization of cells into tissue(s) and its morphological result(s).” It is a process and consequence of dyshistogenesis.
- Example: Osteogenesis imperfecta and Marfan syndrome - defects of connective tissue.
Define disruption
“Morphologic defect of an organ, part of an organ or a larger region of the body resulting from extrinsic breakdown of, or an interference with, an originally normal process.”
- Example: Amniotic band that wraps around a developing limb and produces distal hypoplasia or amputation.
Define deformation
Deformation: “Abnormal form, shape or position of a part of the body caused by mechanical forces.” A normal response to abnormal forces and the affected structure after development. Potentially remediable post-natally, or can correct spontaneously.
- Example: Clubfoot – equinovarus deformity.
Define anomaly
“(Any) deviation from expected or average type in structure, form and/or function which is interpreted as abnormal.”
- Characterization of anomalies as “abnormal” distinguishes them from normal variants (>4% population)
Define major and minor anomalies
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Major Anomalies: Those with cosmetic or surgical consequences; e.g., deformed wrist, limb defect, neurofibromas, etc.
- Minor Anomalies: Despite their diagnostic importance have little impact on individual well-being; e.g., clinodactyly, single palmar crease, anteverted nares, hypertelorism, etc.
Define a sequence
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Sequence: “Cascade of primary and secondary events that are consequences of a single primary malformation or a disruption.”
- Sequences are isolated malformations are often associated with sporadic or multi-factorial inheritance.
Define a malformation sequence
An intrinsically abnormal developmental process
- Example: X-linked spina bifida/myelomeningocele sequence – secondary neurohypotrophy of lower limbs, club feet, neurogenic bladder with chronic urinary tract infection.
- Example: Di George (sequence/anomaly/complex) – Due to del(22)(q11) with presumed primary defect of neural crest involved in differentiation of face, branchial arches, conotryncal area of the heart with secondary hypoparathyroidism, immune defect, and cyanotic congenital heart defect.
Provide examples of dysplasia sequence
Sacrococcygeal teratoma complex with defective sacrum and coccyx, imperforate anus, rectovaginal fistula, and urinary tract obstruction
Provide examples of disruption sequence
Extrinsic interference
Example: Arterial disruption as performed in animal models to produce the asymmetric hypoplasia of the jaw known as hemifacial microsomia. Fetal constraint with severe torticollis can also produce the hemifacial microsomia
Provide examples of deformation sequence
Deformation Sequence due to mechanical forces
Example: Bilateral renal agenesis (Potter’s syndrome) with absence of Wolffian and Müllerian duct derivatives; hypoplasia or absence of the bladder; oligohydramnios with subsequent deceleration of growth; redundant skin; deformed limbs; nose, ears, and face; and pulmonary hypoplasia
* Fluid that foetus is kept in is essentially the baby’s urine ∴ without lugs there is less fluid
* Limbs don’t develop properly and get stuck to sides (webbing)
* Adrenal structures grow uncontrollably (not limited by kidneys below them)
* Lungs develop by swallowing amniotic fluid to expand and grow - lung hypoplasia usually fata
Define syndrome
“Multiple anomalies thought to be pathogenetically related and not representing a sequence.” Syndrome implies a lower level of a given pattern of pathogenetically related anomalies than a sequence.
Example: Down syndrome (Trisomy 21)
For interest: Trisomy 9
Define developmental field defects
“Result of (non-disruptive) disturbed development of a morphogenic field or pattern thereof,” or a “Dysmorphogenetically reactive unit, i.e., a set of embryonic primordia that reacted identically to different dysmorphogenetic causes.”
Connections between primary cause and multiple consequences less well defined than for sequences.
More reproducible consequences that are typical to syndromes.
