MSK - Genetics - Dysmorphology; Skeletal Dysplasia; Newborn Screenings; Inborn Metabolic Errors Flashcards
What are the ‘vital signs’ of dysmorphology?
Height, weight, and head circumference
Of newborns with structural defects, about 1/4 have multiple anomalies.
What is the singular leading cause of multiple anomalies in a newborn?
(note: only 50% of cases with multiple anomalies even have a known etiology)
Chromosomal abnormalities
(76% of known etiologies)
Do singlular anomalies in newborns typically have an identifiable etiology?
No;
they are typically multi-factorial
Define ‘sequence’ in terms of dysmorphology and congenital defects.
One anomaly leads to other developmental anomalies
(e.g. Potter’s syndrome)
What is the acronym for the signs of Potter’s syndrome?
POTTER
Pulmonary hypoplasia
Oligohydramnios
Twisted face
Twisted skin
Extremity abnormalities
Renal agenesis
Define ‘dysplasia’ in terms of dysmorphology and congenital defects.
Intrinsic developmental abnormality due to defective cellular organization
(e.g. skeletal dysplasia;
effects of fetal alcohol syndrome, thalidomide)
Define ‘disruption’ in terms of dysmorphology and congenital defects.
Interruption of normal morphological effects due to an extrinsic force
(e.g. amniotic band syndrome)
Define ‘deformation’ in terms of dysmorphology and congenital defects.
A change of normal morphology caused by extrinsic forces
(e.g. clubfoot)
Define an ‘association’ disorder in terms of dysmorphology and congenital defects.
An exclusion diagnosis of a nonrandom pattern of effects
(e.g. VACTERL, or CHARGE)
Name each type of dysmorphology illustrated by the separate examples below:
Amniotic band syndrome
Potter’s syndrome
Clubfoot
Amniotic band syndrome - disruption
Potter’s syndrome - sequence
Clubfoot - deformation
Name each type of dysmorphology illustrated by the separate examples below:
Fetal alcohol syndrome
Skeletal dysplastic syndromes
VACTERL syndrome
Fetal alcohol syndrome - dysplasia
Skeletal dysplastic syndromes - dysplasia
VACTERL syndrome - association
True/False.
Facial dysmorphological changes can often predict location changes and problems in the brain.
True
(“the face predicts the brain)
(e.g. a child with a midline cleft lip / palate might also have holoprosencephaly)
What are the two steps of clinical research that happen before human test subjects are involved?
Basis - lab work to establish potential therapy basis
Pre-clinical - synthesis, toxicology, formulation, regulatory
Phase I studies use a small group of healthy individuals to do what?
Phase II studies do what?
Establish safe dosage and schedule for new therapy;
establish biological effect, establish efficacy
Phase III studies do what?
Phase IV studies do what?
Compare new therapy to old therapy;
figure out where the new therapy can fit into the current market
In phase I trials, we say: “is it _________?”
In phase II trials, we say: “is it _________?”
In phase III trials, we say: “is it _________?”
In phase IV trials, we say: “is it _________?”
Safe
Efficacious
better than the existing therapy
market-ready
What four disorders comprise almost 70% of all skeletal dysplasias?
Achondroplasia,
thanatophoric dysplasia,
osteogenesis imperfecta,
achondrogenesis
What is the very severe skeletal dysplasia in which cartilage is not produced?
This condition is often lethal due to a narrow thorax and pulmonary hypoplasia.
Achondrogenesis
What disorder is characterized by a ‘clover-leaf’ skull, frontal bossing, midface hypoplasia, micromelia, macrocephaly, brachydactyly, and CNS abnormalities?
What is the inheritance pattern and associated gene?
Thanatophoric dysplasia
Autosomal dominant - FGFR3 gene
What is the most common cause of disproportionate short stature?
Achondroplasia
In what fairly common skeletal dysplasia is there sometimes craniocervical junction compression, increasing the risk of death in infancy?
Achondroplasia
In addition to achondroplasia, what other two disorders are linked to mutations in the FGFR3 gene?
Thanatophoric dysplasia,
hypochondroplasia
Name some of the signs associated with thanatophoric dysplasia.
‘Clover-leaf’ skull, frontal bossing, midface hypoplasia, micromelia, macrocephaly, brachydactyly, and CNS abnormalities
Which tends to be more severe in its skeletal features, achondroplasia or hypochondroplasia?
Which tends to show intellectual disability and/or epilepsy more often?
Achondroplasia;
hypochondroplasia
