Developmental disorders and syndromology Flashcards
What is dysmorphology?
The study of congenital anomalies and unusual physical features.
What is a syndrome?
A set of developmental anomalies “running together” in a consistent pattern. (Or a condition characterized by a set of associated symptoms.)
Name some forms of developmental disorders.
Learning difficulties. Autism spectrum disorders. Schizophrenia. Congenital malformation. Delay development/growth. Behavioral problems. Dysmorphology. Intellectual disabilities. Epilepsy.
What is a malformation sequence?
A sequence that occurs when a primary anomaly itself determines additional defects.
What are the differences between malformations, deformations and disruptions?
Malformation is an intrinsic disruption (e.g. non-migrating neural crest) during the embryonic period. Deformation is an extrinsic disruption (teratogen) during the fetal period. Disruption is breakdown of a normal tissue. Neither malformation nor deformation are “normal” tissues.
What is dysplasia?
Dysplasia is an abnormal growth or development of cells (microscopic scale) and/or organs (macroscopic scale), and/or the abnormal histology or anatomical structure presumably resulting from such growth.
Name some general causes of congenital malformations/syndromes.
Mechanical (disruption, deformation).
Teratogenic exposure.
Maternal illness.
Infection.
Genomic variants (sequence variants, copy
number variants) (affecting genes critical
for morphogenesis).
List the five steps of a consultation about developmental disorders.
1) History.
2) Examination.
3) Genetic testing.
4) Further investigation.
5) Making a diagnosis.
What are important aspects of history during a consultation on developmental disorders.
Family history - “de novo” or hereditary mutation?
Pregnancy and birth.
Neonatal period.
Developmental milestones/performance in school.
Behavioral phenotype.
What are some dysmorphic traits in children with fetal alcohol syndrome?
Thin upper lip. Smooth philtrum. Epicanthal folds. Small eye opening. Small head circumference. Short nose.
What are important aspects of examination during a consultation on developmental disorders.
Observation.
Take photos or compare to photos.
Recognizable - Particular, rare malformations. “Gestalt” - most catching feature.
Use of growth charts, including OFC and proportions.
Facial measurements.
Major/minor abnormalities.
Reevaluate in a few years.
What are the main types of genetic abnormalities tested for when conducting a consultation on developmental disorders.
Amount of DNA (copy number). Standard G-band chromosome analysis, multiplex ligation-dependent probe amplification (MLPA), SNP-array.
Sequence of DNA. Sequencing of target genes, gene panels, the entire exome, or the entire genome.
What is a “de novo” mutation?
An alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell (egg or sperm) of one of the parents or in the fertilized egg itself.
Dominant “de novo” mutations are the most common cause of developmental disorders in children.
When conducting a consultation of developmental disorders, what might further investigations entail?
Metabolic screening.
X-rays or other medical imaging.
Other specialist examination.
Why is it important to make a diagnosis when dealing with a developmental disorder?
Prognosis. Monitoring and/or preventing symptoms. Risk of recurrence. Establishing contact with other families dealing with the same situation. Dealing with society in general. Treatment.
What genetic analysis in central when tailoring diagnostics and treatment based on biological variety in each individual?
Genome sequencing.
