Dysmorphology! Flashcards
What is Dysmorphology
•External defects
- Club foot
- Six (or more) digits (Polydactyly)
•‘Internal’ defects
- TOF
- Coarct Aorta (usually detected later in life)
What is Coarctation of the Aorta? Coarctation of the aorta is a birth defect in which a part of the aorta is narrower than usual. If the narrowing is severe enough and if it is not diagnosed, the baby may have serious problems and may need surgery or other procedures soon after birth.
Why ‘Dysmorphology’ is important?
•To make a specific diagnosis – if possible
- Phenotypic features
- Investigations – Imaging
- Karyotype / genetic analysis
•Specific diagnosis – can lead to specific treatment
- Counsel parents
- Estimate recurrence risk
- Prenatal diagnosis (& intervention) – where possible
How to classify Dysmorphology?
- Single Defects
- Multiple Defects
oNon-Random Grouping (Associations)
Single Defects
•Defect involves just a single structure
- Child otherwise “Normal”
- Examples - Congenital diaphragmatic hernia (CDH) , congenital talipes equinovarus (CTEV)/club foot, or talipes equinovarus (TEV) Cleft lip/palate, CHPS, cardiac septal defects, neural tube defects
- Multi-factorial (?unknown). Most times we don’t know what is the underlying cause of these problems but sometimes we do know. i.e with neural tube defect, we know that folic acid deficiency can be responsible.
- Recurrence risk: 2 to 6%
Single Defects
•Defined by the nature or evolution of the abnormality
1 •Malformation; A Localised defect in differentiation of that organ. i.e CHPS, Cardiac septal defects
2•Deformation
3•Disruption
Pyloric Stenosis
- 3 per 1000 live births
- Common in Males first born 4:1
• Non-bilious projectile vomiting - 2nd week
- Pyloric ‘ tumour’ after a test feed. the tumour is not malignant cancer, it’s just swelling.
- Hypochloremic (hypokalemic) metabolic alkalosis- Due to a loss of potassium
•Pyloromyotomy is the diagnosing procedure where they make a little nip in the pyloric muscle and they do an incomplete division of the pyloric muscle so that it becomes open.
- They have a visible peristalsis of the stomach where the stomach is trying to push food from the stomach to the duodenum and its being obstructed by the stenosis.
- The pyloric muscle is very thick and if its more than 4mm in thickness , then it confirm a pyloric stenosis.
Deformation in single defect conditions
- There is Structural alteration after ‘normal’ differentiation
- example Congenital diaphragmatic hernia (CDH) , congenital talipes equinovarus (CTEV)/ Clubfoot.
Dysplastic Hip
• Can be a completely dislocated, dislocatablehip
- Common in Female 9:1, 1 in 1000 / 100
- It is common in babies born in Breech because the babies often have longer let’s leading to hip hyperextension making it easier to dislocate the hip joint.
•Asymmetric skin folds
You the following test to do a physical assessment in babies
1• Barlow test – to dislocate
2• Ortolani test – to relocate the displaced hip. when the relocation happens, you get s distinct Clunk vs Click.
- Early Detection– Conservative treatment (Pavlik Harness).The earlier the diagnosis, the easier the treatment.
- Late Detection– Surgical correction
•Disruption in Single Defects
- Structural destruction of a previously ‘normally’ formed part
- Often Entanglement, disruption of blood supply
Intestinal Atresias
•Oesophageal atresia (with/out (TO) tracheoesophageal fistula)
•Duodenal atresia
•Jejunal / Ileal atresia
o(incomplete – stenosis)
- Polyhydramnios
- Intestinal obstruction
- Emergency!
Atresia is the absence or closure of a natural passage of the body. .
Sequence
-Although we may have some single defects, sometimes, multiple anomalies can Happen following a single defect which is known as a cascade of secondary and tertiary errors in differentiation.
•Examples
- Breech deformation sequence
- Amniotic band disruption sequence
- Breech is not an abnormality but because of the position of the fetus, it can lead to a series of events which is called a sequence.
Multiple Defects
•Several structural defects (at least 2 systems)
•All defects have a single known or presumed cause
- Chromosomal abnormalities
- Single gene mutations
- Teratogens
•Recurrence risk – 0 to 100% !!!
Chromosomal abnormalities
•Abnormalities of Chromosomal number
-Trisomy – 21 (Downs Syndrome), 18 (Edwards syndrome), 13 (Patau syndrome).
-Monosomy – Mostly lethal; (Turner Syndrome)
-Monosomy is the state of having a single copy of a chromosome pair instead of the usual two copies found in diploid cells.
•Abnormalities of chromosomal structure
oDeletions, micro-deletions – 4p-, 5p- etc
•Sex chromosome abnormalities
-45XO (Turners Syndrome), 47XXY (Klinefelter), 47XYY (Multiple Y syndrome)
- Mosaicism
- Fragile sites / Breakage syndromes
- Imprinting / Uniparental disomy
-Monosomy is not compatible with life and most of the monosomies are lethal except Turners syndrome which is monosomy X where you have 1 X chromosome.
Down Syndrome
•1 in 660
•Trisomy 21 (translocation)
- Typical facies
- Clinodactyly, Simian crease
- Congenital Heart Defects
- Duodenal atresia
- Hypotonia
- Delayed Development
- Good Social skills
-In a translocation, a segment from one chromosome is transferred to a nonhomologous chromosome or to a new site on the same chromosome. Translocations place genes in new linkage relationships and generate chromosomes without normal pairing partners.
Single gene mutations
•Mutations or ‘pathologic’ variants
•Mendelian inheritance patterns
- Autosomal Dominant - Marfans
- Autosomal Recessive - PKU (Phenylketonuria)
- X-linked Recessive - Haemophilia
- X-linked Dominant – Hypo Phosphataemic Rickets
- Maternal Inheritance – Mitochondrial diseases
•(Extended) Family history helpful
•These mutations can be a Fresh or De Novo mutation in that family.
Neurofibromatosis type 1
•1 in 4000; AD, 17q11.2
- Variable penetration
•Neural crest cells – differentiation / migration problem.
•The signs are; Café-au-lait spots, neurofibromas, freckling, lisch nodules, bone lesions, optic glioma, FH of NF1.
- Non cancerous CNS tumors
- Disfiguring & varied features
- Health surveillance
Teratogens
-Teratogenic defects are caused by exposure to chemicals or infectious agents during pregnancy.
1•Infections like Congenital Rubella that causes deafness, cataract/blindness , developmental delay.
2•Chemicals
- Alcohol exposure can cause Foetal alcohol syndrome
- Maternal PKU (Phenylketonuria)
3. Drugs
- Thalidomide
- Antiepileptic drug (Valporate)
