Topic 5 Part 4 Child genetics

Question 1

Congenital heart disease (CHD)

Answer 1

1. 5-10% of cases are caused by single-gene or chromosomal mutations; 1-2% of cases are caused by environmental factors (teratogen exposure or infection).
2. Frequently found in association with other anomalies; higher risk if siblings also have CHD.
3. Common comorbidities: Down syndrome, Turner syndrome.

Question 2

Developmental dysplasia of the hip (DDH)

Answer 2

1. Congenital disorder in which the hip socket is not large enough to accommodate the head of the femur.
2. Caused by a shallow angled acetabulum, lax connective tissue (muscle, etc.), inborn errors of hormone metabolism.
3. Manifestations at birth: Extra skin folds on the inner thigh, positive Ortolani click, one leg shorter than the other.
4. Increased incidence among Lapps and Navajos.

Question 3

Neural tube defects (NTD) - spina bifida, myelomeningocele

Answer 3

1. Occurs primarily due to an environmental trigger which is a folic acid deficit in the maternal diet.
2. Manifestations: Induration in the lower thoracic-lumbar area, abnormal tuft of hair, hydrocephalus, etc.
3. Diagnosis: Ultrasound, elevated AFP level - however this has a high false positive rate.
4. Interventions: Child kept prone at all times, prepare for surgical closure and V-P shunt.

Question 4

Cleft lip and palate

Answer 4

1. A major anomaly - not life-threatening but has psychosocial effects, particularly speech.
2. Increased incidence in Native American, Scandinavian, and Japanese populations.
3. Associated with DiGeorge syndrome (cardiac component), Van der Woude Syndrome.

Question 5

Attention-deficit/hyperactivity disorder (ADHD)

Answer 5

1. Genetic factors account for 80% of the etiology of ADHD, possibly involving a dopamine deficit.
2. Also associated with a variety of prenatal, perinatal and postnatal factors.

Question 6

Fragile X syndrome

Answer 6

1. Occurs when the fragile X mental retardation protein, which is important for normal brain development, is missing.
2. Common features: Cognitive disability, autism spectrum disorders, avoidance of eye contact, sensory integration difficulties, hyperflexible small joints, large ears, hand flapping.
3. Significant comorbidity with ADHD.

Question 7

“Minor” anomaly

Answer 7

An unusual anatomic feature that is of no serious medical or cosmetic consequence to the patient. A minor anomaly of the feet might, for example, be curvature of the second toe so it overlaps the third toe a little.

Question 8

“Major” anomaly

Answer 8

Has serious consequences either physically and/or psychosocially. An example might be a cleft lip and palate, a birth defect of serious medical and cosmetic consequence to the child.

Question 9

Epigenetic inheritance

Answer 9

Occurs when a phenotype is inherited through means other than changes in DNA sequencing - DNA methylation causes the suppression of portions of genes.

Question 10

DiGeorge syndrome/VCFS (velocardial facial syndrome)

Answer 10

Manifests through palatal abnormalities (cleft lip and/or palate); conotruncal heart defects (e.g., tetralogy of Fallot, interrupted aortic arch, ventricular septal defects, vascular rings); facial abnormalities.

Question 11

Hypoplastic right heart - Epstein’s Anomaly

Answer 11

Involves tricuspid valve malformation, ventricular arrhythmias; Wolff-Parkinson-White syndrome has been diagnosed in 10-18% of patients, and can be seen on ultrasound.

Question 12

Holt-Oram Syndrome (HOS)

Answer 12

“Heart-hand syndrome”, an autosomal dominant disorder characterized by abnormalities of the upper limbs and heart, especially atrial septal defects and thumb (radial) abnormalities.

Question 13

Holt-Oram Syndrome is due to mutations on the _ gene.

Answer 13

TBX5 (which is important in the development of both the heart and upper limbs).

Question 14

Developmental dysplasia of the hip is associated with mutations on the _ gene.

Answer 14

VDR.

Question 15

Developmental dysplasia of the hip is treated through the use of _

Answer 15

Pavlik harnesses and spica casts.

Question 16

Van der Woude Syndrome

Answer 16

An autosomal dominant (50% chance with each pregnancy) alteration in a single gene on chromosome 1 with predominantly orofacial malformations. Seeking treatment early in the child’s life allows for timely surgery, speech therapy, and dental care.

Question 17

ADHD is associated with mutations on the _ gene.

Answer 17

LPHN3.

Question 18

Fragile X is associated with mutations on the _ gene.

Answer 18

FMR1 (due to methylation).

Question 19

Two genetic tests that can detect fragile X syndrome

Answer 19

1. Southern blot analysis - can detect methylation, inappropriately sized genes, and mosaicism (mixture of different cell types).
2. Polymerase chain reaction (PCR) - can determine the number of repeats on a gene.