1. Genetics in LEND
Kory Keller, M.S., C.G.C.

2. Outline Introduction Single discipline Genetics Clinic
Genetics in multidisciplinary settings
Pedigrees
Case presentations

3. Introduction What is genetic counseling?
Who should be offered genetic counseling?
Cute kids
Visit to genetics clinic

4. What is genetic counseling?
Genetic counseling is a communication process intended to help families to:
Comprehend the medical facts
Understand the contributions of genetics to the disorder and its recurrence risks
Understand the options available for dealing with this risk
Choose the best course of action most compatible with their family goals, values, and religious beliefs
Make the best possible adjustment to the condition and its implications

5. Who should be offered genetic counseling?

6. Who should be offered genetic counseling?
Individuals or families with:
A suspected or known genetic disorder
Birth defects, growth disorders, metabolic disorders, neurologic disorders
Intellectual disability of unknown etiology
Dysmorphic features
Infertility, pregnancy loss
Consanguinity
Early onset cancer
Concerns about recurrence of intellectual disability, birth defects, cancer, or a genetic disorder in the family

7. Kids with common genetic conditions

8. A visit to Genetics Clinic

9. Genetics clinic visit Information gathering Establishing diagnosis
Genetic counselor assesses the family’s major questions and concerns
She then obtains the pedigree
She, a trainee and/or geneticist obtain the pregnancy, medical, and developmental histories
Establishing diagnosis
The geneticist and trainee perform a physical examination (if indicated)

10. Genetics clinic visit
We meet in the conference room as a team and make a diagnosis or decide on a work-up

11. Genetics clinic visit Establish a diagnosis Risk assessment
Based on exam, if a clinical diagnosis clear
Otherwise discuss testing
Risk assessment
Information giving
Psychosocial support

12. Genetics in multidisciplinary clinics
Muscular dystrophy association clinic
Skeletal dysplasia clinic
Marfan clinic
Craniofacial clinic

13. Shriner’s Hospital Clinics
Neuromuscular
Skeletal dysplasia

14. Genetics role Help clarify diagnosis
Provide information about potential therapies, new research
Review genetic counseling
Provide information to distribute to at risk family members about testing
Support families
Provided readable information to families

15. Example - research
typical
usually BMD
usually DMD
?BMD

16. Example – family information

17. Heart of genetic counseling
What families really want to know
How we can best support families

18. Pediatric genetics visits most important issues to discuss
What is wrong
Available medical treatment/management
Can the condition be cured
Coping skills
Chance of condition occurring in family
Smith, Genetic Counseling, Wiley & Liss, 1998.

19. Support – Helping the family cope
Recognize and discuss the emotional responses of family members to information given.
Review normal grief responses and signs that might indicate the need for further psychosocial support.
Listen to the whole story, and hear what this situation has meant to the family.
Explore strategies for communicating information to others.
Provide written materials and referrals to support groups, other families with the same or similar condition, and local and national service agencies.

20. Pedigrees

22. Pedigree symbols 3 P Male, female, unknown 3 affected males
Women who died at 35
Pregnancy, spontaneous abortion, termination of an affected pregnancy, stillbirth at 28 wk 3
d. 35
Draw a pedigree P
SB 28 wk
J. Genet. Counsel. 17:424, 2008

23. Sample complicated pedigree

24. Case presentations

25. Case presentation 4 yo boy with “congenital CMV”
Pregnancy – IUGR, 2 vessel cord, 36 weeks
Medical - laryngomalacia, atrial septal defect, febrile seizures, “normal 46, XY” karyotype
Development – walked 2 ½, a few signs but no words, not toilet trained
Mother pregnant (since she was told it was not genetic) with another male fetus who has “exactly the same issues”
Mother called because she’s currently pregnancy and the fetus is showing all the features her previous child with “congenital CMV” had prenatally
Induced delivery due to IUGR
Medically developed febrile seizures at 20 months, ?1 non-febrile seizure, placed on meds for awhile, after sz-free for 1 yr taken off meds (at 3 ½)
Slow, steady development, 5 yr doing well, knows some of ABS, 1-20, learning to write Jack (Jack Hanna)
Chromosomes “normal 46, XY” at 500 bands at Genzyme
Before following the case congenital CMV info

26. Congenital CMV Microcephaly, IUGR Hepatosplenomegaly
Petechiae, jaundice
Hearing loss, chorioretinitis
Intracranial calcifications, brain atrophy
Seizures

28. Examination Ht <3%, wt <3%, HC <<3% Dysmorphic
Epicanthal folds
Malar hypoplasia
Prominent nasal tip, long columella, short philtrum
Micrognathia
Bilateral pes planus
Toe nail hypoplasia
Not CMV, ordered CMA
Small and cute but dysmorphic
Not reminescent of any particular genetic condition

29. Detect about 5-10 Mb i.e. 5-10 million base pairs,

30. Detects extra of missing of about 500 kb or 500,000 kb, a 100x increase in resolution

32. arr 4p16.3-p16.1 x1,12q24.32-q24.33 x3

33. Wolf-Hirschorn syndrome
Dysmorphic features
IUGR, GR, microcephaly
Hypotonia, seizures, brain anomalies, feeding problems
Skeletal anomalies
CHD HL
ID/MR

34. Father’s karyotype
Translocation 4;12
Normal 12
Normal 4

35. t(4p;12q) 4p -;12q+ 4p -;12q+ Pulmonary stenosis Brother died of PAS
Similar case several months later
Moving on to another clinic day when we saw two different families one with a del and one with a dup of the same chromosomal region in back-to-back time slots
t(4p;12q)
4p -;12q+
4p -;12q+
Pulmonary stenosis

36. What clues said it wasn’t an infection?

37. What clues said it wasn’t a prenatal infection?
Boy had unusual growth, a congenital heart defect, and developmental issues
Another child was affected
There was a suspicious more distant family history

38. Cleft palate Healthy 6 mo girl with history of Pierre-Robin sequence
Recently diagnosed with myopia
Mom has severe myopia, retinal detachment, and early osteoarthritis

39. Cleft Lip and/or Palate
Cleft lip +/- palate
1/1000 births
More common in males
More common in Asians, American Indians
Cleft palate
1/2000 births
More common in females

40. Syndromes associated with clefting
Trisomy 13
EEC syndrome
Van der Woude syndrome

41. Isolated cleft palate or syndromic cleft palate?
Otherwise healthy babe
Typical facial appearance
Normal development
Multifactorial
RR 2-5%
May be associated medical problems
May be dysmorphic features
May be DD/ID
Usually AR, AD, or XR
RR up to 50%

42. Stickler syndrome

43. Stickler syndrome key features
Ocular - cataract, myopia, vitreous anomaly, retinal detachment
Craniofacial - midface hypoplasia, bifid uvula, cleft palate, micrognathia, Pierre-Robin sequence
Audiologic – sensorineural hearing loss
Joint – hypermobility, mild skeletal dysplasia, early osteoarthritis

44. What clues said it wasn’t an isolated cleft?

45. What clues said it wasn’t an isolated cleft?
Pattern of health issues
Similarly affected mother

46. Summary

47. Key points Genetics helps multidisciplinary teams
New technology can lead to new diagnoses and therapies
Family history is important (and cheap)
Genetics is by far the most interesting specialty

48. Where to go for help Local resources Websites
University genetics departments
Local genetic counselors
Websites