1. MED CPC Case 4
Nicholas Vidor, Brock Urie, Anne Sirany, Abby Thyen, Sandi Riggs, Chris Steevens, Mark Vukonich, Jacob Ziegler

2. Complaint: “What is wrong with my babies?”
33 y.o. woman brings in her twin babies
Vaginally delivered at 38 weeks
Apgar scores of 9 for both
Both small birth size [wt.~ 3 lbs. 16oz and 4 lbs 4 oz] [Length~ 17.5 in. and 16.9 in.]
Normal head circumference [~12.2 in. for both]
Now twins are 25 months old

3. Physical Exam of Twins Short palpebral fissures
Normal linear growth and head circumference (25th percentile)
No significant cognitive delays
One twin had shortened forearms bilaterally, no evidence of a constriction mark, two rudimentary fingers without nails on each forearm.
Other twin had a cleft soft palate (has been surgically repaired)

4. Mother’s history 31 y.o. when gave birth to twins
Had normal full term delivery 13 years ago with different partner
Her mother died of AIDS
She is a single parent working as a medical assistant

5. Mother’s drug use
Had one week ‘alcohol binge’ during time of conception
Problems with morning sickness, took unknown drug given by her mother for 1-2 weeks
Used crack cocaine, alcohol, and marijuana at beginning of pregnancy
Went to chemical rehab, put on antabuse until discovered she was pregnant (~1 month)
Has not taken any more drugs

6. Important Developmental Periods

7. Contribute Now

8. Our List Congenital Abnormalities Viral – HIV, CMV
Substance Abuse - Teratogenic
Crack cocaine
EtOH – FAS
cigarettes
Antabuse
Mysterious Drug

9. Genetics Velo-cardio-Facial Syndrome (VCFS) Williams Syndrome
Most common syndrome associated with cleft palate.
Multiple anomalies including cleft palate, heart malformations, facial characteristics, and learning disabilities.
Chromosome 22q11 deletion.
Williams Syndrome
Characterized by distinctive “elfin” facial appearance and low nasal bridge.
Deletion of elastin gene, 7q.
De Lange Syndrome
1/3 born prematurely with facial disturbances that are present at birth and change little with age.
NIPBL gene mutations on chromosome 5p13.

10. Genetics Velo-cardio-Facial Syndrome (VCFS) Williams Syndrome
Most common syndrome associated with cleft palate.
Multiple anomalies including cleft palate, heart malformations, facial characteristics, and learning disabilities.
Chromosome 22q11 deletion
Williams Syndrome
Characterized by distinctive “elfin” facial appearance and low nasal bridge.
Deletion of elastin gene, 7q

11. Genetics
Karyotyping
Both twin were genetically normal

12. Genetics Supportive Evidence Contradicting Evidence
Twin A and B both have short palbebral fissures.
Twin B has a soft palate that was surgically repaired.
Twin A shortened arm
Contradicting Evidence
Karyotype was normal for both twins.

13. Key Developmental Periods WEEK 1 2 3 4 5 6 7 8 9 Conception
Treatment
03/12
Mysterious Drug? Given By Mother
Cigarettes
Crack Cocaine, Marijuana, EtOH
Antabuse
04/02
EtOH Binge
Drug Free
WEEK 1 2 3 4 5 6 7 8 9
Key Developmental
Periods
Amelia/
Meromelia
Upper
Limb
Cleft
Palate
Palate
-16wk
Highly Sensitive Period
Less Sensitive Period

14. Cocaine Exposure Small for gestational age Prematurity Microcephaly
Urogenital abnormalities
Neuro-behavioral disturbances
Cleft palate

15. Cocaine Exposure Evidence for: Evidence against: Cleft palate
Slightly premature
Small for gestational age
Evidence against:
No cognitive findings
Doesn’t explain other physical findings
Time of exposure: wks 1-2 (cleft palate= wks 7-8)

16. Alcohol Exposure -Fetal Alcohol Spectrum Disorders (FAS)
-Small for gestational age
-Mental retardation
-Microcephaly
-Ocular abnormalities
-Short palpebral fissures
-Joint abnormalities

17. Fetal Alcohol Syndrome
Four basic findings:
growth deficiency
characteristic FAS facial phenotype
CNS damage/dysfunction
alcohol exposure in utero

18. Alcohol Exposure Evidence for:
Short palpebral fissures
Premature
Time frame (around wk 8)
-falls within upper limb and cleft palate development
Mom’s alcohol binge
Evidence against:
No mental retardation
Doesn’t explain degree of arm abnormalities
No delayed growth
Normal head circumferences

19. Antabuse (Disulfiram)
Therapy Started : April 2nd 2000
Therapy Stopped: After 1 month use ~ May 2nd 2000.
Embryonic Upper limb development: weeks 4-9
Disulfiram exposure during this critical time of limb bud development!

20. Effects of Disulfiram on Upper Limb Development
Disulfiram inhibits acetylaldehye dehydrogenase – preventing alcohol oxidation
Increased blood levels of acetylaldehye
Animal studies have shown:
Disulfiram intoxication associated with “tibial dyschondroplasia” and growth plate necrosis
Decreased DNA synthesis in mouse embryos exposed to Disulfiram

21. Effects of Disulfiram on Upper Limb Development
Limb abnormalities described in infants of women treated with Disulfiram during pregnancy:
Club feet
Radial aplasia
Phocomelia: very short or absent limb long bones, fused fingers

22. Disulfiram’s Effect on this Pregnancy
Therefore Disulfiram exposure during upper limb development may have contributed to Twin A’s upper limb abnormalities!!!!

23. Mysterious Drug? Given By Mother
Conception
03/04 ± 7 d
Treatment
03/12
Mysterious Drug? Given By Mother
Cigarettes
Crack Cocaine, Marijuana, EtOH
Antabuse
04/02
EtOH Binge
Drug Free

24. Question #1
All of the following are developmental malformations characteristic of cocaine exposure in the first trimester except:
Microcephaly
Cleft palate
Urogenital malformations
Hemi-penis
Neuro-behavioral disturbaces

25. Question Deuce
The most critical risk of limb deformations is what period following gestation?
Days 14-20
Days 3-11
Days 28-35
Days 21-27

26. Question drei
Which of the following drug abuse treatment tools are associated with absent limb long bones?
Nicotine
Antabuse (disulfiram)
Methadone (dolophine)
Buprenorphine (buprenex)