Balanced Translocations

Karuna SapruArshad Siddiqui

Janet SmillieAlison Teo

The case of Mr and Mrs Snow and their Christmas Baby Wish

Dear Dr Claus,

I would be very grateful if you could see Mr and Mrs Snow in your clinic who have been trying for a baby for some time now. Unfortunately, Mrs Snow has suffered three first trimester miscarriages and the couple are finding it hard to come to terms with this. There is a positive family history on the paternal side with Mr Snow’s mother suffering from two miscarriages. His sister is also in very early pregnancy and may also therefore benefit from cytochromal genetic analysis and a referral to your clinic.

I have arranged for lupus anticoagulant and anticardiolipin antibody studies and a cytogenetic chromosomal analysis for each partner and the results should now be available to you. On further discussing the situation with the couple I have mentioned the possibility of a genetic cause for their recurrent miscarriages with this being the reason for their referral to your clinic for further information.  

I hope you are able to help this couple.Yours sincerely,

  Dr. S. Leigh

History• Personal • Family History

– Affected and at risk relatives– Automimmune disease

Why does miscarriage happen? – Uterine abnormalities– Immunologic reasons– Medical (thyroid, DM)– PCOS– Infection– Lifestyle– Genetics

• Commonest – trisomy 16

Pedigree

?

Genes are found in paired

chromsomes

Each parent has 23 chromosome pairs and a pair of sex chromosomes

Each parent passes on one chromosome from each

pair to their offspring

Normal DeletionBalanced Deletion

Mrs Snow Mr Snow

Balanced

• Same as Mr Snow• Risk Multiple Myeloma

Deletion of chromosome 4p

Wolf-Hirschhorn Syndrome Mental retardation

Cleft lip/palate - feeding difficulties

Microcephaly and seizures

Poor muscle tone

Characteristic facies-hypertelorism-down turned mouth-small chin

WHSC1 geneWHSC1 gene

Deletion of chromosome 14q

•Few described cases

•Overlapping toes

•Pointed chin

•Congenital heart anomaly

•Excess neck skin

•High vaulted palate

•Narrow palate

•Small jaw

•Developmental delay

•Seizures

Options

• Genetic Ix• Preimplantation genetic Dx• CVS• amniocentesis

Different Situations

• Spontaneous mutation or inherited?

• If unbalanced translocation

• Sister– Test for translocation

Merry Christmas