[CIS PIDD] [CIS-PAGID] CVID Risk for children - further screening?

[Grimbacher, Bodo]

Dear all,

Am 04.06.12 11:52 schrieb "Stan Ress" unter <Stan.Ress at uct.ac.za>:


>How would it be best to monitor for future development of CVID in

>children who have affected parents, and is genetic screening actually

>warranted?

> 

>I have the following 3 scenarios:

> 

>1. A man contacted me about his 32 year-old wife who was diagnosed with

>CVID & is getting monthly IVIG. I have no further details but I doubt any

>genetic studies were done. He asked me about the risk for his 3 kids aged

>5 years, 3 years & 1 year & I indicated ~10%. Would one do periodic serum

>Ig levels, or only test in the event of recurrent URTI's ?


I would monitor the kids clinically and IF a blood test for other reasons
on the kids is needed also tick the IgG box :-)


> 

>2. I have 2 sisters diagnosed with CVID on IVIG therapy. Raising the

>question of further screening of the family, I was told they are all

>totally against this.


Two sisters with healthy parents may indicate towards a recessive form of
CVID, so the chance of inheritance (provided an unrelated partner) is so
small that I would agree with this family and NOT pursue and screening of
offspring.
Having said this, these forms of CVID have in recent years been most
informative on the elucidation of what is genetically going on in CVID;
with ICOS deficiency and CD19 deficiency all diagnosed in families with
affected sib-pairs. So from the research perspective, we would be very
interested in these CVID families.


> 

>3. A related but distinct query. A young 16 year-old man with late onset

>XLA (undiagnosed) presented with severe chest infection and unfortunately

>died, despite AB therapy. He had absent B-cells on FCM, very low IG

>levels, absent plasma cells on post-mortem, & confirmed gene mutation: G

>to A transition at cDNA position 1574 (c, 1574G>A) in exon 16 of the BTK

>gene.

> 

>He has a younger brother. In this case, simply measuring circulating

>B-cells & Ig levels in the sib should be adequate? Full genetic

>screening, while of academic interest, is not affordable by this family,

>& not offered by the state's public health care system.


Getting the brothers B cells and IgG serum levels should be sufficient.
However, as you know the brother's mutation, you will need only one PCR
and one sequencing reaction to confirm or rule-out this family's mutation.
This should cost around 50 EUR (at least it does in EuropeŠ)

Best, Bodo

Prof. B. Grimbacher

Scientific Director
CCI - Centre of Chronic Immunodeficiency
UNIVERSITY HOSPITAL FREIBURG
Germany


> 

>I would value any advise in these situations.

> 

>Thanks & Regards,

> 

>Stan Ress

>

>

> 

>--

>Stanley Ress

>Associate Professor of Medicine

>Head: Division of Clinical Immunology

>Department of Medicine

>H47 Old Main Building-room 26

>Groote Schuur Hospital and UCT

>Observatory 7925

>Cape Town

>South Africa

>TEL:INTERN. + 2721-4066201 or 4066197

>FAX:   "    + 2721-4486815

>Cell: 0833115482 

>email: stan.ress at uct.ac.za

>>>> "Church, Joseph" <JChurch at chla.usc.edu> 2012/05/07 04:59 PM >>>

>Thank you, Charlotte.  JC

>

>-----Original Message-----

>From: pagid-bounces at list.clinimmsoc.org

>[mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of

>Cunningham-Rundles, Charlotte

>Sent: Monday, May 07, 2012 7:35 AM

>To: PAGID

>Subject: Re: [CIS-PAGID] CVID Risk for children

>

>I agree with Mary Ellen.

>

>>From our data,

>

>I use the figure 8% overall for immune deficiency but of those only 2% of

>the group have CVID in any other member, the rest were IgA deficient.

>

>Note the older literature that also says that the female is more likely

>(4x I think) to pass this on than the male with CVID.  Not something I

>can address from our data, as we have more sibs with unaffected parents

>than any other combination.

>

>As for TACI, the 50% rule does not really work as the majority have non

>immune deficient family members ( one parent and sometimes a sib or

>child) with the same mutation.

>

>

>Charlotte Cunningham-Rundles, MD, PhD

>Departments of Medicine and Pediatrics

>The David S Gottesman Professor

>The Immunology Institute

>Mount Sinai School of Medicine

>1425 Madison Avenue

>New York, NY 10029

>Phone: 212 659 9268

>Fax: 212 987 5593

>Email: Charlotte.Cunningham-Rundles at mssm.edu

>

>

>

>

>> From: "Church, Joseph" <JChurch at chla.usc.edu>

>> Reply-To: PAGID <pagid at list.clinimmsoc.org>

>> Date: Mon, 7 May 2012 14:16:35 +0000

>> To: PAGID <pagid at list.clinimmsoc.org>

>> Subject: Re: [CIS-PAGID] CVID Risk for children

>> 

>> I thank you all for the very useful information.  JC

>> 

>> -----Original Message-----

>> From: pagid-bounces at list.clinimmsoc.org

>> [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Conley, Mary

>> Ellen

>> Sent: Monday, May 07, 2012 7:11 AM

>> To: pagid at list.clinimmsoc.org

>> Subject: Re: [CIS-PAGID] CVID Risk for children

>> 

>> I use the same figure as Bodo - 10% but I come at it from a slightly

>> different perspective.  Like Bodo, I consider the percentage of

>> patients with CVID who have affected family members.  But some of that

>> 10% is not really CVID - it may be IgA deficiency or abnormal serum

>> immunoglobulins that are detected because of family studies rather

>> than repeated or unusual infections.  It may be autoimmune disease.  I

>> also have a gut feeling, but no data, that with the sickest patients,

>>the risk may be a little higher.

>> 

>> Mary Ellen Conley, MD

>> West Research Tower

>> LeBonheur Children's Hospital

>> 50 N. Dunlap St.

>> Memphis TN  38103-2800

>> Tel     901-287-4657

>> FAX  901-287-4551

>> mconley at uthsc.edu<mailto:mconley at uthsc.edu>

>> 

>> -----Original Message-----

>> From: pagid-bounces at list.clinimmsoc.org

>> [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Grimbacher,

>> Bodo

>> Sent: Saturday, May 05, 2012 4:34 PM

>> To: pagid at list.clinimmsoc.org

>> Subject: Re: [CIS-PAGID] CVID Risk for children

>> 

>> I tell my patients 10%.

>> Why?

>> A maximum of 10-20% of CVID patients are familial (10% in AD families,

>> and suspected additional 10% with new mutations).

>> So assuming 20% of CVID patients have a Mendelian form of CVID, and

>> most of them seem to be autosomal-dominant, I In AD traits the risk of

>> any offspring is 50%.

>> therefore arrive at an overall risk of 10% for an offspring of newly

>> diagnosed CVID patients.

>> Yours,

>> Bodo Grimbacher

>> CCI- Centre of Chronic Immunodeficiency Freiburg, GERMANY

>> 

>> 

>> Am 05.05.12 01:27 schrieb "Church, Joseph" unter <JChurch at chla.usc.edu>:

>> 

>>> Colleagues:

>>> 

>>> I just consulted on a 34yo man with probable CVID.  He and his wife

>>> have no other medical issues.

>>> 

>>> They asked "what is the liklihood that their children (yet to be

>>> conceived) will develop CVID?".

>>> 

>>> I would appreciate any insight (?data) you may have.

>>> 

>>> Thank you.

>>> 

>>> Joe Church

>>> Children's Hospital Los Angeles

>>> 

>>> 

>>> 

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