[PAGID] Seeking help with what appears to be an autosomal dominant inflammatory disorder

[Kathleen E. Sullivan]

Please see some resources below.  I have heard Polly Ferguson speak  
and I know her work is moving quite quickly.  Although Majeed  
syndrome is AR, you could certainly envision other mutations of the  
same gene or associated proteins which could be AD.




The syndrome of chronic recurrent multifocal osteomyelitis and  
congenital dyserythropoietic anaemia. Report of a new family and a  
review
Auteur(s) / Author(s)
MAJEED Hasan A. (1) ; AL-TARAWNA Mosleh (2) ; EL-SHANTI Hatem (3) ;  
KAMEL Basem (4) ; AL-KHALAILEH Fatma (2) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Department of Paediatrics, University of Jordan, Amman, JORDANIE
(2) Division of Haematology, Department of Pathology, University of  
Jordan, Amman, JORDANIE
(3) Department of Pediatrics, Jordan University of Science and  
Technology, Irbid, JORDANIE
(4) Al-Basheer Hospital, Ministry of Public Health, Amman, JORDANIE
Résumé / Abstract
A new autosomal recessive syndrome of chronic recurrent multifocal  
osteomyelitis (CRMO) and congenital dyserythropoietic anaemia (CDA)  
with microcytosis has recently been described in four children (two  
sibships) of one consangineous Arab family. In this report, we  
describe the clinical features and course of the syndrome of CRMO and  
CDA in two additional patients (one sibship) from another  
consanguineous Arab family and review the literature. The two  
patients (brother and sister), the products of a consanguineous  
marriage, developed the syndrome at an early age of 3 weeks and 2  
months respectively. The diagnosis of CRMO was confirmed by  
radiological and technetium isotope bone scans. Bone marrow studies  
confirmed the diagnosis of CDA. Peripheral blood films showed  
hypochromia and microcytosis. The sites involved by CRMO were  
periarticular, mainly around the elbow, knee, wrist and small joints  
of the hand. The brother is now 21 years old and the sister 3.5 years  
old and CRMO is still active with frequent relapses. The brother  
developed flexion deformities at the age of 13 years. Both patients  
failed to thrive; weight and height were below the 5th percentile.  
Conclusion: this is the second report of the syndrome of chronic  
recurrent multifocal osteomyelitis and microcytic congenital  
dyserythropoietic anaemia, confirming it as a clinical entity,  
inherited as an autosomal recessive trait. The disease is  
characterised by an early onset, long clinical course of remissions  
and relapses, and seems to be different from the sporadic form of  
chronic recurrent multifocal osteomyelitis.
Revue / Journal Title
European journal of pediatrics   ISSN 0340-6199   CODEN EJPEDT

Polly Ferguson, MD
Research Profile

Division: Hematology/Oncology & Rheumatology
Pediatric Subspecialty: Rheumatology

Contact Information:
Office Tel: (319) 356-1608
Fax: (319) 356-7659
E-mail: polly-ferguson at uiowa.edu
Education and Training:

Predoctoral and Doctoral Education
BS, 1986, University of Iowa, Iowa City, Iowa
MD, 1990, University of Iowa, Iowa City, Iowa

Postgraduate Medical Education
Pediatric Intern, 1990-1991, University of Virginia, Charlottesville,  
Virginia
Pediatric Resident, 1991-1993, University of Virginia,  
Charlottesville, Virginia




Pediatric Immunology & Rheumatology Fellow, 1993-1997, University of  
Virginia, Charlottesville, Virginia
Post-Doctoral Research Fellow, 1997-1999, University of Virginia,  
Charlottesville, Virginia
Research Associate in Microbiology Pediatric Fellow, 1999-2000,  
University of Virginia, Charlottesville, Virginia
Research Interests

Chronic Recurrent Multifocal Osteomyelitis (CRMO)
CRMO is a chronic inflammatory disease of unknown etiology. It  
primarily affects children and results in recurrent fever and the  
development of multiple inflammatory bone lesions. It is frequently  
seen in association with other, more common, inflammatory disorders  
such as psoriasis, inflammatory bowel disease and cutaneous  
pustulosis making it a particularly interesting disorder to study.  
There are reports of affected siblings in the literature and  
published evidence for a susceptibility locus for CRMO on human  
chromosome 18q suggesting a genetic component to its etiology. In  
addition, there is a syndromic, autosomal recessive disorder, called  
Majeed syndrome, in which CRMO is a major clinical feature. The  
genetic basis of CRMO is further supported by the existence of a  
similar disorder in the mouse (cmo, chronic multifocal osteomyelitis)  
resulting from a spontaneous mutation that is inherited as an  
autosomal recessive trait. In collaboration with Dr. Hatem El-Shanti  
in the Division of Medical Genetics, we are in the process of  
dissecting the genetic basis of CRMO utilizing all 3 available  
models. First, the El-Shanti lab has recently demonstrated that  
Majeed Syndrome, a syndromic form of CRMO, is caused by defects in  
the LPIN2 gene. Second, my laboratory has recently identified the  
gene defect in the cmo mouse and are currently performing experiments  
to determine the immunologic abnormalities in these mice. Third, we  
(El-Shanti and Ferguson) are collecting DNA from patients with  
sporadic (non-syndromic) CRMO to see if we can determine the gene  
defect(s) in these patients. The goal of this research is to  
understand the genetic basis of chronic, non-infectious  
osteomyelitis. Knowledge about the gene defect(s) present in CRMO may  
aid in the understanding of the pathways of inflammation involved,  
not only in CRMO, but also in the inflammatory disorders that  
frequently accompany this disorder such as psoriasis and inflammatory  
bowel disease.

Kathleen E. Sullivan MD PhD
Chief, Division of Allergy and Immunology
Professor of Pediatrics
The Children's Hospital of Philadelphia
(p) 215-590-1697
(f) 267-426-0363


On Sep 3, 2008, at 8:44 PM, John Ziegler wrote:


> -

>

> Dear Colleagues

>

> We have a 15 month old girl who has two episodes of osteomyelitis,  

> effecting

> humerus and radius/ulna.  Both episodes appeared to start in the  

> adjacent

> joint (elbow and wrist) where there was a purulent effusion, before

> spreading to involve bone, were refractory to antibiotics, no  

> organisms were

> isolated despite multiple attempts, histopathology showed only a minor

> plasma cell infiltrate on later samples and immunodeficiency screen  

> was

> negative.  Inflammatory markers (ESR/ CRP) were moderately elevated  

> during

> the course of the disease.  She seemed to improve markedly with  

> NSAIDs.

>

> Her mother also suffered 5-6 documented episodes of osteomyelitis  

> (often at

> a site near to a joint) with moderately raised inflammatory  

> markers, and

> multiple episodes of what was thought to be septic arthritis with  

> pus in the

> joint, but again with no organisms identified and negative  

> immunodeficiency

> screen. She had occasional other infections including one buttock  

> abscess,

> an episode of pneumonia and several UTI's.  She has gone on to have a

> seronegative arthritis in adult life with difficult scarring acne  

> of onset

> in mid 30's.

>

> We wondered whether this is on the CRMO/SAPHO spectrum, but could find

> little evidence for the existence of such an early onset autosomal  

> dominant

> phenomenon.

>

> A/Prof. John B. Ziegler and Dr Paul Gray

> School of Women's & Children's Health, University of NSW

> C/o Department of Immunology & Infectious Diseases

> Sydney Children's Hospital

> High St., Randwick NSW 2031

> Australia

> T: (02) 93821515

> F: + 61 + 2 93821580

> E: j.ziegler at unsw.edu.au

>

>


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