[ARVD-FORUM] Pathological difficulties to distinguish lipomatosis from true ARVD. Dr Perez Riera

[ARVD Symposium]

English - Portuguese

Dear Prof Guy: 
Similarly  in the Carvajal Syndrome (Carvajal-Huerta L. Epidermolytic 
palmoplantar keratoderma with woolly hair and dilated cardiomyopathy. J Am 
Acad Dermatol. 1998; 39:418-421.) a familial, cardio-cutaneous, autosomal 
recessive entity, mapped to the short arm of chromosome 6 (6p24) and caused 
by a 7901delG mutation in exon 24 of desmoplakin. This is an intracellular 
protein that links desmosomal adhesion molecules to intermediate filaments of 
the cytoskeleton. It causes premature deletion of the codon located in the 
amino acid with number 18, causing truncation of the C-terminal domain in the 
region that interacts with intermediate filaments.

Desmosomes are major cell adhesion junctions, particularly prominent in the
epidermis and cardiac tissue and are important for the rigidity and strength
of the cells. The desmosome consists of several proteins, of which
desmoplakin is the most abundant. Norgett et al.described the first
recessive human mutation, 7901delG, in the desmoplakin gene which causes a
generalized striate keratoderma particularly affecting the palmoplantar
epidermis, woolly hair and a dilated left ventricular cardiomyopathy. There
are markedly decreased amounts of specific immunoreactive signal for
desmoplakin, plakoglobin and the gap junction protein, connexin 43, at
intercalated disks. The intermediate filament protein, desmin, which is
known to bind desmoplakin, showed a normal intracellular pattern of
distribution but failed to localize at intercalated disks (Kaplan SR, Gard
JJ, Carvajal-Huerta L, Ruiz-Cabezas JC, Thiene G, Saffitz JE. Structural and
molecular pathology of the heart in Carvajal syndrome. Cardiovasc Pathol.
2004;13:26-32. ).

Best regard

Andrés Ricardo Pérez Riera

--------------------------------------------------------

Portugues

Prezado Prof Guy: 
Similarmente na chamada syndrome de Carvajal (Carvajal-Huerta L. Epidermolytic 
palmoplantar keratoderma with woolly hair and dilated cardiomyopathy. J Am 
Acad Dermatol. 1998; 39:418-421.)  uma entidade autossômica recessiva 
cardio-cutânea mapeada no braço curto do cromossomo 6 (6p24) e causada pela 
mutação 7901 G no exon 24 da desmoplaquina. Esta é uma proteína intracelular 
que ocasiona a união dod desmosomos e adesão de filamentos do cito esqueleto. 
Esta causa deleição prematura do codon localizado no aminoácido de número 18, 
causando truncação do domínio C-terminal na região que interatua com 
filamentos intermediários

Os desmosomas são os elementos de adesão celular na junção entre as células
e são particularmente abundantes na epiderme e no tecido cardíaco onde são
importantes para conferir a rigidez e a elasticidade das células. Os
desmossomos consistem em várias proteínas das quais a desmoplakin é a mais
abundante.

Norgett et al. descreveram a primeira mutação humana recessiva 7901delG,
no gene desmoplaquin o qual ocasiona queratoderma estriada generalizada,
afetando particularmente a epiderme palmo-plantar, cabelos lanosos e
cardiomiopatia dilatada. Há marcada diminuição da quantidade de  sinal
imunorativo de desmoplaquina, plaqoglobina e proteínas gap junction connexin
43 nos discos intercalados. Mostrando um padrão intracelular normal porém,
com o defeito localizado nos discos intercalados. (Kaplan SR, Gard JJ,
Carvajal-Huerta L, Ruiz-Cabezas JC, Thiene G, Saffitz JE. Structural and
molecular pathology of the heart in Carvajal syndrome. Cardiovasc Pathol.
2004;13:26-32. ).

Saludações

Andrés Ricardo Pérez Riera.

 _______________________________________
>
> English - Spanish
>
> This is a problem that I like to discuss. I hope that Dr Dubner will be
> able to show my slide and discussion based on systematic study of the
> socalled "normal right ventricle"****. In my opinion, in addition to what
> you have said Minor form of myocarditis can produce fibrosis and subsequent
> changes similar to ARVD. This is why we are looking for a more precise
> histologic marker.
> We have seen and published (Kaplan HRS 2004 new journal soon in pubmed...)
> that in Naxos disease there is a definite decrease in RV gap junctions,
> however this feature has not been established in ARVD. However this seems
> to me highly probable because C Guiraudon the pathologist has demonstrated
> the presence desmosomes alteration in ARVD (Europ Heat J). This was for me
> the stating point for the investigation in Naxos which is recessive
> syndromic with a strong phenotypic presentation.
> I also think that in you position in Garches you have the material of
> deaths related to car accident providing an interesting pathologic material
> of  so called "normal right ventricle".
> I join the Fontaliran study on 85 specimen however I am sure that it will
> be transferred properly on the Net.
>
> Guy
>
> SEE THE FILE
> http://www.arvd-symposium.org/files/GradeFat.jpg
>
> SEE THE LECTURE "A mini-Atlas of ARVD Pathology"
> http://www.arvd-symposium.org/lectures.shtml
>
> --------------------
>
> Este es un problema que me gusta discutir. Espero que el Dr. Dubner sea
> capaz de mostrar mis diapositivas y discusion en base al estudio
> sistematico del llamado "ventriculo derecho normal"****. En mi opinion,
> ademas de lo que Ud. ha dicho, la forma menor de miocarditis puede producir
> fibrosis y cambios subsiguientes similares a la DAVD. Esta es la razon por
> la que estamos buscando un marcador histologico mas preciso.
> Hemos visto y publicado (Kaplan HRS 2004 new journal soon in pubmed...) que
> en la enfermedad de Naxos hay una disminucion definitiva en las uniones
> "gap" del VD, sin embargo, esta caracteristica no se ha establecido en la
> DAVD. Sin embargo, a mi me parece que esto es altamente probable porque C.
> Guiraudon, el patologo, ha demostrado la presencia de alteracion
> desmosomica en la DAVD (Europ Heat J). Para mi, este fue el punto de inicio
> para la investigacion de Naxos, que es un sindrome recesivo, con una
> presentacion fuertemente fenotipica.
> Tambien creo que en su lugar en Garches, Ud. tiene el material de muertes
> relacionadas con accidentes de autos, que ofrecen un interesante material
> patologico del llamado "ventriculo derecho normal".
> Me uni al estudio Fontaliran con 85 muestras, sin embargo, estoy seguro de
> que se transferira adecuadamente a Internet.
>
> Guy
>
> VER EL ARCHIVO
> http://www.arvd-symposium.org/files/GradeFat.jpg
>
> VER LA CONFERENCIA "A mini-Atlas of ARVD Pathology"
> http://www.arvd-symposium.org/lectures.shtml
>
>  _______________________________________
>
> > English - Spanish
> >
> > Dear colleagues,
> > Significant fat infiltration of the right ventricle which can be found in
> > autopsy cases always raises the question of a possible underlying ARVD.
> > The difficulty is that such right ventricular lipomatosis can be
> > associated with small foci of fibrosis, especially if there is a small
> > degree atheromatous stenosis, an obesity or a chronic alcohol disease. In
> > such cases, what are the pathological criteria useful to make the
> > differential diagnosis? And do you know if such lipomatosis can induce
> > lethal arrhythmias even if is not a true ARVD?
> >
> > I thank you in advance for your answer.
> >
> > Best regards
> > Geoffroy Lorin de la Grandmaison, MD
> > Department of Pathology and Forensic Medicine, Raymond Poincaré Hospital,
> > Garches, France
> >
> > ---------------------
> >
> > Estimados colegas:
> > La infiltracion adiposa significativa del ventriculo derecho que puede
> > encontrarse en los casos de autopsia siempre hace surgir la cuestion de
> > una posible DAVD subyacente. La dificultad es que tal lipomatosis del
> > ventriculo derecho puede asociarse con pequenios focos de fibrosis,
> > especialmente si hay un grado menor de estenosis ateromatosa, obesidad o
> > alcoholismo cronico. En tales casos, cuales son los criterios patologicos
> > utiles para hacer un diagnostico diferencial? Y saben si tal lipomatosis
> > puede inducir arritmias letales incluso si no es verdadera DAVD?
> >
> > Desde ya les agradezco su respuesta.
> >
> > Saludos cordiales,
> >
> > Geoffroy Lorin de la Grandmaison, MD
> > Department of Pathology and Forensic Medicine, Raymond Poincaré Hospital,
> > Garches, France