No doubt the standards of care vary with time, location, and
affordability. I described (with my colleagues) a patient with 13 trisomy
who had a long survival the last time I saw her in 1995, 12 years (see
Delaware Med J 1985;57:629-634 and Delaware Med J 1987;59:105-106, also see www.wiley.com/borgaonkar). We also have...
No doubt the standards of care vary with time, location, and
affordability. I described (with my colleagues) a patient with 13 trisomy
who had a long survival the last time I saw her in 1995, 12 years (see
Delaware Med J 1985;57:629-634 and Delaware Med J 1987;59:105-106, also see www.wiley.com/borgaonkar). We also have described the longest surviving
triploid (69,XXY) infant (Amer J Med Genet 1986; 25:307-312).
At present, while working with patients with Late Onset Alzheimer's
Disease, I find that longer survival (upto 15 years or more) is possible
inspite of acute medical problems, when, as Dr Bawle points out
appropriate medical care is available. All these points need to be
included when discussing prognosis with individuals/families and
management of genetically affected individuals.
One of the interesting findings in this study is the lack of a change in length of survival over the study period. It appears that modern intensive care has not made any impact. Indeed, rapid and accurate diagnosis with early withdrawal of care following discussion with the parents may reduce the survival period. It is interesting that, Dr Rassmusen from the CDC in Atlanta presented new population based dat...
One of the interesting findings in this study is the lack of a change in length of survival over the study period. It appears that modern intensive care has not made any impact. Indeed, rapid and accurate diagnosis with early withdrawal of care following discussion with the parents may reduce the survival period. It is interesting that, Dr Rassmusen from the CDC in Atlanta presented new population based data at the recent ASHG
meeting suggesting that there is a reduction rather than an increase in survival over time. I fully agree that we need more information in this area and I would encourage all neonatal intensive care units to record the
actual cause of death (e.g. central apnoea, respiratory disress, cariac failure etc) in addition to accurate cateloging of associated major malformations.
Many articles written on the age of survival of babies with trisome
13 and 18 fail to factor in the influence of modern intensive care
treatment modalities.
Use of artificial respirators, suctioning of respiratory secretons
coupled with supplemental oxygen and nasogastric tube feedings may prolong
survival.For the survivors beyond 7-10 days, it has become routine to feed
these babies with tube f...
Many articles written on the age of survival of babies with trisome
13 and 18 fail to factor in the influence of modern intensive care
treatment modalities.
Use of artificial respirators, suctioning of respiratory secretons
coupled with supplemental oxygen and nasogastric tube feedings may prolong
survival.For the survivors beyond 7-10 days, it has become routine to feed
these babies with tube feedings in US and even a gastrostomy is done.
Gastroesophageal reflux is treated with pharmacotherapy.
In other words, are these survival tables truly reflective of the
natural history of these trisomies? We need these factors included in the
survival tables in order to use them for genetic counselling. Perhaps
survival data from countries which do not provide such modern treatments
would be useful.
I would like to draw to the attention of your readers that the pair
of twins described in this report[1] are the same twins that we described in
our paper Tuckerman et al.[2] I feel that failing to directly quote our paper was rather an oversight
by Willemsen et al. on a number of counts.
First, our paper contains a more detailed family history and
description of the twins...
I would like to draw to the attention of your readers that the pair
of twins described in this report[1] are the same twins that we described in
our paper Tuckerman et al.[2] I feel that failing to directly quote our paper was rather an oversight
by Willemsen et al. on a number of counts.
First, our paper contains a more detailed family history and
description of the twins. The description of the unaffected twin in
Willemsen's report is inaccurate, as
she has completed tertiary education and works in a professional
capacity. Second, it is an interesting observation that the differing X-inactivation patterns that we found in the two sisters using cytogenetic
analysis is very similar to that Williamsen et al. observed using molecular
studies of hair root cells.
However, the most important point is that failure to identify
genetically interesting families will lead to more examples of one case
history being reported as two. The result of which may result in an
overestimation of the prevalence of these conditions. To prevent this from
happening I would like to make a case for the introduction of an agreed
anonymous nomenclature or coding to identify published cases. I suggest
that a database is then set up with restricted access via the Internet.
References
(1) Willemsen R, Olmer R, De Diego Otero Y, Oostra BA. Twin sisters, monozygotic with the fragile X mutation, but with a different phenotype. J Med Genet 2000;37: 603-60.
(2) Tuckerman EM, Webb T, Bundey S. Frequency and replication status of the Fragile X FRA(X)(q27-28). J Med Genet 1985;22:85-91.
The title of the article by Rio et al. in this month's Journal
"Automated fluorescent genotyping detects 10 % of cryptic subtelomeric
rearrangements in idiopathic syndromic mental retardation" is incorrect
and very misleading. The title as publsihed clearly means that automated
fluorescent genotyping fails to detect 90 % of subtelomeric rearrangements
in idiopathic syndromic mental retardation. Ev...
The title of the article by Rio et al. in this month's Journal
"Automated fluorescent genotyping detects 10 % of cryptic subtelomeric
rearrangements in idiopathic syndromic mental retardation" is incorrect
and very misleading. The title as publsihed clearly means that automated
fluorescent genotyping fails to detect 90 % of subtelomeric rearrangements
in idiopathic syndromic mental retardation. Even a brief perusal of the
abstract shows that the data in the paper show no such thing. The authors
identified cryptic subtelomeric rearrangements in 14 of 150 patients
studied, and asserted that "This study clearly shows that fluorescent
genotyping is a sensitive and cost effective method...". May I suggest an
erratum giving a revised title which carries the intended meaning:
"Automated fluorescent genotyping detects cryptic subtelomeric
rearrangements in 10 % of patients with idiopathic syndromic mental
retardation"?
Reference
M Rio, F Molinari, S Heuertz, C Ozilou, P Gosset, O Raoul, V Cormier-Daire, J Amiel, S Lyonnet, M Le Merrer, C Turleau, M-C de Blois, M Prieur, S Romana, M Vekemans, A Munnich, L Colleaux. Automated fluorescent genotyping detects 10% of cryptic subtelomeric rearrangements in idiopathic syndromic mental retardation. J Med Genet 2002;39:266-70.
Thank you for an interesting paper on the relationships between DM1
and reproductive function. The occurrence of testicular failure(endocrine
and exocrine )in males with DM1 is well documented in the literature. A
careful search for ovarian failure or compromised ovarian function in the
female with DM1 has been infrequently recognized or infrequebtly studied. I
have had a 31 year old patient with DM1 and...
Thank you for an interesting paper on the relationships between DM1
and reproductive function. The occurrence of testicular failure(endocrine
and exocrine )in males with DM1 is well documented in the literature. A
careful search for ovarian failure or compromised ovarian function in the
female with DM1 has been infrequently recognized or infrequebtly studied. I
have had a 31 year old patient with DM1 and ovarian failure(46,XX). I
wonder if the age onset for ovarian failure may be closer to the natural
menopause and difficult to determine or the early, less apparent symptoms
of DM1 are overlooked by the gynecologist when the diagnosis of ovarian
failure is finalized. The measurement of cycle day 3 serum FSH might be
informative in this regard. It would be interesting to hear the long term
follow up on your cases,and your comments.
My co-authors and I are grateful to Professor Winter for drawing this
point to our attention. The baby was found to have a tracheo-oesophageal
fistula and oesophageal atresia which were the subject of surgical
correction on day 2 of life. These findings strengthened concerns with
respect to VATER association. I regret that the inadvertant omission of
these clinical data have led to any confusion an...
My co-authors and I are grateful to Professor Winter for drawing this
point to our attention. The baby was found to have a tracheo-oesophageal
fistula and oesophageal atresia which were the subject of surgical
correction on day 2 of life. These findings strengthened concerns with
respect to VATER association. I regret that the inadvertant omission of
these clinical data have led to any confusion and welcome this opportunity
to clarify.
May I assure Professor Winter, from a country where the health
service relies heavily on miracles in the absence of any meaningful state
funding for beds, doctors, nurses, laboratory staff, equipment or
facilities, that it is indeed heartening to learn that our observations
are deemed to be "a significant contribution to the literature" in other,
more heady environments. It is one of our few consolations to learn that
distinguished colleagues elsewhere might consider our report to be worthy
of their attention. It would indeed be wonderful to see our contribution
highlighted in the London Dysmorphology Database, v 3, though it will
require either a miracle or Professor Winter's philantrophy for this
author to see it. If I don't hear from Professor Winter, I shall start
praying....
The single case report of a child with features of VATER association
and a PTEN mutation by Reardon et al., (2001) is certainly a significant
contribution to the literature. I am going to highlight it prominently in
the London Dysmorphology Database (Winter and Baraitser, 2001) (ver. 3
with significant enhancements now available from Oxford University Press).
However the case report is somewhat puz...
The single case report of a child with features of VATER association
and a PTEN mutation by Reardon et al., (2001) is certainly a significant
contribution to the literature. I am going to highlight it prominently in
the London Dysmorphology Database (Winter and Baraitser, 2001) (ver. 3
with significant enhancements now available from Oxford University Press).
However the case report is somewhat puzzling. The infant was found to have
an absent stomach bubble and polyhydramnios on ultrasonography. This was
interpreted as indicating a probable tracheo-oesophageal fistula. As far
as I am aware, an isolated tracheo-oesophageal fistula would not cause an
absent stomach bubble, unless associated with oesophageal atresia. Even
more surprising, postnatally this abnormality appears to have disappeared,
as there is no mention of investigation or treatment. I realise the
patient is probably from Ireland, where such miracles are relatively
frequent, but it would be useful to know if this malformation was
confirmed, as obviously the presence of an oesophageal abnormality
increases the overlap with VATER association. Could the authors clarify
this point?
Professor Robin M Winter
Department of Clinical Genetics
Institute of Child Health
London
Reference
Reardon W, Zhou X-P, Eng C (2001). A novel germline mutation of the PTEN
gene in a patient with macrocephaly, ventricular dilatation, and features
of VATER association. J Med Genet 2001;38:820-823.
I read with great interest this article on the mapping of an isolated
form of X-linked cataract on Xp22. As the authors state it is highly
probable that the condition in this family is an allelic form of Nance-
Horan syndrome (NHS) or cataract-dental syndrome. Although OMIM database
distinguishes NHS (MIM 302350) from two forms of isolated X-linked
congenital cataract - X-linked congenital cataract with po...
I read with great interest this article on the mapping of an isolated
form of X-linked cataract on Xp22. As the authors state it is highly
probable that the condition in this family is an allelic form of Nance-
Horan syndrome (NHS) or cataract-dental syndrome. Although OMIM database
distinguishes NHS (MIM 302350) from two forms of isolated X-linked
congenital cataract - X-linked congenital cataract with posterior sutural
opacities in heterozygotes (MIM 302200) and X-linked congenital cataract
with microcornea or slight microphthalmia (MIM 302300) - there are some
arguments suggesting that this distinction may not be justified. This
classification was based on old publications, and these two forms of X-
linked cataract without dental anomalies were described before NHS was
recognized as a distinct entity. Microcornea is part of NHS and has also
been reported in some patients within families affected with cataract from
the first group (MIM 302200) and posterior lens opacities are usually
present in NHS heterozygotes. It is highly probable that NHS was not
recognized in some families as the dental anomalies may be easily missed.
One of the NHS families included in our linkage analysis (family 2) [1]
was initially thought to be affected with an isolated X-linked cataract as
the affected males were not markedly dysmorphic and their teeth anomalies
were mild. Moreover the family reported by Krill et al. in 1969 [2], and
considered as the most convincing example of isolated X-linked congenital
cataract, was later recognized as a NHS family [3] and was included in a
linkage analysis [4]. Finally, it appears that the family described by
Waardenburg et al. in 1961 [5] and registered in OMIM database as an
isolated cataract belonging to the second group (MIM 302300), was the same
as that reported eighteen years later by van Dorp and Delleman [6] and was
ultimately recognized as a NHS family [7]. Considering this marked
phenotypic overlap, it is tempting to say that these three groups of X-
linked cataracts probably correspond to a single condition with variable
expression. The report of a first locus for isolated X-linked cataract on
Xp22 in a region overlapped by the NHS genetic interval strongly supports
this hypothesis.
References
(1) Toutain A, Ronce N, Dessay B, Robb L, Francannet C, Le Merrer M, Briard
ML, Kaplan J, Moraine C. Nance-Horan syndrome: linkage analysis in 4
families refines localisation to Xp22.31-p22.13. Hum Genet 1997;99:256-61.
(2) Krill AE, Woodbury G, Bowman JE. X-chromosomal-linked sutural
cataracts. Am J Ophthal 1969;68:867-872.
(3) Lewis RA, Nussbaum RL, Stambolian D. Mapping X-linked ophthalmic
diseases. IV. Provisional assignment of the locus for X-linked congenital
cataracts and microcornea (the Nance-Horan syndrome) to Xp22.2-Xp22.3.
Ophthalmology 1990;97:110-121.
(4) Stambolian D, Lewis RA, Buetow K, Bond A, Nussbaum R. Nance-Horan
syndrome: localization within the region Xp21.1-Xp22.3 by linkage
analysis. Am J Hum Genet 1990;47:13-19.
(5) Waardenburg PJ, Franceschetti A, Klein D. Genetics and Ophthalmology.
Vol. 1. Springfield, III.: Charles C Thomas (pub.) 1961. Pp. 880.
(6) van Dorp DB, Delleman JW. A family with X-chromosomal recessive
congenital cataract, microphthalmia, a peculiar form of the ear and dental
anomalies. J Pediat Ophthal Strabismus 1979;16:166-171.
(7) Bergen AAB, ten Brink J, Schuurman EJM, Bleeker-Wagemakers EM. Nance-
Horan syndrome: linkage analysis in a family from the Netherlands.
Genomics 1994;21:238-240.
Although I lack expertise in screening methods designed to detect the
presence of mutations that predispose to disease, the findings reported on
BRCA1 by Eng et al. are clearly important. It is essential that a
systematic blinded comparison of methods should be carried out to
establish or confirm the validity of genetic screening tests. This is of
particular importance in cases where the predisposing ris...
Although I lack expertise in screening methods designed to detect the
presence of mutations that predispose to disease, the findings reported on
BRCA1 by Eng et al. are clearly important. It is essential that a
systematic blinded comparison of methods should be carried out to
establish or confirm the validity of genetic screening tests. This is of
particular importance in cases where the predisposing risk of cancer
associated with the mutations is high and the individuals tested must make
important decisions based on the outcome of such tests. Hence, the
scientific and medical communities are obliged to assure the accuracy and
reliablity of tests offered to identify mutations that carry profound
consequences for the individual patient.
Dear Editor
No doubt the standards of care vary with time, location, and affordability. I described (with my colleagues) a patient with 13 trisomy who had a long survival the last time I saw her in 1995, 12 years (see Delaware Med J 1985;57:629-634 and Delaware Med J 1987;59:105-106, also see www.wiley.com/borgaonkar). We also have...
Dear Editor
One of the interesting findings in this study is the lack of a change in length of survival over the study period. It appears that modern intensive care has not made any impact. Indeed, rapid and accurate diagnosis with early withdrawal of care following discussion with the parents may reduce the survival period. It is interesting that, Dr Rassmusen from the CDC in Atlanta presented new population based dat...
Dear Editor
Many articles written on the age of survival of babies with trisome 13 and 18 fail to factor in the influence of modern intensive care treatment modalities.
Use of artificial respirators, suctioning of respiratory secretons coupled with supplemental oxygen and nasogastric tube feedings may prolong survival.For the survivors beyond 7-10 days, it has become routine to feed these babies with tube f...
Dear Editor
I would like to draw to the attention of your readers that the pair of twins described in this report[1] are the same twins that we described in our paper Tuckerman et al.[2] I feel that failing to directly quote our paper was rather an oversight by Willemsen et al. on a number of counts.
First, our paper contains a more detailed family history and description of the twins...
Dear Editor
The title of the article by Rio et al. in this month's Journal "Automated fluorescent genotyping detects 10 % of cryptic subtelomeric rearrangements in idiopathic syndromic mental retardation" is incorrect and very misleading. The title as publsihed clearly means that automated fluorescent genotyping fails to detect 90 % of subtelomeric rearrangements in idiopathic syndromic mental retardation. Ev...
Dear Editor
Thank you for an interesting paper on the relationships between DM1 and reproductive function. The occurrence of testicular failure(endocrine and exocrine )in males with DM1 is well documented in the literature. A careful search for ovarian failure or compromised ovarian function in the female with DM1 has been infrequently recognized or infrequebtly studied. I have had a 31 year old patient with DM1 and...
Dear Editor,
My co-authors and I are grateful to Professor Winter for drawing this point to our attention. The baby was found to have a tracheo-oesophageal fistula and oesophageal atresia which were the subject of surgical correction on day 2 of life. These findings strengthened concerns with respect to VATER association. I regret that the inadvertant omission of these clinical data have led to any confusion an...
Dear Editor,
The single case report of a child with features of VATER association and a PTEN mutation by Reardon et al., (2001) is certainly a significant contribution to the literature. I am going to highlight it prominently in the London Dysmorphology Database (Winter and Baraitser, 2001) (ver. 3 with significant enhancements now available from Oxford University Press). However the case report is somewhat puz...
Dear Editr
I read with great interest this article on the mapping of an isolated form of X-linked cataract on Xp22. As the authors state it is highly probable that the condition in this family is an allelic form of Nance- Horan syndrome (NHS) or cataract-dental syndrome. Although OMIM database distinguishes NHS (MIM 302350) from two forms of isolated X-linked congenital cataract - X-linked congenital cataract with po...
Dear Editor
Although I lack expertise in screening methods designed to detect the presence of mutations that predispose to disease, the findings reported on BRCA1 by Eng et al. are clearly important. It is essential that a systematic blinded comparison of methods should be carried out to establish or confirm the validity of genetic screening tests. This is of particular importance in cases where the predisposing ris...
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