We read with interest the report by Lampe AK et al. [1] presenting a
patient with Laugier-Hunziker syndrome (LHS) whom had been extensively
investigated in order to rule out Peutz-Jeghers syndrome (PJS).
In the case presented by Lampe AK et al.[1] biopsy specimen of the
lip was twice mislabled as consistent with PJS, which prompted clinicians
to undertake repeated unnecessary in...
We read with interest the report by Lampe AK et al. [1] presenting a
patient with Laugier-Hunziker syndrome (LHS) whom had been extensively
investigated in order to rule out Peutz-Jeghers syndrome (PJS).
In the case presented by Lampe AK et al.[1] biopsy specimen of the
lip was twice mislabled as consistent with PJS, which prompted clinicians
to undertake repeated unnecessary investigations. It should be emphasized
that while LHS may clinically resemble PJS, histological features are
different and distinctive in each condition. Indeed lesions in LHS display
increased basal keratinocytes melanin content without melanocytic
hyperplasia in addition to superficial pigmentary incontinence with dermal
melanophages.[2] In contrast, macules of the Peutz-Jeghers syndrome have
the appearance of lentigines on biopsy, showing expansion of the
melanocytic population, which accounts for the denomination “periorificial
lentiginosis” commonly used to designate the lips and cutaneous lesions of
this entity.[3,4] Of note is that questionable cases reported in the
literature in whom no PJS or LHS diagnosis could be definitely ascertained
had not undergone histological analysis of pigmentary lesions.[5]
While advances in genetics represent exciting breakthroughs and offer
valuable tools for modern medicine, we believe that clinicians should
refrain from routinely using genetic screening tests for diagnostic
purposes when accurate diagnosis can be achieved through careful yet
simple anatomo-clinical correlation.
References
(1) Lampe AK, Hampton PJ, Woodford-Richens K, Tomlinson I, Lawrence
CM, Douglas FS. Laugier-Hunziker syndrome: an important differential
diagnosis for Peutz-Jeghers syndrome. J Med Genet 2003;40:e77.
(2) Dupré A, Viraben R. Laugier’s disease. Dermatologica 1990;181:183-6.
(3) Calnan CD. The Peutz-Jeghers syndrome. Trans St John’s Hosp Dermatol Soc 1960;44:58-64.
(4) Ortonne JP. Les troubles de la pigmentation cutanée. In Dermatologie et maladies
sexuellement transmissibles, 3rd edition, Saurat
JH, Grosshans E, Laugier P, Lachapelle JM, (Eds). Masson, Paris, 1999:407-426.
(5) Gerbig AW, Hunziker T. Idiopathic lenticular mucocutaneous
pigmentation or Laugier-Hunziker syndrome with atypical features. Arch
Dermatol 1996;132:844-5.
We read with interest the work by Burglen et al.[1]
We really appreciate their attempt to provide a careful differential
diagnosis with other rare syndromes whose pathogenesis is still unknown.
We observed one patient with Myhre syndrome [2] and another one affected
by geleophysic dysplasia [3] and find their ta...
We read with interest the work by Burglen et al.[1]
We really appreciate their attempt to provide a careful differential
diagnosis with other rare syndromes whose pathogenesis is still unknown.
We observed one patient with Myhre syndrome [2] and another one affected
by geleophysic dysplasia [3] and find their table 2 very useful in
everyday clinical practice.
However, after their report of 4 more male
patients with Myhre syndrome, we do not agree with their conclusion about
the inheritance of the disease. They observe that paternal age was
increased in half of the reported cases, suggesting a new mutation of an
autosomal dominant gene. They also state that X linked transmission cannot
be excluded since all reported cases (11/11) were males.
The probability to observe 11 consecutive male patients is 1/2064, e.g.
less than 5%, that is the usual value indicating statistical significance.
Moreover, mean paternal age at birth is 35 years but the range is wide,
varying from 23 to 43 years. So, we think that a X-linked pattern of
inheritance is more likely in Myhre syndrome.
That could be an important data to plan further investigation about the
molecular basis of the disease. All reported cases are sporadic. So, a
candidate gene approach is the only possibility to date. Our findings of
abudant close-packed collagen fibers at skin biopsy could be a key-point
to identify possible candidate genes involved in collagen metabolic
pathway localized on the X chromosome.
Understanding the pathogenesis of Myhre syndrome could provide further
clues to identify the molecular basis of similar syndromes.
References
(1) L Burglen, D Héron, A Moerman, A Dieux-Coeslier, J-P Bourguignon, A Bachy, J-C Carel, V Cormier-Daire, S Manouvrier, A Verloes. Myhre syndrome: new reports, review, and differential diagnosis. J Med Genet 2003;40:546-551.
(2) Titomanlio L, Della Casa R, Lecora M, Farina V, Sebastio G, Andria
G, Parenti G. Geleophysic dysplasia: 7-year follow-up study of a patient
with an intermediate form. Am J Med Genet 1999; 86:82-5.
(3) Titomanlio L, Marzano MG, Rossi E, D’Armiento M, De Brasi D, Vega
GR, Andreucci MV, Orsini AVM, Santoro L and Sebastio G. Case
of Myhre syndrome with autism and peculiar skin histological findings. Am J Med Genet 2001;103:163-5.
Desbuquois dysplasia is a rare autosomal recessive chondrodysplasia
characterized by markedly short stature of prenatal onset, joint laxity,
facial dysmorphism including round face, prominent bulging eyes and
midface hypoplasia.
The radiological findings include a ‘Swedish key’
appearance of the proximal femur, advanced carpal and tarsal bone age and
typical hand changes consisting in an extra o...
Desbuquois dysplasia is a rare autosomal recessive chondrodysplasia
characterized by markedly short stature of prenatal onset, joint laxity,
facial dysmorphism including round face, prominent bulging eyes and
midface hypoplasia.
The radiological findings include a ‘Swedish key’
appearance of the proximal femur, advanced carpal and tarsal bone age and
typical hand changes consisting in an extra ossification center distal to
the second metacarpal, delta phalanx, bifid distal phalanx of the thumb,
and phalangeal dislocations.[1-3] However, those typical hand anomalies are
only observed in a third to a half of all Desbuquois patients.[3-4] We have recently reported linkage of a Desbuquois dysplasia disease gene to
chromosome 17q25.3 in a group of patients with typical hand
abnormalities.[5]
Here, we report on the exclusion of the 17q25.3 locus in
three inbred Desbuquois families without typical hand abnormalities. The
families originate from Turkey, Asia and Morocco. Two out of the three
families had been previously reported.[3,6] Their main clinical and
radiological features are summarized in Table 1 (see below).
All affected individuals
fulfilled the criteria for Desbuquois dysplasia, namely short stature of
prenatal onset, joint laxity, specific facial dysmorphism (see Figure 1), a
‘Swedish key’ appearance of the proximal femur and advanced carpal and
tarsal bone age. None of the patients presented any typical hand changes
(absence of extra ossification center distal to the second metacarpal,
absence of delta phalanx or bifid distal phalanx of the thumb, see Figure 2a).
Informed consent and blood samples were obtained from the probant and
other family members when available. Genomic DNA was purified from
peripheral blood leukocytes according to standard techniques.
Microsatellite DNA markers from the 17q25.3 region were used at an average
spacing of 2 cM and were chosen from the Généthon map. PCR analyses were
performed using a single set of primers in each amplification reaction.
The homozygosity mapping strategy was based on the assumption that
affected individuals of the same kindred are homozygous by descent.[7] The
three affected individuals from families 1-3 were heterozygous for the
17q25.3 region (see Figure 3). These results allow us to exclude this region
as the disease locus in Desbuquois families with no hand anomalies and
demonstrate a genetic heterogeneity. Reviewing the 6 sibship reported in
the literature with Desbuquois dysplasia,[1,2,8] we found a complete
intrafamilial concordance regarding the presence or absence of typical
hand anomalies. Indeed, those anomalies were present in all individuals
within the 2 sibships reported by Puissan and in the 3 sibships reported
by Shohat.[8] Moreover, they were absent in the sibpair reported by
Desbuquois. Those findings together with our molecular results suggests
that the presence or absence of hands anomalies define two distinct
entities within Desbuquois dysplasia. These results emphasise the
importance of defining subgroups prior to any linkage analyses. Additional
families will be necessary to confirm this result.
Figure 1 [View Figure 1]
Clinical presentation of patient 1 at age 1 and age 11.
Note typical facial dysmorphism (round and flat face, prominent bulging eyes and midface hypoplasia), prominent sternum, micromelia and brachydactyly.
Figure 2 [View Figure 2] (a,b) X-rays of the hands of patient 2 (a) and 3 (b), respectively at age
5 years and 15 days. Note the advanced bone age and the generalised
brachydactyly but the absence of typical hand changes (ie extra
ossification center distal to the second metacarpal, delta phalanx, bifid
distal phalanx of the thumb.) (c) X-rays of the pelvis in patient 2 at 6 years of age. Note the typical
'Swedish key' appearance of the proximal femur.
Figure 3 [View Figure 3]
Pedigrees and haplotypes of the 17q25.3 region in families
1-3. The microsatellite polymorphic markers were placed according to the
Généthon and the Human Genome working Draft databases, from D17S802 to
D17S784, centromere to telomere. Genetic intervals between following
markers were respectively of 4.1, 1.7, 1.4, 2.3 and 0 cM. Two additional
microsatellite DNA markers were chosen on clones AC016182 and AC099804
between D17S802 and D17S1847 in order to establish heterozygosity for the
17q25.3 region in family 1.
References
(1) Desbuquois G, Grenier B, Michel J, Rossignol C. Nanisme
chondrodystrophique avec ossification anarchique et polymalformations chez
deux sœurs. Arch Fr Pediatr 1966; 23: 573-587.
(2) Puissan C, Maroteaux P, Castroviejo I, Risbourg B. Dysplasie osseuse
avec nanisme et altérations squelettiques diffuses. Six observations. Arch
Fr Pediatr 1975;32:541-550.
(3) Gillessen-Kaesbach G, Meinecke P, Ausems MGEM, Nöthen M, Albrecht B,
Beemer FA, Zerres K. Desbuquois syndrome: three further cases and review
of the literature. Clin Dysmorphol 1995;4:136-144.
(4) Faivre L, Cormier-Daire V, Eliot A, Field F, Munnich A, Maroteaux P, Le
Merrer M, Lachman R. Desbuquois dysplasia, a reevaluation with abnormal
and “ normal ” hands : Radiographic manifestations. Am J Med Genet; in
press.
(5) Faivre L, Le Merrer M, Al Gazali LI, Aussems MGEM, Bitoun P, Munnich A,
Cormier-Daire V. Homozygosity mapping of a Desbuquois dysplasia locus to
chromosome 17q25.3. J Med Genet 2003;40:282-284.
(6) Le Merrer M, Young ID, Stanescu V, Maroteaux P. Desbuquois syndrome. Eur
J Pediatr 1991;150:793-796.
(7) Lander ES, Botstein D. Homozygosity mapping: a way to map human
recessive traits with the DNA of inbred children. Science 1987;236:1567-1570.
(8) Shohat M, Lachman R, Gruber HE, Hsia YE, Golbus MS, Witt DR, Bodell A,
Bryke CR, Hogge WA, Rimoin DL. Desbuquois syndrome: clinical,
radiographic, and morphologic characterization. Am J Med Genet 1994;52:9-18.
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....
Dear Editor
We read with interest the report by Lampe AK et al. [1] presenting a patient with Laugier-Hunziker syndrome (LHS) whom had been extensively investigated in order to rule out Peutz-Jeghers syndrome (PJS).
In the case presented by Lampe AK et al.[1] biopsy specimen of the lip was twice mislabled as consistent with PJS, which prompted clinicians to undertake repeated unnecessary in...
Dear Editor
We read with interest the work by Burglen et al.[1]
We really appreciate their attempt to provide a careful differential diagnosis with other rare syndromes whose pathogenesis is still unknown. We observed one patient with Myhre syndrome [2] and another one affected by geleophysic dysplasia [3] and find their ta...
Dear Editor
Desbuquois dysplasia is a rare autosomal recessive chondrodysplasia characterized by markedly short stature of prenatal onset, joint laxity, facial dysmorphism including round face, prominent bulging eyes and midface hypoplasia.
The radiological findings include a ‘Swedish key’ appearance of the proximal femur, advanced carpal and tarsal bone age and typical hand changes consisting in an extra o...
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...
Pages