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.
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.
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.
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.
In their electronic letter Smith et al.[1] claim to have found evidence that adult Prader-Willi syndrome (PWS) patients with maternal uniparental disomy (UPD) have an increased mortality compared to PWS patients with deletion (Del). The main results can be summarised as in Table 1.
In their electronic letter Smith et al.[1] claim to have found evidence that adult Prader-Willi syndrome (PWS) patients with maternal uniparental disomy (UPD) have an increased mortality compared to PWS patients with deletion (Del). The main results can be summarised as in Table 1.
Dead
Alive
Total
UPD
4
4
8
Del
5
17
22
Total
9
21
30
Table 1 Prader-Willi syndrome patients: Number of UPD and Del divided into dead and alive.
Obviously, 50% (4/8) of UPD patients and 23% (5/22) of Del patients died during follow-up. The events are few, and the difference is far from significant (P=0.20; Fisher's exact test). However, Smith et al. claim that 44% (4/9) with UPD died while 18% (4/22) with UPD were still alive. Similar calculations were made for the Del patients, and a P-value of 0.05 is mentioned. These calculations make no sense. We are unable to guess the source of the significant P-value.
A reasonable mortality comparison should include the time at risk; it was 44 years in the UPD group and 95 years in the Del group. A Cox regression gave a hazard ratio of 1.31 (95% CI 0.32-5.33; P=0.37) when comparing UPD with Del, adjusted for age and sex. We are, however, not certain about this result due to inconsistent information in Table 2 concerning age on admission, age at death, and follow-up time for three patients (e.g. patient F13 was 17 years on admission and 22 years at death, but had a follow-up time of 0 years). For these patients we recalculated the follow-up time, using the time span from admission to death.
Thus, the results cannot be considered to give any evidence of an increased mortality among UPD compared to Del patients or vice versa. PWS patients, especially those with UPD, and their families should not have added any further unjustified reason to worry.
Reference
(1) Smith A, Loughnan G, Steinbeck K. Death in adults with Prader-Willi syndrome may be correlated with maternal uniparental disomy. J Med Genet 2003;40:e63.
Regarding the article by Maher et al,[1] it should be noted that the correct method for calculating the required probability would be to use the binomial distribution. (Of course the Poisson approximation is
quite accurate here). However because of the highly skewed nature of the null distribution the appropriate probability for a two sided test is 0.004 ie the one sided
probability should not be dou...
Regarding the article by Maher et al,[1] it should be noted that the correct method for calculating the required probability would be to use the binomial distribution. (Of course the Poisson approximation is
quite accurate here). However because of the highly skewed nature of the null distribution the appropriate probability for a two sided test is 0.004 ie the one sided
probability should not be doubled. Of course, this does not affect the conclusions drawn.
Reference
(1) ER Maher, LA Brueton, SC Bowdin, A Luharia, W Cooper, TR Cole, F Macdonald, JR Sampson, CL Barratt, W Reik, and MM Hawkins. Beckwith-Wiedemann syndrome and assisted reproduction technology (ART). J Med Genet 2003;40:62-64.
We were very interested in the review article on telomeres by de
Vries et al.[1]
The authors comment
that all of the 3p terminal deletions reported in the literature were
microscopically visible, except for two siblings with an unbalanced
familial translocation. We have recently seen a child where we detected a
3p deletion on telomere analysis that was not visible by routine
cytogenetic...
We were very interested in the review article on telomeres by de
Vries et al.[1]
The authors comment
that all of the 3p terminal deletions reported in the literature were
microscopically visible, except for two siblings with an unbalanced
familial translocation. We have recently seen a child where we detected a
3p deletion on telomere analysis that was not visible by routine
cytogenetics.
The child in question was born at 38 weeks weighing 7lb 4 oz. At birth she
had dislocated hips and talipes equinovarus. She had marked dimples around
her ankles and elbows and deep palmar creases. She had notable facial
asymmetry with a right ptosis, mandibular asymmetry and a slightly small
right ear. She was a poor feeder requiring a gastrostomy and on follow-up
it became clear that she was globally developmentally delayed. Cardiac
evaluation revealed atrial and ventricular septal defects. She was
referred to the clinical genetics service at 14 months of age when she was
noted to have trigonocephaly. She also had small finger and toe nails,
especially of the 5th fingers and toes. An MRI scan showed some degree of
frontal lobe atrophy and slightly thin corpus callosum.
This case illustrates the value of telomere screening in selected
patients. Trigonocephaly has not been a clinical feature highlighted in
the discussion about the indications for telomere screening but given the
number of chromosome abnormalities that have been associated with this
finding, we believe that those children with developmental delay and
trigonocephaly should have telomere studies performed if the conventional
cytogenetic analysis is normal and there is no other likely cause such as
anticonvulsant exposure in utero.
Reference
(1) De Vries BBA, Winter R, Schinzel A, van Ravenswaaij-Arts C. Telomeres: a diagnosis at the end of the chromosomes
. J Med Genet 2003;40:385-398.
Smith-Magenis syndrome is a genetic syndrome associated with interstitial
deletions of chromosome 17p11.2. Main features include congenital
anomalies, abnormal behaviour and sleep/wake rhythm abnormalities.[1] The
latter have been shown to result from a reversed circadian rhythm of
melatonin.[2,3] Normally, secretion of melatonin peaks at night and is
minimal during the day. In Smith-Magenis syndrome mel...
Smith-Magenis syndrome is a genetic syndrome associated with interstitial
deletions of chromosome 17p11.2. Main features include congenital
anomalies, abnormal behaviour and sleep/wake rhythm abnormalities.[1] The
latter have been shown to result from a reversed circadian rhythm of
melatonin.[2,3] Normally, secretion of melatonin peaks at night and is
minimal during the day. In Smith-Magenis syndrome melatonin reaches a peak
in the daytime and is lowest during the night.[2,3] This results in early
onset and offset of sleep, frequent waking during the night and
hypersomnia during the day.[1]
The inversion of the circadian rhythm of melatonin in Smith-Magenis
syndrome can be considered as an extremely advanced or an extremely
delayed melatonin rhythm. The therapeutic consequences differ: melatonin
rhythm can maximally be delayed with exogenous melatonin administered 10
hours after endogenous melatonin onset and maximally be advanced by
exogenous melatonin administered 5 hours before endogenous melatonin onset.[4] We hypothesised that sleep disturbances in Smith-Magenis syndrome
result from an extremely advanced melatonin rhythm. Consequently, we
treated a patient with Smith-Magenis syndrome with melatonin, administered
after endogenous melatonin onset.
Case report
A boy with Smith-Magenis syndrome was referred to our outpatient clinic at
age eight years. He had been diagnosed with the syndrome at age three
years, after evaluation for developmental delay. The diagnosis had been
confirmed by demonstration of a 17p11.2 deletion by FISH analysis. At the
time of referral, the boy¡¦s parents reported serious disturbances of both
sleep and behaviour. Mean onset of sleep was at 7.30 pm, with mean waking
at 4.30 am. Moreover, there was frequent nocturnal waking and need for
naps during the day. The main behavioural symptoms experienced were
hyperactivity and tantrums. Because of this uncontrollable behaviour, the
boy had been institutionalised. The boy was treated with a morning regimen
of melatonin alone. Initially, melatonin 3 mg was administered at 4 am.
Over the next weeks, the time of administration was shifted towards 7 am,
and some time later to 8 am. Mean waking was delayed to 7 am, and
disappearance of both night awakenings and the need for naps during the
day were reported. The time of onset of sleep was not influenced by the
treatment. Thus, with treatment mean gain in sleep was two-and-a-half
hours. In addition, behavioural disturbances improved significantly with
this treatment as well. At the time of this report, the boy has been
treated with this regimen for over a year and results have been
consistently positive.
Discussion
Behavioural symptoms and sleep disturbances in Smith-Magenis syndrome have
a major impact on patients and their families. A therapeutic regimen using
beta1-adrenergic antagonists has been reported to improve both behaviour
and sleep disturbances in Smith-Magenis syndrome.[5] More recently,
addition of evening melatonin suppletion to this regimen has been reported
to enhance this positive effect.[6] Nine children were treated with a
combination of morning acebutolol and evening melatonin, which resulted in
a mean delay in sleep onset of 30 minutes and in waking by 60 minutes. The
mean gain in sleep in this report was 30 minutes (rate not mentioned). The
authors do not mention the considerations for administration of melatonin
in the evening. Yet, evening suppletion seems logical, as by this the
melatonin peak is reached at its physiological time at night.
As mentioned, we postulated that sleep disturbances in Smith-Magenis
syndrome result from an extremely advanced melatonin rhythm. From the
observations of the natural sleep-wake rhythm in our patient, we
considered the endogenous melatonin onset to be around 7 p.m. Previous
observations have shown serum melatonin peaks around this time in several
other Smith-Magenis patients.[3,5,6] Consequently, we treated our patient
with melatonin administered several hours after this moment, with the time
of administration gradually being shifted towards a normal waking time.
With this treatment, the boy¡¦s waking time shifted along with the time of
administration. By this, eventual gain in sleep was two-and-a-half hours.
In contrast, De Leersnijder et al. reported a mean gain in sleep of 30
minutes with melatonin and acebutolol, and no gain in sleep as much as two
-and-a-half hours was reached in any of the nine children studied.[6]
This suggests that a treatment regimen with morning melatonin may be more
successful in restoring a normal sleep pattern in Smith-Magenis syndrome
than is treatment with both a beta1-adrenergic antagonist and evening
melatonin. Thus far, our observations have been limited to a single case.
Yet, in our opinion the results of treatment in this case are solid and
may point to a new direction in the search of adequate therapy of sleep
disturbances in Smith-Magenis syndrome.
The observations in this case support our hypothesis that sleep
disturbances in Smith-Magenis syndrome are due to advancement of the
endogenous melatonin rhythm. The circadian disorder in Smith-Magenis
syndrome may well reflect an Advanced Sleep Phase Syndrome, characterised
by an advanced sleep-wake and melatonin rhythm.[7] In this syndrome, a
defect in the Per2 clock gene has been demonstrated,[8] whereas in the
Delayed Sleep Phase Syndrome, characterised by a delayed sleep-wake and
melatonin rhythm, a defective Per3 clock gene has been found.[9] Clock
genes of Smith-Magenis patients are currently under investigation and may
provide further insight in the nature of the underlying sleep syndrome.
References
(1) Greenberg F, Lewis RA, Potocki L, Glaze D, Parke J, Killian J, Murphy
MA, Williamson D, Brown F, Dutton R, McCluggage C, Friedman E, Sulek M,
Lupski JR. Multi-disciplinary clinical study of Smith-Magenis syndrome
(deletion 17p11.2). Am J Med Genet 1996;62(3): 247-54.
(2) Potocki L, Glaze D, Tan DX, Park SS, Kashork CD, Shaffer LG, Reiter RJ,
Lupski JR. Circadian rhythm abnormalities of melatonin in Smith-Magenis
syndrome. J Med Genet 2000;37:428-433.
(3) De Leersnyder H, De Blois, MC, Claustrat B, Romana S, Albrecht U, Von
Kleist-Retzow JC, Delobel B, Viot G, Lyonnet S, Vekemans M, Munnich A.
Inversion of the circadian rhythm of melatonin in the Smith-Magenis
syndrome. J Pediatr 2001;139:111-116.
(4) Lewy AJ, Ahmed S, Jackson JM, Sack RL. Melatonin shifts human circadian
rhythm according to a phase-response curve. Chronobiol Int 1992;9(5):380-392.
(5) De Leersnyder H, De Blois MC, Vekemans M, Sidi D, Villain E, Kindermans
C, Munnich A. ƒÒ1-adrenergic antagonists improve sleep and
behavioural disturbances in a circadian disorder, Smith-Magenis syndrome. J Med Genet 2001;38:586-590.
(6) De Leersnyder H, Bresson JL, De Blois MC, Souberbiele JC, Mogenet A,
Delhotal-Landes B, Salefranque F, Munnich A. ƒÒ1-adrenergic
antagonists and melatonin reset the clock and restore sleep in a circadian
disorder, Smith-Magenis syndrome. J Med Genet 2003; 40:74-78.
(7) Wiz-Justice A, Armstrong SM. Melatonin: nature¡¦s soporific? J Sleep Res
1996; 5(2):137-141.
(8) Toh KL, Jones CR, He Y, Eide EJ, Hinz WA, Virshup DM, Ptacek LJ, Fu YH.
An hPer2 phosphorylation site mutation in familial advanced sleep phase
syndrome. Science 2001;291(5506):1040-1043.
(9) Archer NS, Robilliard DL, Skene DJ, Smits M, Williams A, Arendt J,
Schantz MV. A length polymorphism in the circadian clock gene Per3 is
linked to delayed sleep phase syndrome and extreme diurnal preference. Sleep 2003;26:413-415.
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
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
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
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
In their electronic letter Smith et al.[1] claim to have found evidence that adult Prader-Willi syndrome (PWS) patients with maternal uniparental disomy (UPD) have an increased mortality compared to PWS patients with deletion (Del). The main results can be summarised as in Table 1.
Dear Editor
Regarding the article by Maher et al,[1] it should be noted that the correct method for calculating the required probability would be to use the binomial distribution. (Of course the Poisson approximation is quite accurate here). However because of the highly skewed nature of the null distribution the appropriate probability for a two sided test is 0.004 ie the one sided probability should not be dou...
Dear Editor
We were very interested in the review article on telomeres by de Vries et al.[1]
The authors comment that all of the 3p terminal deletions reported in the literature were microscopically visible, except for two siblings with an unbalanced familial translocation. We have recently seen a child where we detected a 3p deletion on telomere analysis that was not visible by routine cytogenetic...
Dear Editor
Smith-Magenis syndrome is a genetic syndrome associated with interstitial deletions of chromosome 17p11.2. Main features include congenital anomalies, abnormal behaviour and sleep/wake rhythm abnormalities.[1] The latter have been shown to result from a reversed circadian rhythm of melatonin.[2,3] Normally, secretion of melatonin peaks at night and is minimal during the day. In Smith-Magenis syndrome mel...
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