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European Journal of Medical Genetics 51 (2008) 303e314http://www.elsevier.com/locate/ejmg

Original article

Patau syndrome with long survival in a caseof unusual mosaic trisomy 13

Giuseppina Fogu a,*, Emanuela Maserati b, Francesca Cambosu a,Maria Antonietta Moro a, Fausto Poddie a, Giovanna Soro a,

Pasquale Bandiera c, Gigliola Serra d, Gianni Tusacciu d,Giuseppina Sanna d, Vittorio Mazzarello c,

Andrea Montella c

a Clinical Genetics, Department of Biomedical Sciences, University of Sassari, viale San Pietro,

43/C, 07100 Sassari, Italyb Department of Experimental and Clinical Biomedical Sciences, University of Insubria, Varese, Italy

c Anatomy and Histology Division, Department of Biomedical Sciences, University of Sassari, Italyd Institute of Child Neuropsychiatry, University of Sassari, Italy

Received 21 January 2008; accepted 27 March 2008

Available online 9 April 2008

Abstract

We report a 12-year-old patient with Patau syndrome, in whom two cell lines were present from birth,one with total trisomy 13 due to isochromosome (13q), and one with partial trisomy 13.

A cytogenetic re-evaluation at 9 years of age brought to light in skin fibroblasts a third cell line, par-tially monosomic for chromosome 13. The derivatives (13) present in the three cell lines were character-ized through fluorescence in situ hybridization (FISH) experiments with suitable probes; the resultssuggested a sequence of rearrangements which beginning from an isochromosome (13q) could have ledto the other two derivatives. We report the clinical data at birth and at the age of 12; at this age pigmentarylesions with phylloid pattern were noted. Cytogenetic findings of the chromosomal analyses on differenttissues, including skin fibroblasts from differently pigmented areas, are also reported.� 2008 Elsevier Masson SAS. All rights reserved.

Keywords: Patau syndrome; Trisomy 13; Mosaicism; FISH; Phylloid hypomelanosis

* Corresponding author. Tel.: þ39 079 228534; fax: þ39 079 228520.

E-mail address: [email protected] (G. Fogu).

1769-7212/$ - see front matter � 2008 Elsevier Masson SAS. All rights reserved.

doi:10.1016/j.ejmg.2008.03.004

mailto:[email protected]

http://www.elsevier.com/locate/ejmg

304 G. Fogu et al. / European Journal of Medical Genetics 51 (2008) 303e314

1. Introduction

Trisomy 13, or Patau syndrome [14], represents the third autosomic trisomy in order of fre-quency, after trisomy 21 (Down syndrome) and trisomy 18 (Edwards syndrome), with a preva-lence at birth estimated as between 1:12,000 and 1:29,000 [5,9]. Among the autosomictrisomies compatible with postnatal life, trisomy 13 is certainly the most severe as to congenitaldefects, psychomotor delay, mental retardation and life expectancy [1,2]. Magenis et al. [12], intheir study on 172 patients with full trisomy 13, found a death rate of 28% within the first week,44% within the first month, and 86% in the first year. Survivals beyond the first year of life areunusual, and beyond the first decade are exceptional, only seven patients over 10 being reportedto date [11,16,17,20e22], three of which over 18 [17,20,21]. The oldest patient so far reportedis an adult of 32 years of age [21]. In this work we describe a patient with Patau syndrome bornin 1995 and still living, in whom an unusual mosaic is present, including three cell lines withdifferent rearrangements involving one chromosome 13.

2. Case report

The patient, a 12-year-old girl, was the second child born to non-consanguineous, healthyparents when the mother was 23 and the father 26 years old. The first daughter was normaland the family history was unremarkable.

The pregnancy was remarkable for a reduction in foetal motility and a failure to progressfrom the 29th week. The infant was delivered at 32 weeks of gestation by caesarean section.Birth weight was1420 g (�3SD), length 37 cm (�3SD), and head circumference 27 cm(�3SD). APGAR score was 8 at 1 min.

She was admitted to the intensive neonatology unit due to respiratory distress, generalizedincrease in muscle tone and abnormal crying.

The newborn examination revealed multiple dysmorphic features with major somatic abnor-malities, including microcephaly, dolichocephalous cranium, high sloping forehead, flat hae-mangioma of the scalp, prominent coronal and occipital sutures, low set ears, hypertelorism,long eyelashes, downslanting palpebral fissures, flat nasal bridge, long smooth philtrum, micro-gnathia, wide mouth, thin upper lip, short lingual fraenulum, and high arched palate. Defor-mities of hands, feet and body were associated to the facial deformities as well as short neck(Fig. 1A), pectus excavatum, kyphoscoliosis, cubitus valgus, overlapping and flexed fingers,camptodactyly of the third and fourth fingers, hypoplasia of distal phalange of the fifth fingerof the right hand, clubfoot, adduct metatarsus (Fig. 1C), allux valgus, and overlapping toes.

Associated ophthalmic, cardiovascular, and urogenital defects have been identified: pale op-tical disc and retinal dysplasia, ostium secundum, interventricular defect, patent Botallo’s duct,calico-pyelic ectasia, and anterior anus.

Global developmental delay was noticed from early infancy. She began babbling at 2 yearsof age, smiling and speaking at 3 years, sitting at 2 years, standing up with help at 5 years andcrawling at 12 years. She has never trained toilet.

Severe feeding and chewing difficulties and failure to thrive persisted despite normal dentition.The patient takes Niaprazina because of significant disorder of sleep/wake cycle and inabil-

ity to fall asleep or maintain sleep.At 1 year she was treated with Valproate because of generalized seizures. EEG revealed ab-

normalities of background activity without paroxysmal discharges. Neurological examinationshowed poor motility and muscular hypertonia both in the lower and upper limbs.

Fig. 1. Phenotypic aspects of the patient. The infant at birth (A) and at 12 years (B); pigmentary mosaicism on the back

(C); feet (D). Linear white streaks are evident on both feet.

305G. Fogu et al. / European Journal of Medical Genetics 51 (2008) 303e314

At some time she began to suffer from frequent urinary infections always treated with an-tibiotic therapies.

Neurological examination at 2 years revealed spastic quadriplegia; at this age she starteda program of physical and cognitive therapy.

At 11 years the patient had a single menstrual cycle without physical signs of puberty.At 12 years she was admitted at Institute of Child Neuropsychiatry of Sassari University. At

examination, her weight was 24.6 kg (�3SD), length was 135 cm (�3SD) and head circumfer-ence was 48 cm (�3SD). Severe kyphosis and scoliosis, joints’ ankylosis most pronounced inthe lower limbs, associated to the dysmorphic features and malformations above delineatedwere also noticed. Respiratory insufficiency due to thoracic deformity was a severe problem. Neu-rological examination demonstrated significative hypotrophy of muscles and severe spastic quad-riplegia predominantly right-sided. The patient spoke sometimes few words to communicate,didn’t stand nor walk alone. She was already taking Valproate and was seizures free. Her intellec-tual capacities were severely compromised. She was not able to perform standard intellectual tests.According to the Vineland scales for adaptive behaviour, she results as a child of 18 months of age,motor and daily skills being more compromised than communication and socialisation skills.


Magnetic resonance imaging showed periventricular leukomalacia probably due to hypoxiceischemic insult, mild hypoplasia of corpus callosum, enlarged cisterna magna, and small heter-otopias in the subcortical white matter of the right cerebral hemisphere. Abnormal position ofthe first and second cervical vertebra was also observed. This MRI was similar to that performedwhen the patient was 2 years old. Nerve conduction showed motor and sensor neuropathy.

The results of other instrumental examinations as EEG, EKG, echocardiography, and ultra-sound of kidneys and bladder were normal.

2.1. Cutaneous symptomatology

From the age of 1 the patient started to show white cutaneous streaks following the lines ofBlaschko, according to the classical hypomelanosis of Ito, meeting with hyperchromic spots ofseveral centimetres in size. These lesions evolved with the progressive appearance on the backof various oval or roundish hypopigmented patches, irregular areas of a white coffee colour andhypopigmented streaks in a V formation (Fig. 1C). Hypopigmented linear streaks and hypopig-mented oval spots are also present on the internal side of the lower limbs (Fig. 1D). The currentappearance seems to agree with the form of pigmentary dysplasia denominated phylloid hypo-melanosis, classified as type 3 by Happle [6].

3. Materials and methods

3.1. Cytogenetics

Routine cytogenetic analyses in QFQ banding were carried out at birth on peripherallymphocytes, cutaneous fibroblasts and lymphoblastoid cells; at the age of 9 a cytogeneticre-evaluation was performed on peripheral lymphocytes and on cutaneous fibroblasts fromtwo different skin biopsies, coming from differently pigmented areas, one hyperpigmentedand the other seemingly normal. Routine cytogenetic analyses of the parents were carriedout on peripheral lymphocytes.

3.2. Molecular cytogenetics

FISH experiments were performed with the following commercial DNA probes: whole chro-mosome painting probe (13) (Vysis) and LSI 13 (RB-1) (Vysis) according to the protocols sug-gested by the manufacturers. The BAC probes used in this study, selected for theirchromosomal localization (UCSC, March 2006; http://genome.ucsc.edu/cgi-bin/hgGateway)and kindly supplied by Professor Mariano Rocchi (Institute of Genetics, Bari, Italy), wereprepared according to the protocols of the Sanger Centre Institute for bacterial cultures,DNA extraction and probe labelling with biotin-16-dUTP or digoxigenin-11-dUTP. Hybridiza-tion, post-hybridization washings and detection were carried out according to standard proce-dures. The FISH slides, stained with 40,6-diamidino-2-phenylindole (DAPI), were observedwith Olympus BX61 epifluorescence microscope equipped with specific filters.

3.3. Molecular analysis

The genomic DNA of the patient and parents was extracted from blood following the stan-dard salting-out procedures. Thirteen microsatellite markers on chromosome 13 (D13S175,

http://genome.ucsc.edu/cgi-bin/hgGateway


D13S217, D13S218, D13S263, D13S153, D13S156, D13S170, D13S265, D13S159, D13S158,D13S173, D13S1265, and D13S285) were genotyped and analysed. These markers were part ofthe whole genome linkage commercial panels from Applied Biosystems (ABI PRISM LinkageMapping Sets V2.5). Microsatellites were first amplified by PCR using fluorescently labelledprimers in a reaction volume of 7.5 ml (containing 5.25 pmol of each primer, 1.5 nmol ofeach of the four deoxynucleotide triphosphates and 0.2 units of AmpliTaq Gold polymerase(Applied Biosystems) in a 2.5 mM MgCl2 buffer). PCRs were performed in ABI thermal cy-clers using a standard file for all markers: 12 min at 96 �C (30 s at 94 �C/30 s at 55 �C/30 sat 72 �C)� 10 times, (30 s at 89 �C/30 s at 55 �C/30 s at 72 �C)� 20 times, 10 min at 72 �C,15 �C ad infinitum. PCR was performed separately for each microsatellite marker, and thenpooled in panels. PCR products were then separated on a polyacrylamide polymer usinga 3100 ABI DNA capillary sequencer (Applied Biosystems). After electrophoresis separation,the PCR fragments were sized and genotyped using appropriate softwares. Alleles at each mi-crosatellite were then given a numerical value (1, 2, 3, and 4) starting with the allele with thelowest number of base pairs.

4. Results

4.1. Standard cytogenetics

As reported in Table 1, at birth two cell lines were present, where a normal chromosome 13was replaced in one by a derivative (13), interpreted at the time as rob(13;13)(q10;q10), laterfound to be isochromosome (13q) and in the other by a submetacentric derivative (13), witha shorter arm apparently extended from 13q14 to 13qter, which could thus be described as fol-lows: der(13)(13qter/cen::13q14/qter) (Fig. 2A and B). For simplicity, this chromosomehereafter will be referred to as large der(13). The reciprocal proportion of the two cell lines,with i(13q) and large der(13), respectively, was almost the same in the lymphoblasts, whereasin peripheral lymphocytes the cells with i(13q) were prevalent, with a ratio of the two cell typesof 30:10. On the contrary, in the cutaneous fibroblasts the cell line with large der(13) waslargely predominant, with a ratio of the two cell types of 131:18. No normal cells were foundin any of the tissues examined. The parents both had normal chromosomes.

At the age of 9 a routine analysis on peripheral lymphocytes confirmed the result alreadyseen at birth, while in the cutaneous fibroblasts coming from the two distinct skin biopsies

Table 1

Percentage distribution of the three cell lines in different tissues examined at different ages

Tissue Age Total cells Iso(13q) Large der(13) Small der(13)

Lymphoblasts Birth 80 41 (51%) 39 (49%) n.d.

Lymphocytes Birth 40 30 (75%) 10 (25%) n.d.

9 years 116 86 (74.14%) 30 (25.86%) n.d.

12 years 120 90 (75%) 30 (25%) n.d.

Skin fibroblasts Birth 149 18 (12%) 131 (88%) n.d.

9 years (Norm.a) 70 n.d. 50 (71%) 20 (29%)

9 years (Hyperpig.b) 61 n.d. 47 (77%) 14 (23%)

n.d., not detected.a Normal skin.b Hyperpigmented skin.

Fig. 2. Cut-out of normal (left) and derivative (right) chromosomes (13) in QFQ banding. (A) Isochromosome (13q);

(B) large der(13); and (C) small der(13).


the cell line with i(13q) seemed to have disappeared, while the cell line with the large der(13)was still present, together with a new cell line, where a normal chromosome 13 was replaced bya tiny submetacentric chromosome, interpreted as der(13)(13q11/cen/13q13), hereafter in-dicated as small der(13) (Fig. 2C). The reciprocal proportion of the two cell types was almostthe same in the two cutaneous samples, in both being prevalent the cell line with large der(13),with a ratio of 50:20 in the normal skin and 47:14 in the hyperpigmented skin.

4.2. Molecular cytogenetics

All the three derivatives (13) showed complete painting with the whole chromosome paint-ing probe of chromosome 13; the LSI 13 (RB-1) probe, mapping to 13q14.2, gave a singleFISH signal on the normal chromosome 13, two FISH signals (on both arms) both on thei(13q) and on the large der(13) and no signals on the small der(13).

Further FISH analyses were carried out with the BAC probes shown in Fig. 3; the isochro-mosome was positive on both arms for all the probes tested (not shown in figure), while thelarge and the small derivatives (13) showed a pattern of FISH signals specular to one another.

According to FISH results one of the breakpoints from which the large der(13) and the smallder(13) both could originate from the i(13q) was found inside the BAC clone RP11-186J16 in13q13.3; a second breakpoint was proximal to the probe RP11-71I1, mapping in 13q12.11.

We can therefore characterize as follows the three cell lines present in our patient: the cellline with i(13q) is totally trisomic for chromosome 13; the cell line with the large der(13) istrisomic for 13q13.3/qter (w75 terminal Mb) and the cell line with the small der(13) ismonosomic for the same region. The patient’s karyotype can be indicated as: 46,XX,i(13q)/46,XX,der(13)(13qter/cen::13q13.3/qter)/46,XX,der(13)(13q11/cen/13q13.3).

4.3. Molecular analysis

The analysis of the microsatellite polymorphisms reported in Table 2 showed the presence inour patient of only two alleles, one of maternal, and one of paternal origin at all the loci tested,which spans the whole long arm of chromosome 13. This result leads us to hold that the pre-sumed der(13) rob(13;13)(q10;q10) is in all probability an isochromosome (13q).

Fig. 3. List of BAC probes used and FISH results on large and small derivatives (13). In bold the BAC clone identified as

one of the breakpoints on i(13q).

Table 2

Microsatellite results

Locus Localization Father Patienta Mother

D13S175 13q12.11 1 1 1 1 1 1

D13S217 13q12.3 1 2 2 2 2 3

D13S218 13q13.3 1 2 1 3 2 3

D13S263 13q14.1 1 4 4 3 2 3

D13S153 13q14.2 2 3 2 1 1 4

D13S156 13q22.1 2 3 2 1 1 2

D13S170 13q31.1 2 3 2 4 1 4

D13S265 13q31.3 1 3 3 3 2 3

D13S159 13q32.2 3 4 4 1 2 1

D13S158 13q33.1 1 3 1 3 2 3

D13S173 13q33.3 1 2 2 1 1 3

D13S265 13q33.3 1 3 3 1 1 2

D13S285 13q34 1 2 2 1 1 3

a Proband: two alleles at all loci tested; paternal allele (left) and maternal allele (right).



5. Discussion

Chromosomal mosaics made up of cell lines with different structural rearrangements involv-ing the same chromosome are unusual, and their origin often remains obscure. A case similar toours was reported by Reardon et al. [16] in an 11-year-old patient, in whom two cell lines werepresent, one with an apparent rob(13;13)(q10;q10) and the other with a submetacentric der(13),seemingly the same as the large der(13) of our case.

The authors suggested three different possible mechanisms which could explain the origin ofthe two cell lines, but none of the formulated hypotheses had cytogenetic evidence. On thecontrary, in our case a third cell line is present, which would explain the origin of the unusualmosaic, starting from a cell with isochromosome (13q). This cell is most likely the zygote,since no normal cells were found in any of the cytogenetic analyses performed at differentages of the patient and on different tissues.

Our hypothesis is that in one of the post-fertilization divisions two breakages may have oc-curred in the isochromosome at the stage of two chromatids, in one arm at q11 band and in theother at q13.3; erroneous rejoinings would lead to both large and small derivatives, with loss ofacentric fragments (Fig. 4).

Thus two offspring cells would be formed, originating two distinct cell lines. The FISH re-sults seem to confirm our hypothesis, as the probes which give positive signals on the largeder(13) come up negative on the small der(13), and vice versa, which is just the expected result.

The persistence of the cell line with i(13q), still present in blood lymphocytes, implies thatthis rearrangement occurred in a late post-zygotic cell division.

Therefore in our patient, besides the two cell lines totally or partially trisomic, a third cellline is present, almost entirely monosomic for chromosome 13, which could possibly play somerole in mitigating the clinical severity of the classical Patau syndrome.

Fig. 4. Hypothetic origin of both large and small derivatives (13) from an isochromosome (13q). (A) Two breaks at q11

and q13.3 of the opposite arms of an i(13q), with loss of acentric fragments; (B) correct and erroneous rejoining of

residual fragments; and (C) large der(13) and small der(13).

Table 3

Comparison of clinical features in seven long-surviving patients with Patau syndrome and in our patient (from Zoll et al. [22], modified)

Trisomy 13

common

symptoms

Boy, 11 ya Girl, 19 ya Boy, 10 yb Adult,

male,

22 yc

Girl, 11 yd Adult,

female, 32 yeGirl, 12 yf Present case,

girl, 12 y

Birth time Preterm Preterm At term At term At term Preterm Preterm n.m. Preterm

Birth weight Mean

2600 g

2370 g 2760 g 2610 g 3400 g 1560 g n.m. 2540 g 1420 g

Neonatal asphyxia (þ) � þ � � þ � � �Pregnancy (Complicated) Uncomplicated Uncomplicated Uncomplicated n.m. Complicated n.m. Uncomplicated Complicated

Brain

Microcephaly þ þ þ þ þ þ þ n.m. þHoloprosencephaly þ � � � � � � � �

Eyes

Microphthalmia þ þ þ þ þ Sunken eyes þ þ �Coloboma/cataracts þ þ þ þ n.m. � þ þ �

Ears

Hearing loss (þ) þ � þ � þ þ � �Low-set ears þ n.m. � n.m. n.m. þ n.m. þ �Dysmorphic ears þ þ þ þ n.m. þ n.m. þ þ

Head and face

Scalp defect þ n.m. n.m. n.m. n.m. þ n.m. � �Sloping forehead þ þ þ þ þ þ n.m. n.m. þBroad, flat nose þ þ þ þ n.m. þ Prominent n.m. þCleft lip and or palate þ � � þ � � � � �Highly arched palate þ þ þ n. m. þ þ n.m. n.m. þProtruding lower lip (þ) � þ � n.m. þ n.m. þ �

Heart defects þ þ Dextrocardia Dextrocardia n.m. � Dextrocardia � þRenal malformations þ � � � n.m. þ n.m. � �Genital anomalies (þ) þ þ þ þ � � þ �Limb anomalies

Hexadactily þ þ þ þ � � � � �Flexion deformity of fingers þ þ þ þ þ þ � n.m. þClub feet, rocker-bottom feet þ þ þ n.m. þ � � n.m þJoint contractures (þ) þ þ n.m. þ þ þ n.m. þOthers limb anomalies þ þ þ þ

(continued on next page)

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Table 3 (continued )

Trisomy 13

common

symptoms

Boy, 11 ya Girl, 19 ya Boy, 10 yb Adult,

male,

22 yc

Girl, 11 yd Adult,

female, 32 yeGirl, 12 yf Present case,

girl, 12 y

Kyphosis, scoliosis (þ) þ þ n.m. n.m. � n.m. n.m þMental retardation þ þ þ þ þ þ þ þ þSeizures þ þ þ n.m. þ þ þ � þFailure to thrive þ þ þ n.m. n.m. þ þ n.m. �Recurrent infections (þ) þ þ þ þ þ þ þ þCytogenetics Lþ Lþ Lþ Lþ:

full/partial

trisomy 13

Lþ Lþ Lþ Lþ Lþ:

full/partial

trisomy 13

SKþ SKþ SKþ:

full/partial

trisomy 13

SKþ:

mos?

SKþ SKþ SKþ:

full/partial

trisomy/

partial

monosomy

13

þ, symptom present; �, symptom not present; (), not obligatory; n.m., not mentioned.

Lþ, SKþ e trisomy 13 present in lymphocytes and skin fibroblasts; mos, mosaic trisomy 13.a Redheendran et al. [17].b Reardon et al. [16].c Singh [20].d Zoll et al. [22].e Tunka et al. [21].f Iliopoulos et al. [11].

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A possible complementation at tissutal level of the two opposite imbalances (trisomy andmonosomy), suggested by some authors [3,8], may be an attractive hypothesis, but nowadaysthere is no experimental evidence for this. On the other hand the composition of the mosaicin the fibroblasts, with a prevalence of the partially trisomic line, may be on its own sufficientto justify the mild phenotype in our patient.

The chromosomal mosaicism, together with translocation trisomy, could also account for herlong survival. Longer survivals, compared with cases of classical, free, full trisomy 13, have infact been noted by several authors in patients with translocations and mosaics [3,12,17]; nev-ertheless, out of seven patients over the age of 10 to date reported, four had free and homoge-neous trisomy, found both in blood lymphocytes and cutaneous fibroblasts, so with a reasonableexclusion of mosaics [17 (patient 1), 20e22], two had free and homogeneous trisomy ascer-tained in peripheral lymphocytes only [11,17 (patient 2)] and only one, the already cited patientreported by Reardon et al. [16], had translocation trisomy in mosaic in peripheral lymphocytes.

A comparison of the phenotype of these long-surviving patients, including the present case(Table 3), highlights the lack in all of severe cardiac and cerebral malformations, in particularthe absence of holoprosencephaly, which seems to affect unfavourably the prognosis ‘‘quoadvitam’’ [4].

An interesting feature of our patient is represented by pigmentary anomalies, resembling intheir current aspect the so-called phylloid hypomelanosis. This is a form of pigmentary dyspla-sia, classified by Happle [6] as type 3, which is characterized by variable combinations of hy-pochromic and hyperchromic lesions arranged in such a way as to resemble the leaves ofa begonia. This peculiar form of pigmentary mosaicism seems to be closely related to mosaictrisomy 13; indeed among six patients with phylloid hypomelanosis collected in a review byHapple [7], five resulted as having anomalies involving one chromosome 13 in peripheral lym-phocytes [10,13,15,18,19], and in four of these a condition of mosaicism was highlighted in thecutaneous fibroblasts [13,18,19]. Cytogenetic data from skin biopsies coming from differentlypigmented areas, available in two cases [10,13], showed in both patients the same proportion ofthe cell lines making up the mosaic in all the samples examined, therefore suggesting that noneof the cell lines could be mostly assigned to specific pigmentary areas. The cytogenetic resultsin our patient seem to agree with this, so from this point of view the present report is a usefulcontribution.

To conclude, we feel that our work, with the report of an unusual cytogenetic variant of theclassical Patau syndrome, could contribute to explain other cases of chromosomal mosaicismsof uncertain origin. Also, the clinical description of our patient may help to illustrate some clin-ical aspects of Patau syndrome that can only be observed in long-surviving patients, such as thecutaneous symptomatology.

What is more, our experience suggests that it is suitable to examine more than one tissue notonly in cases of ascertained mosaics, but also when some discrepancy is observed between cy-togenetics and phenotype, such as an unexpected long survival in subjects with chromosomalanomalies that are known to be cause of early death.

Acknowledgements

We wish to thank the family of our patient for having authorized this research and ProfessorMariano Rocchi, General Biology, University of Bari, Italy, for the supply of BAC/PAC probesused in this work.


References

[1] B.J. Baty, B.L. Blackburn, J.C. Carey, Natural history of trisomy 18 and trisomy 13: I. Growth, physical assess-

ment, medical histories, survival, and recurrence risk, Am. J. Med. Genet. 49 (1994) 175e188.

[2] B.J. Baty, L.B. Jorde, B.L. Blackburn, J.C. Carey, Natural history of trisomy 18 and trisomy 13: II. Psychomotor

development, Am. J. Med. Genet. 49 (1994) 189e194.

[3] M. Gentile, A.L. Buonadonna, F. Cariola, P. Fiorente, M.C. Valenzano, G. Guanti, Molecular and cytogenetic char-

acterisation of an unusual case of partial trisomy/partial monosomy 13 mosaicism: 46,XX,r(13)(p11q14)/

46,XX,der(13)t(13;13)(q10;q14), J. Med. Genet. 36 (1) (1999) 77e82.

[4] M. Goel, R. Rathore, Trisomy 13 (Patau syndrome), Indian J. Pediatr. 37 (2000) 1140.

[5] H. Goldstein, K.G. Nielsen, Rates and survival of individuals with trisomy 13 and 18. Data from a 10-year period

in Denmark, Clin. Genet. 34 (6) (1988) 366e372.

[6] R. Happle, Mosaicism in human skin: understanding the patterns and mechanism, Arch. Dermatol. 129 (1993)

1460e1470.

[7] R. Happle, Phylloid hypomelanosis is closely related to mosaic trisomy 13, Eur. J. Dermatol. 10 (7) (2000)

511e512.

[8] M.E. Hodes, J. Cole, C.G. Palmer, T. Reed, Clinical experience with trisomies 18 and 13, J. Med. Genet. 15 (1)

(1978) 48e60.

[9] E.B. Hook, Rates of 47, þ13 and 46 translocation D/13 Patau syndrome in live births and comparison with rates in

fetal death and at amniocentesis, Am. J. Hum. Genet. 32 (6) (1980) 849e858.

[10] D. Horn, M. Rommeck, D. Sommer, H. Korner, Phylloid pigmentary pattern with mosaic trisomy 13, Pediatr. Der-

matol. 14 (4) (1997) 278e280.

[11] D. Iliopoulos, E. Sekerly, G. Vassiliou, V. Sidiroupulos, A. Topalidis, D. Dimopoulou, N. Voyiatzis, Patau syn-

drome with a long survival (146 months): a clinical report and review of literature, Am. J. Med. Genet. A 140

(2006) 92e93.

[12] R.E. Magenis, F. Hecht, S. Milham Jr., Trisomy 13 (D1) syndrome: studies on prenatal age, sex ratio, and survival,

J. Pediatr. 73 (2) (1968) 222e228.

[13] H. Ohashi, M. Tsukahara, I. Murano, K. Naritomi, K. Nishioka, S. Miyake, T. Kajii, Pigmentary dysplasias and

chromosomal mosaicism: report of 9 cases, Am. J. Med. Genet. 43 (4) (1992) 716e721.

[14] K. Patau, D.W. Smith, E. Therman, S.L. Inhorn, H.P. Wagner, Multiple congenital anomaly caused by an extra

autosome, Lancet 1 (1960) 790e793.

[15] T. Pillay, W.S. Winship, P.K. Ramdial, Pigmentary abnormality in trisomy of chromosome 13, Clin. Dysmorphol.

7 (1998) 191e194.

[16] P.C. Reardon, R.M. Greenstein, R.O. Howard, E.K. Gianacopoulos, W.R. Breg, Unusual mosaicism of de novo

structural abnormalities and ocular anomalies in a male with trisomy 13 syndrome, Am. J. Med. Genet. 10

(1981) 113e118.

[17] R. Redheendran, R.L. Neu, R.M. Bannermann, Long survival in trisomy 13 syndrome: 21 cases including pro-

longed survival in two patients 11 and 19 years old, Am. J. Med. Genet. 8 (1981) 167e172.

[18] T. Ribeiro Noce, J.M. de Pina-Neto, R. Halle, Phylloid pattern of pigmentary disturbance in a case of complex

mosaicism, Am. J. Med. Genet. 98 (2001) 145e147.

[19] C. Schepis, P. Failla, M. Siragusa, C. Romano, An additional case of molecular phylloid mosaicism, Dermatology

202 (2001) 73.

[20] K.S. Singh, Trisomy 13 (Patau’s syndrome): a rare case of survival into adulthood, J. Ment. Defic. Res. 34 (1990)

91e93.

[21] Y. Tunka, J.S. Kadandale, E.K. Pivnick, Long term survival in Patau syndrome, Clin. Dysmorphol 10 (2001)

149e150.

[22] B. Zoll, J. Wolf, D. Lensing-Hebben, M. Pruggmayer, B. Thorpe, Trisomy 13 (Patau syndrome) with an 11-years

survival, Clin. Genet. 43 (1993) 46e50.

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