Maria Antonietta Serafina Moro

Patau syndrome with long survival in a case of unusual mosaic trisomy 13.

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, partially monosomic for chromosome 13. The derivatives (13) present in the three cell lines were characterized through fluorescence in situ hybridization (FISH) experiments with suitable probes; the results suggested a sequence of rearrangements which beginning from an isochromosome (13q) could have led to the other two derivatives. We report the clinical data at birth and at the age of 12; at this age pigmentary lesions with phylloid pattern were noted. Cytogenetic findings of the chromosomal analyses on different tissues, including skin fibroblasts from differently pigmented areas, are also reported.

Unbalanced 1q Whole-Arm Translocation Resulting in der(14)t(1;14)(q11-12;p11) in Myelodysplastic Syndrome

Unbalanced whole-arm translocations (WATs) of the long arm of chromosome 1, resulting in complete trisomy 1q, are chromosomal abnormalities detectable in both solid tumors and hematologic neoplasms. Among the WATs of 1q to acrocentric chromosomes, a few patients with der(1;15) described as a dicentric chromosome have been reported so far, whereas cases of der(1;14) are much rarer. We report on a case of der(1;14) detected as single anomaly in a patient with myelodysplastic syndrome. The aim of our work was to investigate the breakpoints of the (1;14) translocation leading to the der(1;14). Fluorescence in situ hybridization (FISH) experiments have been performed on chromosome preparations from bone marrow aspirate, using specific centromeric probes of both chromosomes, as well as a probe mapping to 1q11 band. FISH results showed that in our patient the derivative chromosome was monocentric with a unique centromere derived from chromosome 14. The breakpoints of the translocation were located in the short arm of chromosome 14 and in the long arm of chromosome 1, between the alphoid D1Z5 and the satellite II domains. The 1q breakpoint was within the pericentromeric region of chromosome 1, which is notoriously an unstable chromosomal region, involved in different chromosomal rearrangements.

Partial trisomy of the long arm of chromosome 1: Prenatal diagnosis, clinical evaluation and cytogenetic findings. Case report and review of the literature

Partial trisomy of the long arm of chromosome 1 is a relatively rare cytogenetic anomaly. Its phenotype has still not been completely defined, because of the cytogenetic heterogeneity of the cases so far described. We report a prenatal case of partial 1q trisomy associated with partial monosomy 4q, secondary to balanced maternal translocation t(1;4). The trisomic segment extended from 1q31.1 to qter and the monosomy 4q was from 4q35.2 to qter. The phenotypic anomalies found by post‐mortem and autopsy examinations were compared with those of similar cases reported in the literature. We performed standard cytogenetics and fluorescence in situ hybridization. Cerebral ventriculomegaly, present in our case, seemed to be a constant feature in partial 1q trisomies, so this cerebral malformation could be considered as the main echographic marker for this chromosomal imbalance and trisomy 1q should be added to the list of chromosomal abnormalities associated with ventriculomegaly.

Prenatal diagnosis and molecular cytogenetic characterisation of a de novo 18p deletion

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Morphological findings in malformed fetuses with normal karyotype

In our Department morphological findings on fetuses from therapeutic interruption of pregnancy or spontaneous abortion are performed since ten years in order to correlate the ultrasound and/or chromosomic diagnosis with a real presence of malformations. The fetopathologic examination generally agrees with the chromosomal diagnosis, while in several cases it is possible to find malformations also in presence of a normal karyotype (Gitz, 2011). In our experience over the past 5 years we have found that 17 fetuses with a normal karyotype showed different heterogeneous ultrasound malformations. Only in 2 cases the fetuses died in uterus (17th and 22nd weeks of gestation), the other cases, aged between 14th and 23rd weeks of gestation, went from voluntary abortions. In 7 cases the karyotype was defined by amniocentesis while in the remaining 10 was determined by fetal fibroblasts culture; in only 30% of the observed cases the couple had carried out a genetic evaluation. External malformations were present in 16 fetuses, often related to the face (such as micrognathia, low-set of ears, flattened nasal bridge, cleft lip) or limb (short, curved, stubby) of spine (spina bifida) or genitalia (hypospadias). Malformations of internal organs were present in 10 cases, often affecting the cardiovascular system (complex heart defects and abnormal origin of the greath vessels), and nervous system (meningocele, agenesia of the corpus callosum, ventricular dilatation and Arnold-Chiari malformation); less frequent were malformations of other systems (digestive, respiratory and urinary). There was a single case of situs viscerum inversus associated with complex cardiac malformations and atresia of the bucco-pharyngeal membrane. These results indicate that the fetal morphological study is useful not only to confirm but often to supplement and complete the ultrasound data. Moreover genetic evaluation, utilizing fetopatholgical study, may have an important role in defining the diagnostic and clinical procedure, especially in relapses with malformed fetus and normal karyotype.

Morphological examination of a preterm neonate with atypical Pallister-Killian syndrome

Pallister-Killian syndrome (PKS) is a rare genetic disorder which is cytogenetically characterized by a tissue limited mosaic distribution of isochromosome 12p (tetrasomy 12p). This chromosomal anomaly may be detected in fibroblasts and in bone marrow cells, in amniocytes, chorionic villus and other foetal tissues, whereas it is absent in peripheral lymphocytes. The percentage of abnormal cells in fibroblasts decreases with the ageing, so adult patients may be undiagnosed.We report on a preterm male neonate of 1320 gr of weight, born at a gestational age of 29-30 weeks. He had severe respiratory distress and died after a few hours, in spite of intensive resuscitation. The external examination showed a disproportionate large face and low-set ears, limbs of normal length, with normal hands and feet, normal genitalia. At the autopsic examination all the thoracic, abdominal and pelvic organs were normal, the palate showed a schisis in the posterior side of the arch; the external appearance of the brain was normal, with hyperaemic pial membrane. The cytogenetic analysis on skin fibroblasts showed the presence of a supernumerary metacentric chromosome, consistent with an isochromosome 12p. Subsequent interphasic FISH with a centromeric probe detected tetrasomy 12p in mosaic.The postnatal phenotype of PKS is quite severe and include coarse facies with a high forehead, sparce scalp hair, hypertelorism, broad nasal bridge, hypotonia, streaks of hypo-hyperpigmentation. Hydramnios, congenital diaphragmatic hernia and micromelia, of predominantly rhizomelic type are frequent echographic signs during the pregnancy. Hydrops fetalis, hygroma colli, increased nuchal translucency (INT), foetal overgrowth and ventriculomegaly are less frequently reported. In the present case no foetal malformations were evident during the pregnancy, and the facial dysmorphisms and congenital malformations described in PKS were absent at the morphological and autopsic examination of the newborn. This suggests that PKS could be suspected, and then verified on skin fibroblasts, even in absence of significant congenital malformations, mainly in dysmorphic patients cytogenetically normal at standard cytogenetics on peripheral lymphocytes.

18p deletion syndrome : foetal phenotype and cytogenetic characterization

Monosomy for the short arm of chromosome 18 is one of the most common autosomal deletion syndromes, with an estimated incidence of about 1:50000 live-born. The phenotype of this chromosome imbalance is greatly variable, often not evident at birth. In this communication we describe a case prenatally diagnosed of de novo 18p deletion.Amniocentesis was performed at 17 weeks of gestational age on a 39-year-old gravid. The family history was unremarkable and the pregnancy was uncomplicated. At the time of the amniocentesis the amniotic fluid alphafetoprotein level was slightly lower than normal. The pregnancy was terminated at 18 weeks, after the cytogenetic response. At the time the ultrasonographic examination showed reduced biparietal diameter and head circumference, normal limbs, normal thoracic, abdominal and pelvic organs. The external examination of the aborted foetus showed: weight 380 gr; ipsicephaly and nuchal oedema, no facial dysmorphic signs, normal ears, limbs of normal length, overlapping toes in the right foot. External genitalia were normal. At the autopsic examination the right lung showed four lobes; all the other organs of thorax, abdomen and pelvis were normal.Cytogenetic analysis of cultured amniocytes showed a de novo 18p deletion. FISH studies allowed us to define the foetal karyotype as: 46,XX, del(18)(p10pter).ish del(18)(tel18p-, dim D18Z1). The phenotypic spectrum of 18p- syndrome may include: round face, ptosis, flat and broad nasal bridge, wide mouth with short upper lip, small mandibles, irregular teeth and dental caries, large, protruding ears, often low and posteriorly rotated, short neck, pectus excavatum, kyphoscoliosis, hands and feet anomalies. The main malformations are holoprosencephaly (HPE), cardiac defects and genital anomalies. Growth retardation, psychomotor delay and mental insufficiency, often mild, are constant symptoms of the syndrome. The foetal phenotype is inconsistent, but the increased nuchal translucency (INT) seems to be a sonographic sign suggestive of this chromosomal abnormality. This further stress the importance of accurate morphological ultrasonographies, mainly in the second trimester, in order to prevent rare and oligosymptomatic chromosomal syndromes.