Contribution of 3D ultrasound and fetal face studies to the prenatal diagnosis of Pallister-Killian syndrome

Background.?Pallister-Killian syndrome (PKS) is a multiple malformation syndrome caused by a chromosomal abnormality in which the presence of four copies of the short arm of chromosome 12 results in severe mental retardation. Cytogenetic diagnosis is particularly difficult due to the specific tissue distribution of the abnormality. PKS may be suspected based on the prenatal ultrasound detection of polyhydramnios and diaphragmatic hernia, possibly associated with rhizomelic micromelia.

Method and results.?We report here a case of PKS in which the 3D ultrasound examination of facial features after prenatal PKS diagnosis showed signs suggestive of the syndrome.

Conclusion.?A detailed 3D examination of the fetal face may help to guide diagnosis, particularly when the only sign detected on ultrasound is polyhydramnios, as in the case reported here.     

Amniocentesis can be useful during the third trimester of pregnancy for antenatal diagnosis of Pallister-Killian syndrome: a case report

Pallister-Killian syndrome (PKS) is an extremely rare genetic disease characterized cytogenetically by tetrasomy 12p mosaicism. We recently encountered a case of maternal hydramnios associated with congenital diaphragm hernia according to the prenatal diagnosis. Prenatal diagnosis revealed a non-mosaic 47, XY, i(12)(p10) karyotype at amniocentesis of G-band and M-FISH analysis. We performed chromosomal analysis in both interphase and metaphase cells from a cord blood lymphocyte specimen. Mosaic tetrasomy of chromosome 12p was supported by G-banding or FISH analysis. When fetal observations are performed in detail using 2D/3D US, PKS may be diagnosed. In addition, it is effective to perform amniocentesis during the third trimester of pregnancy.     

Pallister-Killian syndrome: difficulties of prenatal diagnosis

The first prenatal diagnosis of Pallister-Killian syndrome (PKS) was reported by Gilgenkrantz et al. in1985. Since this report, about 60 prenatal cases have been reported but both sonographic and cytogenetic diagnoses remain difficult. Although ultrasound anomalies such as congenital diaphragmatic hernia, polyhydramnios and rhizomelic micromelia in association with fetal overgrowth are very suggestive of the syndrome, they are inconstant and they may even be absent. The mosaic distribution of the supernumerary isochromosome 12p greatly increases these difficulties. No prenatal cytogenetic technique is sensitive enough to ensure prenatal diagnosis and false-negative results have been described on fetal blood, chorionic villi and amniocentesis. We report here two prenatal cases of PKS which illustrate the great variability of the fetal phenotype. In reviewing the 63 reported cases, we attempt to determine ultrasound indicators of the syndrome and to define a cytogenetic strategy. In cases where ultrasound indicators are present, our proposal is first to perform chorionic villus or placental sampling and then amniocentesis when the first cytogenetic result is normal. Fetal blood sampling is the least indicated method because of the low frequency of the isochromosome in lymphocytes. In this cytogenetic strategy, fluorescent in situ hybridization (FISH) and especially interphase FISH on non-cultured cells increases the probability or identifying the isochromosome. A misdiagnosis remains possible when ultrasound is not contributory; the identification of new discriminating ultrasound indicators would be very helpful in this context.     

Prenatal diagnosis of Pallister-Killian syndrome in pregnancy with normal CVS result and abnormal ultrasound findings in the second trimester

Objective

To highlight importance of detailed ultrasound examination in fetuses with known normal karyotype (and micro-array result) from CVS. In case of markedly abnormal ultrasound result repeated karyotyping by amniocentesis should be considered. Sample should be analyzed by routine cytogenetic techniques, however also micro-array and targeted FISH should be added in order to achieve most accurate diagnosis.

Prenatal diagnosis of hypoplastic left ventricle

A case of prenatal diagnosis of hypoplastic left ventricle by means of echocardiography is presented. The method of detecting this syndrome is described and the importance of its prenatal diagnosis emphasized.     

Prenatal diagnosis of thrombocytopenia absent radius syndrome by ultrasound and cordocentesis

The prenatal diagnosis of thrombocytopenia absent radius (TAR) syndrome, utilizing ultrasound and cordocentesis, is described. To our knowledge, this represents the first prenatal diagnosis of this condition in an index case. The diagnostic evaluation of a fetus with upper extremity limb reduction defects is discussed.     

Diagnóstico prenatal en el segundo trimestre de displasia torácica asfixiante

A case of prenatal diagnosis of Jeune’s syndrome is described. Because the incidence of this syndrome is low, diagnosis in the 21st week of pregnancy is exceptional. Jeune’s syndrome, or asphyxiating thoracic dysplasia, is a skeletal dysplasia with autosomal recessive inheritance. Prenatal diagnosis can be established by ultrasonographic findings of a small thorax, short ribs, pelvic abnormalities, rhizomelic brachymelia, and renal and liver anomalies, among others. In the present case, the prenatal diagnosis was confirmed at necropsy.     

Prospective ultrasound diagnosis of Pallister-Killian syndrome in the second trimester of pregnancy: the importance of the fetal facial profile

The Pallister-Killian syndrome (PKS) represents a rare polymalformative complex characterized by a tissue-specific mosaic distribution of an additional isochromosome 12p and characterized by diaphragmatic hernia, rhizomelic limb shortening, facial anomalies and, rarely, acral hypoplasia. Since diaphragmatic hernia and acral hypoplasia can be also found in Fryns syndrome, the differential diagnosis between the two conditions depends on the demonstration of the 12p isochromosome by FISH. Prenatal diagnosis of PKS has been reported in cases submitted to karyotyping due to advanced maternal age or congenital anomalies detected on second trimester ultrasound. Among the ultrasound-detected malformations, little attention has been paid to facial anomalies. We describe a case in which PKS was prospectively suspected on the basis of the various anomalies detected at ultrasound, namely diaphragmatic hernia, rhizomelic limb shortening, and abnormal facial profile. The diagnosis was then confirmed by FISH on amniocytes and peripheral lymphocytes. In the present case, the disclosure of typical facial abnormalities significantly contributed to the differentiation between PKS and Fryns syndrome.     

Prenatal diagnosis of left ventricular false tendon

A case of prenatal diagnosis of left ventricular false tendon is reported. The in utero echographic features of false tendon are described, together with their differential diagnosis. The management of neonates with false tendons is described.     

Prenatal diagnosis of cloverleaf skull: watch the hands!

Pfeiffer syndrome is an extremely rare autosomal-dominant condition whose prenatal diagnosis has only been reported 6 times, mainly on the basis of a fetal cloverleaf skull deformity. Three types have been described, each with a different prognosis. This case report stresses the need to thoroughly analyze the fetus and particularly the fetal hands in case of prenatal observation of a cloverleaf skull. The discovery of characteristic hand abnormalities allowed the early prenatal detection of type 2 Pfeiffer syndrome in our patient.     

Fetus-in-fetu: two case reports

The objective of our study is to describe the sonographic findings of an extremely rare pathology. We therefore present two case reports of prenatal diagnosis of fetus-in-fetu (FIF) with a review of the literature. FIF is a benign disorder, unlike the teratoma with which often enter into the differential diagnosis, localized in most cases in the retroperitoneal space. Prenatal diagnosis is based mainly on ultrasound and radiological characteristics. The treatment of choice is surgical excision. The importance of prenatal diagnosis of fetus-in-fetu and the effect on subsequent management are described.     

Prenatal ultrasonic diagnosis of radial-ray aplasia and renal anomalies (acro-renal syndrome)

Prenatal ultrasonic diagnosis of a rare case of radial ray aplasia and crossed renal ectopy is described in an affected sibling of a family where the father and his son suffer from this rare syndrome. The prenatal diagnosis enabled early pregnancy termination.     

Prenatal ultrasonic diagnosis of arteriovenous malformation of the vein of Galen

A case of an arteriovenous malformation of the vein of Galen diagnosed in utero by ultrasound is presented. Upon review of the literature only two cases of prenatal sonographic diagnosis of this entity have been described. The prenatal sonographic features of this rare disorder are discussed.     

Prenatal diagnosis of Conradi's syndrome. Case report

A case is described of the diagnosis by ultrasound scanning during the second trimester of Conradi-Hünermann's syndrome (asymmetrical rhizomelic limb shortening or chondrodysplasia calcificans punctata). The prenatal diagnosis of limb shortening deformities is discussed.     

The importance of early prenatal diagnosis of thanatophoric dysplasia with respect to obstetric management

A case is described in which prenatal diagnosis of thanatophoric dysplasia was made in the second trimester of pregnancy by ultrasonography and radiography. Early diagnosis allowed elective abortion to be carried out, thus avoiding possible complications later in the pregnancy.     

Prenatal diagnosis and prenatal imaging features of fetal monosomy 1p36

Deletion of the distal end of the short arm of chromosome 1 (1p36) is thought to be a common terminal chromosomal deletion. However, few cases prospectively diagnosed prenatally have been reported. In this case, prenatal ultrasound at 21 weeks of gestation noted the fetus to have mild ventriculomegaly (Vhanterior = 11 mm and Vhposterior = 12 mm) and increased nuchal edema (6 mm). Maternal serum alpha-fetoprotein was normal unlike in a majority of previously described cases. The prenatal ultrasound features were further clarified with fetal MRI. Chromosome analysis following amniocentesis demonstrated a 1p36 deletion, which was confirmed by fluorescence in situ hybridization (FISH). The syndrome associated with 1p36 deletion is well described in infants and is characterized by typical facial features (prominent forehead, straight eyebrows. deep-set eyes, flat nasal bridge and a pointed chin). Other associated features are neurodevelopmental delay, seizures, cardiomyopathy and neurosensory hearing impairment. This case supplements our knowledge of the prenatal features of 1p36. Identification of this deletion by direct chromosomal analysis can be technically difficult and vigilance is required to improve diagnosis. FISH analysis is an important diagnostic adjunct where the diagnosis is suspected following classical G-banding techniques. However, in this chromosomal anomaly there remain few characteristic prenatal signs that are readily diagnosed with prenatal imaging.     

Humangenetische Diagnostik und Beratung

Most rare diseases have a genetic cause and their onset is in childhood, possibly even prenatally. The diagnosis of these disorders requires a high level of specialization and a well-coordinated multidisciplinary procedure. On the basis of three relatively frequent prenatal situations (radial aplasia, in this case with neural tube defect; polycystic kidneys; short bones), the stepwise diagnosis of a rare disease (Fanconi anemia, Meckel-Gruber syndrome, and achondrogenesis type 2, respectively) is described. The coordination of prenatal diagnostic investigations is up to the geneticist and requires nondirective and open-ended genetic counseling. Following the birth of an affected fetus or child, a thorough (photographic) documentation is crucial as well as the storage of appropriate samples after consultation of a geneticist. A targeted prenatal investigation in following pregnancies presupposes a confirmed diagnosis in the index patient. In addition, an etiological diagnosis plays an important part in the coping process of the parents.     

A new syndrome of myopathy with muscle spindle excess

Arthrogryposis may result from various neuromuscular or connective tissue disorders leading to in utero hypokinesia or akinesia and the prenatal development of joint contractures. We report the case of a preterm neonate born with arthrogryposis and flaccid quadriplegia that led to the diagnosis of myopathy with muscle spindle excess. The rare and unusual histopathologic abnormality associated with the myopathy illustrated in this case has been described in only three other cases in the medical literature. The concurrence of hypertrophic cardiomyopathy, arthrogryposis, and myopathy with muscle spindle excess suggests the presence of a newly described syndrome. This case clearly demonstrates that specific prenatal ultrasonographic findings combined with the presenting clinical manifestations should promptly raise the suspicion of a neuromuscular disorder.     

Prenatal sonographic diagnosis of multiple malformation in foetus--formation of ventral cleft and cephalocele (author's transl)

Reference is made to a case history of prenatal use of ultrasonography, in 34th week of pregnancy by which formation of a ventral cleft in conjunction with cephalocele was diagnosed. Additional methods to secure diagnosis are described and compared, including alpha-foetal protein evaluation and amniofoetography. Also discussed are obstetric consequences likely to result from possible prepartum diagnosis of such malformations.