Prenatal diagnosis and clinicopathologic examination of a case with diastematomyelia

Diastematomyelia is a rare form of spinal dysraphism. Here the spinal cord was split into two with a bony or cartilaginous spur, resulting in formation of two hemicords. The prenatal diagnosis of diastematomyelia is possible with ultrasonography. The unique finding is the appearance of echogenic focus within the spinal canal. This condition may not have any clinical sign during prenatal and early years of life but as the child grows, serious neurologic manifestations may occur, commonly termed the “tethered cord syndrome”. Here, we report a case of diastematomyelia in which a careful antenatal imaging was performed and postnatal pathologic examination confirmed the diagnosis.     

Prenatal diagnosis

With the leaping advances in knowledge of genetics, its applications in patient management are also increasing. Prenatal diagnosis is the most useful application as it offers prospective parents the assurance of having an unaffected child in situations of high recurrence risks. Pretest and post test counseling is an integral part of prenatal diagnosis. All Pediatricians and Obstetricians should be familiar with the basic prerequisites of prenatal screening/testing. Timely referral, preferably prepregnancy is important. There is more or less a consensus regarding offering prenatal diagnosis for lethal/chronic disabling or difficult/expensive to treat conditions. Ethical issues are already around regarding prenatal testing for disabilities like deafness and late onset disorders. The present communication is an effort to present the clinician’s perspective of prenatal diagnosis     

Prenatal diagnosis of haemophilia

Haemophilia A is a severe bleeding disorder caused by a deficiency in clotting factor vm (FVIII). It is an X-linked recessive bleeding disorder affecting one in 10,000 males. Prevalence of the haemophilia gene in the general population has increased recently due to advances in treatment, which has resulted in reproductive fitness among heamophiliacs. Patients suffering from this disease and their families are faced with problems relating to morbidity and mortality from the disease. These include a continual risk of uncontrolled bleeding, haemarthroses and subsequent arthropathy and above all, the genetic risk to progeny. Factor VIII gene is very large with 26 exons. Defects in this gene result in the deficiency of FVIII molecule. With the advent of recent advances in the molecular biology, it is possible to identify the multiple molecular defects such as point mutations, premature stop codons, deletions, and inversions etc in the FVIII gene in patients with haemophilia. Nowadays the use of polymerase chain reaction (PCR)-based linkage analysis and direct mutation detection in the chorionic villus sample obtained at 10–12 weeks of gestation has significantly improved the prenatal diagnosis of haemophilia.     

Prenatal diagnosis of galactosemia

The experience from three different European centres with the prenatal diagnosis of galactose-1-phosphate-uridyltransferase (GALT) deficiency is presented and the question whether or not there is a need for prenatal diagnosis of this disorder is discussed. Most prenatal diagnoses (n=50) have been performed by assay of GALT activity in cultured amniotic fluid cells. The assay used is reliable and clearly distinguishes homozygous affected fetuses (n=11; 0%–2.3% of mean control enzyme activity) from non-(homozygous)-affected fetuses. The GALT assay for cultured amniocytes was adapted to assay the enzyme directly in chorionic villi. The experience with chorionic villi comprises 23 cases with 5 affected fetuses (0%–4.2% of mean control enzyme activity). In 36 cases galactitol was determined in amniotic fluid supernatant by gas chromatography-mass spectrometry. This method also differentiated affected (n=11; galactitol 5.9–10.6 mol/l) and unaffected pregnancies (galactitol 0.23–1.6 mol/l) clearly and has the advantage of providing a result within a day or two after amniocentesis. Prenatal diagnosis of galactosemia is undertaken rarely and sometimes for the wrong reasons, but it should perhaps be considered more seriously until better methods of treatment are established.     

Prenatal diagnosis for paediatricians

In Ontario, approximately 140,000 women deliver newborn infants each year. Of these women, 60,000 to 70,000 have multiple marker screening, 10,000 undergo amniocentesis or chorion villus sampling and virtually all have at least one prenatal ultrasound. Multiple marker screening is not used in every province and territory; however, amniocentesis and prenatal ultrasound are used throughout Canada. Most paediatric patients will have been exposed to some form of prenatal diagnosis. If an abnormality is found prenatally, parents may have concerns to discuss with the paediatrician after the child is born. Likewise, if a child with a problem is born following a normal pregnancy, the parents will want to know why the problem was missed prenatally. Paediatricians should be aware of prenatal tests that have been performed to understand better their patients and their families.     

Prenatal diagnosis of brainstem anomalies

Prenatal diagnosis of brainstem anomalies is important due to the usually associated neurodevelopmental impairment and genetic implications. The extreme developmental changes that the brainstem and cerebellum undergo during fetal life pose a challenge for the characterization and definition of the different malformations.The present review aims to demonstrate the normal development of the fetal brainstem and to present the main features required for diagnosis of its anomalies according to available data in the medical literature.     

Prenatal diagnosis of unilateral hydrocephalus

We report a case of unilateral hydrocephalus diagnosed at 20 weeks' gestation, at which time marked facial and cranial asymmetry was present already. Brain mantle reconstitution was incomplete following vetriculo-peritoneal shunting, and the child has significant neurodevelopmental disability.     

Prenatal diagnosis of adrenal neuroblastoma

A right retroperitoneal mass with mixed solid and cystic pattern was detected sonographically in a fetus in the 36th week of pregnancy. After term delivery radiologic, sonographic, and CT studies confirmed the presence of a spherical, 5 × 4-cm mass above the right kidney with mixed echogenicity. At operation an enlarged adrenal gland containing hemorrhagic spaces was removed. Histological studies revealed adrenal neuroblastoma. This prenatal sonographic pattern was suggestive of neuroblastoma because it was identical to that of the only similar case reported so far. Prenatal detection is therefore possible and should be regarded as desirable since early diagnosis and treatment provide the best chances for cure. Offprint requests to: J. A. Tovar     

Prenatal diagnosis of inherited hemoglobinopathies

This paper reviews the methodology available to make prenatal diagnosis of inherited hemoglobinopathies by DNA analysis and the strategy to be used for the large scale application of this procedure to high-risk populations. The most straightforward approach for prenatal diagnosis is nowadays based on the analysis of DNA enzymatically amplified by the polymerase chain reaction (PCR). The mutations, produced by gross structural rearrangement of the DNA and those affecting a restriction recognition site, are directly detected by visualization following ethidium bromide staining of the electrophoretic pattern resulting from enzymatic digestion of amplified DNA. The remaining ones are detected by dot blot analysis with allelic specific oligonucleotide probes. Because in each population a limited number of specific Β-thalassemia mutations are prevalent, prenatal diagnosis by DNA analysis may be carried out by a population-specific strategy based on the amplification of those regions of the Β-globin genes containing the mutations most frequently occurring in each population followed by dot blot analysis with allelic specific oligonucleotide probes. This approach has the great advantage of being very simple, because radioactive probes are not necessary, very rapid, the results being obtained within 24 hours from sampling and very sensitive, only a limited amount of DNA in the order of 50 ng being necessary.     

Prenatal diagnosis of chylothorax]

Chylothorax is defined as the presence of lymph in the pleural space. Congenital chylothorax is one of the most frequent causes of fetal pleural effusion. It may be primary or secondary. Careful assessment of the etiology and of possible associated anomalies is required. Main complications are pulmonary hypoplasia, hydrops fetalis and the risk of premature delivery. Management is still a mater of controversy, the diagnosis of fetal pulmonary hypoplasia being difficult in utero. Factors such as gestational age, evolution of pleural effusion on two weeks, signs of seriousness (hydrops fetalis), and pulmonary expansion after pleural puncture may help the physician to choose between abstention, pleural tapping or long-term in utero drainage. Post natal treatment consists of pleural drainage and assisted ventilation in cases of respiratory distress, correction of metabolic and immune disorders and exclusive parenteral nutrition. Once chylothorax is resolved, formula feeding without long-chain triglycerides is allowed. If pleural effusion persists despite a well conducted treatment, albumin infusion and diuretics may be used before considering surgical treatment.