Cytogenetics of fetal anomalies detected by ultrasonography

Ultrasound is one of the most important technological advances introduced into modern obstetrics; its use has revolutionized the prenatal detection of foetal structural anomalies The aim of this study was to estimate the risk of chromosomal abnormalities associated with different foetal anomalies detected prenatally at the time of routine ultrasound screening. A prospective study was done on 344 fetuses with one or more structural foetal anomalies detected during routine antenatal second or third trimester scanning by ultrasonography between January 2003 and December 2006. Maternal age ranged between 17 and 43 years [mean 29 +/- 6 years] and gestational age ranged between 18 and 25 weeks [mean 20 +/- 1 weeks]. Foetal anomalies detected in this study included neural tube defects [NTD], renal anomalies, congenital heart disease [CHD], skeletal anomalies, cystic hygroma, anterior abdominal wall defects and intrauterine growth retardation [IUGR]. Cytogenetic analysis was done to all 344 samples and revealed normal 46, XX female or 46, XY male karyotyping in 272 samples [79.07%], and abnormal karyotype in 72 cases [20.93%]. Chromosomal abnormalities included trisomies in 34 cases [9.88%], monosomies mainly Turner syndrome in 28 cases [8.13%], polyploidies and structural chromosomal rearrangements including chromosome 22 microdeletion in 10 cases [2.9%]. In conclusion: foetal structural anomalies are usually associated with high risk of chromosomal abnormalities and foetal karyotyping is mandatory to verify the underlying aetiology and offer proper genetic counseling.

Acrocallosal syndrome [ACS]

Acrocallosal syndrome [ACS] is a rare autosomal recessive genetic disorder with hypoplasia / agenesis of corpus callosum, moderate to severe mental retardation, characteristic craniofacial abnormalities, distinctive digital malformations and growth retardation. In this paper we present a three month old girl with typical features of this syndrome.

Extended metabolic screen in sick neonates and children

Inborn errors of metabolism [IEM] are rare hereditary diseases resulting from incompetence in enzymatic reactions of intermediary metabolism. They are responsible for a significant level of neonatal and pediatric morbidity and mortality. There are 2 main problems in detecting IEM, first: symptoms are non-specific and often similar to those of sick neonates, therefore, only a small number of these diseases will be diagnosed from typical clinical picture alone and we can rarely target the specific investigation required for diagnosis of the offending disease. Secondly, investigations are complex and expensive. In Egypt, with limited facilities, extended metabolic screening [EMS] for sick neonates and children with symptoms indicative of IEM would be the best choice. This approach is called selective screening. In this paper, Extended Metabolic Screen was done to 231 cases [44 neonates and 187 children] with different symptoms suggesting IEM. Abnormal results were found in 22.73% of neonates and in 26.66% of those with previous neonatal death. First cousin marriage was present in 80% of neonates with abnormal EMS. Abnormal screen included organic acidemias [13.63%], amino acid Opathies [4.55%], and fatty acid oxidation defects [4.55%]. On the other hand, 8.56% of children had abnormal results. This included amino acid opathies [5.88%], organic acidemias [1.07%], cystic fibrosis [CF], congenital adrenal hyperplasia [CAH], and congenital hypothyroidism [CH] [1.61%]. We also found that 6.48% of children presenting with mental retardation had phenyl ketonuria [PKU], and nearly 10% of Children presenting with convulsion had MSUD, and another 10% had CAH. To conclude, selective screening to sick neonates and children with a simple, relatively cheap method like Extended Metabolic Screen [EMS] is the best cost effective test with high detection rate for IEM in neonates and children especially in Egypt with both high rate of consanguinity and limited facilities. A national screening program for PKU is extremely essential and increased awareness of the clinical presentation of the disease is a priority

Down syndrome in Egypt

Down syndrome [DS] is the most common and best-known chromosomal disorder and is the single most common genetic cause of mental retardation. Governmental care of this syndrome and other handicapping conditions has increased tremendoussly in the past few years to the extent that DS phenotype has become a phobia and many parents and/or physicians referred normal babies for karyotype for suspicion of chromosomal anomalies or for reassurance of their parents. On the other hand, prenatal screening is still inaccessible to most families and almost all cases of Down syndrome are diagnosed postnatally. In this paper we present the first and the largest study on DS patients from different regions all over Egypt aiming to look for possible causal factors for this high prevalence, and to evaluate the trend of parents and clinicians to the new screening programs and prenatal diagnosis. The Study included 1100 patients referred as DS, 1030 cases were confirmed by Cytogenetic analysis to be DS. Most of these cases [98.43%] were diagnosed postnatally and only 1.56% were detected prenatally mainly through mniocentesis and rarely products of conception [0.01%]. Their ages ranged from one hour to 30 years with median of 3 months. Males represented 54.13% while females represented 45.87% of the studied group. Mean maternal age at conception was 31.8 years for cases with non disjunction and 24.5 years for cases with translocation. All mothers of cases of translocation DS were under 35 years, in contrast to mothers of non disjunction cases in which 41.48% were above 35. Paternal age ranged from 19 to 62 years with mean of 36.5 years in non-disjunction cases and from 24-35 years in translocation cases with mean of 30.6 years. Consanguineous marriage was present in 12% of cases. Positive family history was present in 6% of cases. Most of cases were the first or the second in order of birth, and the most common cause of referral was dysmorphic features in live births and advanced maternal age in prenatally referred cases. Karyotype revealed that 93.98% of cases had non-disjunction, 3.5% of cases had translocation and 1.84% had mosaicism. Non classical karyotype was present in 7 cases [0.68%]. Most of the cases of translocation were t [21; 21], which was present in 51.35% of cases, followed by t [14; 21], which was present in 40.5% of cases, t [13; 21] in 5.4%, and t [15; 21] in 2.7% of cases of translocation. In conclusion, in Egypt with 1.6 million births / year and estimated risk of 2285 DS births annually, the concept of preventive genetics should be reinforced with a national policy targeting both health professionals and general public to offer prenatal genetic screening for all pregnant ladies and prenatal diagnosis for screen positive cases. This needs an integrated system including proper integrated diagnostic facilities, trained personnel and professional staff