Prenatal diagnosis of a 22q11 deletion in a second-trimester fetus with conotruncal anomaly, absent thymus and meningomyelocele: Kousseff syndrome

A 30-year-old nulliparous woman was seen for a detailed ultrasound scan at 20 weeks of gestation. The scan revealed a male fetus with truncus arteriosus, membranous ventricular septal defect, absent thymus and sacral meningomyelocele. A 46,XY karyotype with a 22q11 deletion was detected. The parents chose to terminate the pregnancy. The pathological autopsy showed normal facial structures, minimal ventricular dilatation in the brain and a sacral meningomyelocele. Overlapping toes and a left claw-hand were also noted. An aplastic thymus with absent parathyroid glands was detected. The cardiac examination was consistent with the ultrasound diagnosis. The parental karyotypes were both normal. Kousseff syndrome is caused by a chromosome 22q11 deletion. It includes sacral meningomyelocele and conotruncal heart defects, unlike DiGeorge syndrome. Obstetricians should consider this a not so rare entity when they detect conotruncal abnormalities and a meningomyelocele as part of a 22q11.2 deletion syndrome.     

Female pseudohermaphroditism in a fetus with a deletion 9(q22.2q31.1)

Interstitial deletions of chromosomal region 9q are rarely seen. We report the first prenatal diagnosis of a de novo interstitial deletion 9q. The fetus was karyotyped for intrauterine growth retardation (IUGR). Conventional and molecular cytogenetics showed female karyotype with a de novo deletion of the chromosomal region 9(q22.2q31.1) leading to a partial monosomy 9q. At autopsy, the fetus showed growth retardation, dysmorphy, and a female pseudohermaphroditism. These results suggest that a gene(s) for genital development reside in chromosomal region 9q22.2q31.1.     

Oesophageal atresia with a terminal deletion of chromosome 2q37.1

We herein report the case of a newborn girl with oesophageal atresia associated with cardiac and gastrointestinal anomalies, including patent ductus arteriosus, tracheomalacia, and gastro-oesophageal reflux with hiatus hernia. In addition, she had a terminal deletion of the long arm of chromosome 2, with a breakpoint of 2q37.1. The patient died following a cardiac arrest at 90 days of age. No cause of death was identified at autopsy.     

Molecular cytogenetic characterization of Jacobsen syndrome (11q23.3-q25 deletion) in a fetus associated with double outlet right ventricle,hypoplastic left heart syndrome and ductus venosus agenesis on prenatal ultrasound

Objective

We present molecular cytogenetic characterization of Jacobsen syndrome (11q23.3-q25 deletion) in a fetus associated with double outlet right ventricle (DORV), hypoplastic left heart syndrome (HLHS), and ductus venosus (DV) agenesis on prenatal ultrasound.

Complex cardiac defect with hypoplastic right ventricle in a fetus with valproate exposure

We describe a fetus with a hypoplastic right ventricle detected by prenatal ultrasound examination. A possible causal relationship with prenatal valproate exposure is discussed.     

Prenatal diagnosis of familial 22q11.2 deletion syndrome in a pregnancy with concomitant cardiac and urinary tract abnormalities in the fetus and the mother

ObjectiveWe present prenatal diagnosis of familial 22q11.2 deletion syndrome in a pregnancy with concomitant cardiac and urinary tract abnormalities in the fetus and the mother.Case reportA 28-year-old woman primigravid underwent amniocentesis at 23 weeks of gestation because of fetal ultrasound findings of aortic stenosis, interrupted aortic arch (IAA), left multicystic kidney, right hydronephrosis and ureterocele. Amniocentesis revealed a karyotype of 46,XX. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr 22q11.21 (18,894,835-21,505,417) × 1.0 [GRCh37 (hg19)] with a 2.611-Mb 22q11.21 deletion encompassing 41 Online Mendelian Inheritance in Man (OMIM) genes including UFD1L, TBX1, GNB1L, COMT and MED15. aCGH analysis on the DNAs extracted from parental bloods confirmed that the mother carried the same 22q11.21 microdeletion. Level II ultrasound additionally found ventricular septal defect (VSD) and persistent left superior vena cava (PLSVC). Examination of the woman showed short stature, malar hypoplasia, hypertelorism, bulbous nasal tip, prominent nasal root, hypoplasia of nasal wings, right renal agenesis, left ureterovesical reflux and VSD with repair, but normal intelligence and normal neuropsychiatric development. The woman decided to continue the pregnancy, and a 2903-g female baby was delivered at 38 weeks of gestation with left multicystic kidney, right hydronephrosis, dysgenesis of corpus callosum, IAA, VSD, PLSVC, patent ductus arteriosus, patent foramen ovale, atrial septal defect, dilated main pulmonary artery and tricuspid regurgitation. The neonate died at the age of one month.ConclusionPrenatal diagnosis of concomitant congenital heart defects and urinary tract abnormalities in the fetus and the parent should raise a suspicion of familial 22q11.2 deletion syndrome.     

Pulmonary atresia with hypoplastic right ventricle. A clinical embryological study

An unusual case of pulmonary atresia with an aberrant karyotype of 46,XX,t(6;8)(p21.2;q11.2) is reported. Fetal ultrasonic examination at the 20th week of gestation revealed a hypoplastic right ventricle and an intact interventricular septum. Authors summarize their postnatal findings in fetal heart and the large adjacent vessels with special reference to the pathogenesis of this rare congenital heart defect. The observation delineates right-ventricular outflow tract obstruction associated with an abnormal pulmonary blood supply. The anatomy of the systemic pulmonary collaterals was studied and correlated with multifocal disorders in the system of the pharyngeal arch arteries in the early embryonic development.     

Labyrinthine malformation in the 22q11.2 deletion syndrome

Velocardiofacial syndrome and DiGeorge syndrome, integrating to form the 22q11.2 deletion syndrome, manifest frequently with hearing loss. Instead, a labyrinthine anomaly is only occasionally described in velocardiofacial syndrome/DiGeorge syndrome. We report a vestibular labyrinthine malformation demonstrated with computed tomographic scan in a patient with a palatal cleft and a 22q11.2 deletion presenting as velocardiofacial syndrome.     

Prenatal diagnosis of a fetus with terminal deletion of chromosome 1 (q41)

Many authors have suggested that individuals affected by a terminal 1q deletion display a phenotypically definable and recognizable syndrome. In all of the 27 cases reported to date, the breakpoints were at band q42 or distally to it. To our knowledge, we report the first case of a terminal 1q41 deletion. Diagnosis was made prenatally by amniocentesis, following ultrasonographic diagnosis of omphalocele, cerebral ventriculomegaly, and increased nuchal fold thickness in a 19-week female fetus. Multiple facial and extremity features were consistent with the proposed distal 1q deletion syndrome; omphalocele, however, has not been reported previously. The absence of liver herniation into the omphalocele sac in this case supports the previously reported association of this finding with chromosomal anomalies.     

Molecular cytogenetic characterization of 1q42.3q44 deletion and 8q24.3 duplication in a fetus with single umbilical artery and ventricular septal defects

ObjectiveWe present prenatal diagnosis and molecular cytogenetic characterization of a chromosome 1q42.3q44 deletion and 8q24.3 duplication in a fetus with single umbilical artery and ventricular septal defects, and we discuss the genotype–phenotype correlation.Case reportHere, we describe a fetus with abnormal sonography findings showing a single umbilical artery and ventricular septal defects. Conventional karyotyping initially described the fetus as 46,XX,1q? and molecular cytogenetic analysis (CMA) revealed a 13-Mb deletion and 4.6-Mb duplication of regions 1q42.3q44 and 8q24.3, respectively. The father's karyotype was 46,XY. The mother's karyotype was 46,XX,t(1;8)(q42;q24). Therefore, the karyotype of the fetus was identified as 46,XX,der(1)t(1;8)(q42;q24) mat. After genetic counseling, the couple chose to terminate the pregnancy. We suggest that the ACTN2, RYR2 and PUF60 genes may be responsible for the ultrasound abnormalities observed in the fetus.ConclusionTo the best of our knowledge, this is the first report of a 1q deletion and 8q duplication identified by prenatal detection. The application of karyotype analysis and CMA provides more accurate characterization for unidentified chromosomal anomalies, and benefits appropriate genetic counseling in the clinic.     

22q13 deletion syndrome with central diabetes insipidus: a previously unreported association

We describe a two-year-old girl with 22q13 deletion syndrome (MIM # 606232), 46, XX, de l (22) (q13.31). ish del (22) (q13.31) (TUPLE 1+,ARSA-). The patient has hypotonia, normal growth, severe expressive language delay, mild mental retardation, and minor dysmorphic facial features. In addition, she had central diabetes insipidus that was diagnosed at age two days and resolved at age 27 months. To our knowledge, this association has not been reported previously. Infants with hypotonia, or those suspected to have this syndrome should have high-resolution chromosome analysis and fluorescent in situ hybridization (FISH) studies or molecular analysis, since the chromosomal deletion may be subtle and may go undetected on routine cytogenetic studies. The association of 22q13 deletion syndrome with central diabetes insipidus is reported for the first time.     

Prenatal diagnosis of absent right and persistent left superior vena cava

OBJECTIVE: Persistence of left superior vena cava (LSVC) is a known variant of the systemic venous return. In the setting of an otherwise structurally normal heart, absence of the right superior vena cava (RSVC) but persistence of the LSVC is rare. METHODS: We describe the prenatal findings of a fetus with absent right and persistent LSVC. RESULTS: A dichorionic diamniotic twin pregnancy was referred to our centre with cardiac disproportion. Twin A had disproportion at four-chamber level, an absent right but persistent LSVC draining to an enlarged coronary sinus and a hypoplastic transverse aortic arch (<2 mm). Postnatal echocardiography of the asymptomatic baby confirmed the prenatal diagnosis, and serial echocardiograms demonstrated general hypoplasia of the aortic arch but no discrete coarctation (CoA). No intervention was required and the baby is thriving aged 10 months. CONCLUSION: Persistence of LSVC is a known variant of the systemic venous return. In the setting of an otherwise structurally normal heart, absence of the right but persistence of LSVC is rare.     

Recombination of a maternal pericentric inversion results in 22q13 deletion syndrome

We describe a 10-month-old boy with 22q13 deletion syndrome. Chromosomal analysis showed a partial duplication of 22p11.2-pter and a terminal deletion of 22q13.31-qter. Maternal chromosomal analysis showed a pericentric inversion of chromosome 22, with breakpoints at p11.2 and q13.31 [inv(22)(p11.2q13.31)]. The deleted chromosome resulted from a recombinant chromosome inherited from his mother. This is a rare case of 22q13 deletion syndrome associated with parental pericentric inversion of chromosome 22.     

Persistent fifth aortic arch associated with 22q11.2 deletion syndrome.

BACKGROUND: Chromosome 22q11.2 deletion is frequently associated with conotruncal malformations and aortic arch anomalies. This study investigated the association of chromosome 22q11.2 deletion with clinical manifestations in four pediatric patients with persistent fifth aortic arch. METHODS: Four patients with persistent fifth aortic arch treated between July 1997 and June 2004 were included in this retrospective study. There were two girls and two boys, aged 2 days to 11.3 years, with persistent fifth aortic arch and cardiac conotruncal malformations. Chart recordings, plain chest films, two-dimensional and Doppler echocardiograms, cardiac catheterization with angiograms, surgical findings, and cytogenetic study were analyzed. RESULTS: Clinically, all four patients had the cardinal phenotypic features of 22q11.2 deletion syndrome, including cardiovascular malformations (conotruncal malformations and aortic arch anomalies), abnormal facies, thymic hypoplasia, canopy anomaly of the palate (high-arched palate, rather than cleft palate), and hypocalcemia (or hypoparathyroidism). All four patients were confirmed to have chromosome 22q11.2 deletion. CONCLUSION: Congenital conotruncal malformations, including tetralogy of Fallot with pulmonary atresia or stenosis, and aortic arch anomalies including a persistent fifth aortic arch or a right aortic arch, should lead to suspicion of chromosome 22q11.2 deletion when manifested together with any one of the other four cardinal phenotypic features.