Trisomy 11 q (q23.1 - qter) through maternal translocation t(11;22) (q23.1;q11.1). A new case]

A 4-year-old boy with partial trisomy 11q resulting from malsegregation of a maternal translocation, t(11;22)(q23.1;q11.1), exhibits the following malformations: severe mental deficiency; growth retardation and hypotonia; brachycephaly with flattened occiput and forehead; facial dysmorphia; pre-auricular fistula. These features are in good agreement with the syndrome recently described for partial trisomy 11q. The translocation appears to be identical in that in three other families already reported.     

Emanuel syndrome due to unusual segregation of paternal origin

Emanuel syndrome is an inherited chromosomal abnormality resulting from 3:1 meiotic segregation from parental balanced translocation carrier t(11;22)(q23;q11), mostly of maternal origin. It is characterized by mental retardation, microcephaly, preauricular tag or sinus, ear anomalies, cleft or high arched palate, micrognathia, congenital heart diseases, kidney abnormalities, structural brain anomalies and genital anomalies in male. Here in, we describe a female patient with supernumerary der(22) syndrome (Emanuel syndrome) due to balanced translocation carrier father t(11;22) (q23;q11). She was mentally and physically disabled and had most of the craniofacial dysmorphism of this syndrome. Our patient had cleft palate, maldeveloped corpus callosum and hind brain with normal internal organs. Additionally, arachnodactyly, hyperextensibility of hand joints, abnormal deep palmar and finger creases, extra finger creases and bilateral talipus were evident and not previously described with this syndrome. Cytogenetic analysis and FISH documented that the patient had both translocation chromosomes plus an additional copy of der(22) with karyotyping: 47,XX,t(11; 22)(q23;q11),+der(22)t(11;22)(q23;q11). We postulated that this rare chromosomal complement can arise from; 2:2 segregation in the first meiotic division of the balanced translocation father followed by non-disjunction at meiosis II in the balanced spermatocyte.     

Partial trisomy (11;22) syndrome with manifestations of Goldenhar sequence due to maternal balanced t(11;22)

Here we report a 15-year-old girl patient who had severe mental and growth retardation, cleft palate, hemifacial microsomia, skin tags, hypoplasia of the external auditory canal, scoliosis and renal agenesis. Our patient was the fourth child of nonconsanguineous marriage. Peripheral blood chromosomal analysis of the patient revealed 47,XX,+der(22)t(11;22)(q23;q11). The maternal karyotype was reported as 46,XX,t(11;22)(q23;q11). Maternal balanced translocation t(11;22)(q23;q11) causing Goldenhar syndrome with 47,XX,+der(22) has not been reported previously. The presented case clearly indicates that in every case with Goldenhar syndrome, chromosome analysis should be done for the possibility of unbalanced translocations.     

Supernumerary chromosome der(22)t(11;22): Emanuel syndrome associates with novel features

Emanuel syndrome results from +der(22)t(11q23;22q11). Cleft palate, ear anomalies, heart defects, genital anomalies, hypotonia, and mental retardation are the main features of the syndrome. We report a nine-year-old boy with the t(11;22)(q23;q11) chromosome, transmitted in an unbalanced fashion from his mother, and originated in the maternal grandmother's meiosis. In addition to mental retardation, hypotonia, craniofacial anomalies, and cryptorchidism, he has novel findings such as, joint hyperextensibility, left liver lobe agenesis, left sided malposition of the gallbladder and pancreas hypoplasia. This is the first report associating these features with Emanuel syndrome.     

Der(22) syndrome and velo-cardio-facial syndrome/DiGeorge syndrome share a 1.5-Mb region of overlap on chromosome 22q11

Derivative 22 (der[22]) syndrome is a rare disorder associated with multiple congenital anomalies, including profound mental retardation, preauricular skin tags or pits, and conotruncal heart defects. It can occur in offspring of carriers of the constitutional t(11;22)(q23;q11) translocation, owing to a 3:1 meiotic malsegregation event resulting in partial trisomy of chromosomes 11 and 22. The trisomic region on chromosome 22 overlaps the region hemizygously deleted in another congenital anomaly disorder, velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS). Most patients with VCFS/DGS have a similar 3-Mb deletion, whereas some have a nested distal deletion endpoint resulting in a 1.5-Mb deletion, and a few rare patients have unique deletions. To define the interval on 22q11 containing the t(11;22) breakpoint, haplotype analysis and FISH mapping were performed for five patients with der(22) syndrome. Analysis of all the patients was consistent with 3:1 meiotic malsegregation in the t(11;22) carrier parent. FISH-mapping studies showed that the t(11;22) breakpoint occurred in the same interval as the 1.5-Mb distal deletion breakpoint for VCFS. The deletion breakpoint of one VCFS patient with an unbalanced t(18;22) translocation also occurred in the same region. Hamster-human somatic hybrid cell lines from a patient with der(22) syndrome and a patient with VCFS showed that the breakpoints occurred in an interval containing low-copy repeats, distal to RANBP1 and proximal to ZNF74. The presence of low-copy repetitive sequences may confer susceptibility to chromosome rearrangements. A 1.5-Mb region of overlap on 22q11 in both syndromes suggests the presence of dosage-dependent genes in this interval.     

Pre-auricular tags and associated anomalies: considerations for genetic counseling

Pre-auricular tags are relatively common isolated congenital anomalies with a prevalence of about 5 per 1000 live births. Several associations with congenital anomalies have been reported and the opportunity of systematic ultrasonography examinations in these patients were debated in the literature. We conducted a retrospective epidemiological study on 95 affected newborns, to evaluate whether infants with pre-auricular tags may be at risk for associated anomalies. Our results focus the attention on the increased risk of congenital urinary tract and heart malformations in newborns with isolated pre-auricular tags. Therefore, we recommend that a carefully genetic clinical examination to evaluated dysmorphic features evocative of a specific pattern or syndrome and an urinary and cardiac ultrasonography should be performed in infants with isolated pre-auricular tags.     

Two cases of partial trisomy 10q syndrome due to a familial 10;20 translocation

We describe an eleven day-old boy and his first degree double cousin who both have distal trisomy 10q syndrome. Their cytogenetic analysis using GTG-banding showed an unbalanced translocation 46, XY, -20, +der(20), t(10;20)(q22.3, p11) mat and 46, XX, -20, +der(20), t(10;20)(q22.3, p11) mat. The translocation was confirmed by FISH. We have found balanced translocation t(10;20)(q22.3; p11) with cytogenetic and FISH studies in the mothers and maternal grandfather of these children. Our cases had typical craniofacial and visceral anomalies of this syndrome. However case 1 had an agenesia of corpus callosum which was not previously described and case 2 had hypertrophied cardiomyopathy and cliteromegaly which were previously described as rare anomalies for this syndrome.     

A Palindrome-Mediated Recurrent Translocation with 3:1 Meiotic Nondisjunction: The t(8;22)(q24.13;q11.21)

Palindrome-mediated genomic instability has been associated with chromosomal translocations, including the recurrent t(11;22)(q23;q11). We report a syndrome characterized by extremity anomalies, mild dysmorphia, and intellectual impairment caused by 3:1 meiotic segregation of a previously unrecognized recurrent palindrome-mediated rearrangement, the t(8;22)(q24.13;q11.21). There are at least ten prior reports of this translocation, and nearly identical PATRR8 and PATRR22 breakpoints were validated in several of these published cases. PCR analysis of sperm DNA from healthy males indicates that the t(8;22) arises de novo during gametogenesis in some, but not all, individuals. Furthermore, demonstration that de novo PATRR8-to-PATRR11 translocations occur in sperm suggests that palindrome-mediated translocation is a universal mechanism producing chromosomal rearrangements.     

Distal duplication 14q: Report of three cases and further delineation of the syndrome

Summary Three cases of distal duplication 14q are presented. The first two cases are cousins in a kindred segregating a balanced translocation t(14;18)(q31;q23). The third case resulted from a maternal translocation t(14;18)(q24;p11). By review of these cases and those previously reported, a distal duplication 14q syndrome is further delineated. Common features include postnatal growth retardation, mental retardation, hypotonia, microcephaly, slanted palpebral fissures, ocular hypertelorism, sparse eyelashes and eyebrows, nasal dysmorphism, tented lip, micrognathia, posteriorly rotated ears, and minor skeletal anomalies.     

The fetal phenotype of partial trisomy of the long arm of chromosome 4 (4q22----4qter).

A slightly malformed female fetus with partial trisomy 4q due to a maternal balanced translocation t(1;4)(q44;q22) is reported. This fetus presented some of the typical facial features and internal malformations associated with pure partial trisomy 4q indicating that chromosomal diagnosis is needed to confirm the reality of the malformative syndrome.     

Unbalanced karyotype due to adjacent 1 segregation of t(11;22)(q23.3;q13.2).

The 11q;22q translocations, whatever the breakpoints may be, are of particular interest because of their propensity to 3:1 segregation of the chromosomes at meiosis I. Until now, no unbalanced karyotype resulting from 2:2 adjacent segregation was published among offspring of 11q;22q translocation carriers. The authors report the case of an unbalanced karyotype due to adjacent 1 segregation of a maternal translocation (11;22)(q23.3;q13.2). The proband's karyotype was 46,XX,-22,+der(22)(11;22)(q23.3;q13.2)mat. This finding demonstrates that adjacent 1 segregation is possible in t(11;22) with breakpoints at 11q23 and 22q13, and can lead to birth of viable infants.     

Trisomy 1q43 syndrome: a consistent phenotype with macrocephaly, characteristic face, developmental delay and cardiac anomalies

Trisomy 1q43 syndrome: a consistent phenotype with macrocephaly, characteristic face, developmental delay and cardiac anomalies: Patients with trisomy (1)(q42-qter) present with psychomotor retardation, macrocephaly, occasional presence of facial capillary naevi, cardio-vascular anomalies and small size for gestational age. We report on a girl with the same pattern of malformations, who has pure trisomy 1 q43: duplication of the region (1) (q43) and the translocation of the terminal region of the other chromosome 1 to the derivative 1, narrowing down the critical region for the characteristic traits of severe developmental delay, macrocephaly and congenital cardiac malformations.     

Partial trisomy of the distal part of 10q: a report of two Egyptian cases

Partial trisomy of the distal third of the long arm of chromosome 10 is a well defined but rare syndrome. Most cases result from an unbalanced translocation. Growth retardation, developmental delay and characteristic dysmorphic features are well described in the syndrome. This report includes 2 Egyptian cases with partial 10q trisomy involving different breakpoints. Cases were subjected to full clinical examination and detailed cytogenetic analysis using conventional and FISH studies. Results showed that the karyotype of case 1 was 46,XX,der(7)t(7;10)(p22;q23).ish(wcp7+;wcpl0+) and the karyotype of case 2 was 46,XX,der(7)t(7;10)(p22;q25).ish(wcp7+;wcp 10+). The chromosomal abnormalities in case 1 resulted from a paternal balanced translocation while case 2 resulted from a maternal balanced translocation involving chromosomes 10 and 7 in both cases. The probands' phenotypes were correlated to the breakpoints and compared to previously reported cases with partial trisomy 10q. Both cases had the well characterized phenotype of the distal trisomy of 10q in the form of mental retardation, microcephaly, characteristic dysmorphic facies and limb anomalies as trisomy in both cases involved the 10q25-->qter region. However, case 1 with 10q23-->qter duplication showed more severe clinical manifestations than case 2 with less extensive 10q25-->qter trisomy. These included severe failure to thrive, cardiac involvement and death from respiratory and heart failure. This study confirmed that unbalanced chromosome regions of the long arm of chromosome 10 play an important role in developmental malformations and that a more severe form is associated with involvement of 10q23. It also emphasizes the importance of increasing public awareness regarding these chromosomal rearrangements and the importance of genetic counseling and prenatal diagnosis to avoid recurrences and associated family stress. This was clearly demonstrated in the second family in this study as the couple refused any follow up or further investigations due to religious beliefs despite their social and educational level.     

A family with segregation of an unbalanced translocation (7;13) (q36;q32) in three patients with severe mental retardation, microcephaly and dysmorphic features, detected by subtelomere FISH: genetic counselling and prenatal diagnosis

We report a Sardinian family in which three members showed a mental-retardation-microcephaly-multiple malformations syndrome resulting from an unbalanced translocation (7;13)(q36;q32) which led to subtelomeric trisomy 7q36qter and partial monosomy 13q32qter. The unbalanced translocation was transmitted by alternate segregation from a female and a male carriers of the balanced translocation. The three patients had severe mental retardation, microcephaly and multiple minor facial and fingers anomalies. Neuroimages showed brain atrophy, associated in two patients with partial agenesis of the corpus callosum. FISH with chromosome 13 and 7 specific painting probes and subtelomere specific probes was instrumental for defining and characterizing the chromosomal translocation. Extensive genetic counseling and prenatal diagnosis has been offered to all the members of the family.     

Rearrangements of chromosome 9 in different hematological neoplasias

In the present article the frequency of anomalies in chromosome 9 among children with hematological neoplasias amounted to 25/112 in acute lymphoblastic leukemia (ALL), 10/83 in acute myeloid leukemia (AML), and 3/20 in myelodysplastic syndrome (MDS). In ALL, deletions are encountered more often than translocations. Deletions are found in both single anomalies and as an element in complex karyotypes. The rearrangements involve the bands 9q34 and 9q22 the most often. The translocation t(9;22)(q34; q11) is encountered in 7.1% of all cases of ALL. In AML, translocation are found more often than deletions. Structural rearrangements most often involved the long arm, at bands 9q22 and 9q34. Deletions, duplications, and translocations were recorded in MDS. No relationship with the initial hematological indicators, including blastosis, were found. The studies attest to different directions of the clinical prognosis in the course of acute leukemia (AL) where there are deletions. Multidrug resistance and the continuing progress of the disease in the course of chemotherapy is found in t(9;22)(q34; q11).     

A 45,XX,-5,-14,+t(5q;14q)mat cri du chat child.

A two-year-old girl has the following features of the cri du chat syndrome: microcephaly, hypertelorism, downward slanting of the palpebral fissures, psychomotor retardation and a cat-like cry. She is only of five patients having the cat cry syndrome with 45 chromosomes. Her karyotype is 45,XX, -5, -14, +t(5; 14)(5qter leads to 5p11: : 14q11 leads to 14qter) with the translocation inherited from her mother and maternal grandmother, each of whom is the carrier of a balanced translocation 46,XX,t(5;14)(p11q11). Normal plasma activity for hexosaminidase B suggests the locus for this enzyme is not located in the delected segment of 5 p.     

Precocious puberty associated with partial trisomy 18q and monosomy 11q

We report a 10-years-old female patient with a partial trisomy 18q and monosomy 11q due to a maternal translocation. The phenotype of our proband is partially common with Jacobsen syndrome and duplication 18q but she has also some atypical anomalies such as precocious puberty, a retinal albinism and hypermetropia. Based on cytogenetics and FISH analysis, the karyotype of the proband was 46,XX,der(11)t(11;18)(q24;q13). To the best of our knowledge, this is the first report of precocious puberty associated with either dup(18q) or del(11q) syndromes.     

Partial trisomy of 11 and 22 due to familial translocation t(11;22) (q23;q11), inherited in three generations

Summary A 1-year-old girl with partial trisomy of 11 (q23qter) and 22 (pterq11) is presented. She had severe mental retardation, cleft palate, congenital heart disease, congenital dislocation of the hip, and other anomalies.The extra acrocentric chromosome was identified as der(22),t(11;22) (q23;q11) from a familial translocation and by G-and R-banding methods. The mother and the maternal grandfather were carriers of balanced rcp(11;22) (q23;q11) translocations.The possible relations between phenotypic features and the karyotypes of partial trisomy 11 and 22 are discussed.     

Familial translocation t(10;21)(q22;q22)

Summary A family is described with a translocation t(10;21)(q22;q22) transmitted through three generations. This family was studied for the apparition of several miscarriages and two sisters with multiple malformations. Both children had a probably partial trisomy of chromosome 10 and a monosomy of chromosome 21 due to a maternal adjacent-2 meiotic segregation.     

47,XY,+der(11;22)(q23;q12) following balanced translocation t(11;22)(q23;q12)mat

Summary Report of a supernumerary extra chromosome der(11;22)(q23; q12) resulting from a balanced translocation in the mother. The propositus suffers from mental deficiency, deafness and extreme muscular weakness and exhibits cleft palate, a labial lymphangioma and an atrial septum defect. Since the features of partial trisomy 11q23 frequently associated with a translocation t(11q;22q) bear similarities with the cases of so called trisomy 22 one might conjecture that some of these observations are in fact products of translocations including partial 11q.