Three cases of dup(10p)/del(10q) syndrome resulting from maternal pericentric inversion

Two families and 3 patients with dup(10p)/del(10q) syndrome segregating from a maternal pericentric inversion are described, including a stillborn female with Potter sequence and multicystic renal dysplasia. Comparison of 32 dup(10p) patients to 11 del(10)(q25) patients emphasized dolichocephaly, wide sutures, frontal bossing, micrognathia, and renal defects as distinguishing characteristics of the dup(10p) syndrome. The 3 new and 6 previously reported dup(10p)/del(10q) patients had several manifestations in common with the dup(10p) and del(10q) syndromes, but were more typical of dup(10p) syndromes, with respect to all 5 distinguishing characters. © 1993 Wiley-Liss, Inc.     

Monosomy 10qter due to a balanced familial translocation: t(10;16)(q25.2;q24)

A third case of monosomy 10q is described. The infant was severely malformed and died at day 9 post partum. The clinical symptoms are compatible with the two previous cases.     

Familial balanced insertion (5;10) and monosomy and trisomy (10) (q24.2→q25.3)

The phenotype of a boy with monosomy of a small segment of chromosome (10) (q24.2----q25.3) is described. In his family a balanced insertion (5;10) is found in three generations. Moreover there are two persons who are trisomic for the same small segment of chromosome 10 for which the boy is monosomic.     

Partial trisomy 3q syndrome inherited from familial t(3;9)(q26.1; p23)

A five-year-old girl was referred to prometaphase chromosome analysis because of mental retardation, facial dysmorphic features suggestive of Cornelia de Lange syndrome, cleft palate and additional minor congenital malformations of the cardiac system and fingers and toes. A familial balanced translocation (3;9)(q26.1; p23) was found. The karyotype of the proposita was 46,XX,der(9),t(3;9)(q26.1;p23). Thus the patient was trisomic for 3q26.1-qter and monosomic for 9p23-pter. The unbalanced chromosome constitution was not detected by standard Q-banding analysis shortly after birth. The karyotype was misdiagnosed as 46,XX,9(p+) in the proposita and her mother, and thought to be a normal variant of chromosome 9. The repeated cytogenetic study led to the diagnosis of the translocation and to the possibility of prenatal diagnosis in the translocation carriers. A survey of 22 published cases of dup(3q) showed that nearly 60% were secondary to familial balanced rearrangements with an excess of maternally derived abnormal chromosomes 3. Red blood cell galactose-1-phosphate-uridyltransferase (GALT) activity was normal in the patient, consistent with previous assignment of the gene locus for GALT to 9p13 (Shih et al. 1982).     

Identification and molecular confirmation of a small chromosome 10q duplication [dir dup(10)(q24.2→q24.3)] inherited from a mother mosaic for the abnormality

We describe a family in which two siblings exhibited developmental delay, reduced muscle tone and mild muscle weakness. Cytogenetic evaluation demonstrated that both children had a tandem duplication of a small portion of the long arm of chromosome 10 [46,XX or XY,dir dup(10)(q24.2→q24.3)], inherited from their clinically normal mother, who was found to be mosaic for the duplicated chromosome 10. Fluorescence in situ hybridization approaches, including total chromosome painting and the use of regional specific cosmid probes, were used to confirm the chromosome 10q origin of the duplicated material. This is the smallest confirmed duplication of this portion of chromosome 10 reported to date. © 1995 Wiley-Liss, Inc.     

Duplication 8q syndrome due to familial chromosome ins(10;8)(q21;q212q22)

We describe a kindred in which an ins(10;8)(q21;q212q22) chromosome rearrangement has been segregating for at least four generations. The risk for balanced carriers to have offspring with duplication of 8q212→8q22 is about 0.31. Individuals with unbalanced chromosomes are mildly to moderately mentally retarded and have a similar unusual appearance. Other manifestations include highly arched or cleft palate (8/9), micrognathia (6/9), sloped shoulders (4–6/9), convulsions (4/9), camptodactyly (3/9), pectus excavatum (2/9), elbow contractures (1/9), and postaxial polydactyly (1/9). The appearance and habitus resemble the mosaic trisomy 8 syndrome, although other anomalies of mosaic trisomy 8, such as vertebral, patellar, and renal defects, were not demonstrated.     

Origin of a paternal (13q; 15q) translocation leading to dup(13q) in two half sibs

We report on two half-sibs, a male and a female with dup(13)(q1405 → qter) that resulted from a der(15),t(13;15)(15qter → 15q25::13q1405 → 13qter), h +, pat. Their manifestations were similar to those with duplication of the distal half 13q. The father was a balanced de novo translocation carrier. Since the der(15) had a long secondary constriction, it was possible to trace the site of the mutation to the germ cell of the patients paternal grandmother who had this distinctive long secondary constriction in one of her normal 15 chromosomes.     

Familial t(11;13)(q21;q14) and the duplication 11q, 13q phenotype

Cases of duplication of distal 11q or proximal 13q have been reported independently. A specific translocation resulting in duplication of distal 11q, [der(22)t(11;22)(q23;q11)], has been documented in over 40 cases. We report on a male fetus with chromosomal excess of both distal 11q and proximal 13q resulting from a familial translocation. This case supports the causal association of duplication 11q with neural tube defects. © 1993 Wiley-Liss, Inc.     

Partial 18q trisomy and 18p monosomy resulting from a maternal pericentric inversion,inv(18)(p11.2q21.3)

A 7-year-old boy with dysmorphic features was found to have a recombinant chromosome 18, rec(18), resulting from meiotic recombination of a maternal pericentric inversion, inv(18) (p11.2q21.3), as defined by high-resolution banding. He was trisomic for the long arm (q21.3-qter) and monosomic for the short arm (p11.2-pter) of chromosome 18. His clinical features were compared with those in other rec(18) cases, and also those in monosomy 18p, trisomy 18qter and full trisomy 18 syndromes. The risk of recombinant formation for inv(18) carriers was also discussed.     

t(15;21)(q15;q22.1)pat resulting in partial trisomy and partial monosomy of chromosomes 15 and 21 in two offspring

Two sibs, carriers of unbalanced products of the translocation t(15;21)(q15;q22.1)pat, are described. The sister had Prader-Willi syndrome due to deletion 15 (pter > q15) and partial trisomy 21 (pter > q22.1); her brother had partial trisomy 15 (pter > q15) and partial monosomy 21 (pter > q22.1). The translocation breakpoint on chromosome 21 was located proximal to the SOD1 gene, within a region of 4.0 cM (2.3 Mb) between the loci D21S217 and D21S213. The correlations between the clinical presentation and the molecular findings of the two sibs are discussed in relation to other patients with partial trisomy and monosomy 21. © 1996 Wiley-Liss, Inc.     

Partial trisomy 3q due to a de novo translocation t(X;3) (p21;q12)

A patient with several congenital malformations, principally in the face, cardiovascular system and genitalia, was found to have the karyotype 46 ,X,der(X),t,X;3)(Xqter← p21::3ql2-←3qter). A comparison of the clinical and cytogenetical findings with similar cases in the literature led to the conclusion that a partial trisomy 3q is the most likely cause for the symptoms in this patient.     

Craniosynostosis in an infant with an interstitial deletion of 15q [46, XY,del(15)(q15q22.1)]

An interstitial deletion of 15q [46, XY, del(15)(q15q22.1)] was found in a malformed infant with craniosynostosis. Although the parents had normal chromosomes, the study of heteromorphic markers of chromosome 15 showed that the deleted chromosome 15 was of paternal origin. The 2 previously reported cases with an interstitial deletion of the middle portion of 15q were not complicated with craniosynostosis, and their deleted region did not include 15q15 band. The deletion of chromosome band 15q15 might be responsible for craniosynostosis.     

Neonatal death in cousins with trisomy 10q and monosomy 4p due to a familial translocation

Two cousins with trisomy for a part of the long arm of chromosome 10 and monosomy for the distal portion of the short arm of chromosome 4 are reported. These infants had severe, neonatally lethal, multiple malformations. Certain of these malformations - including severe lower limb reductions, marked ophthalmologic anomalies and certain craniofacial features - are inconsistent with either a simple additive effect of the two component chromosomal anomalies, or chromosomal "epistasis" that would result in observing the phenotypic effect of only one of the chromosomal aberrations. Rather a synergistic effect of these two karyotypic anomalies has resulted in unique phenotypic features.     

Interstitial deletion of chromosome 5 in a neonate due to maternal insertion,ins(8;5)(p23;q33q35)

We describe an infant girl with an interstitial deletion of chromosome bands 5q33 to 5q35 inherited from a maternal interchromosomal insertion ins(8;5)(p23;q33q35) which was demonstrated by fluorescent in situ hybridization with whole chromosome paints. Physical anomalies included hypertonicity, microcephaly, short neck, apparently low-set ears, micrognathia, camptodactyly, mild rocker bottom feet, and hammer toe. Cardiac anomalies included a large ventricular septal defect, patent ductus arteriosus, pulmonary hypertension and hypoplastic right ventricle. She died at age 3 months. Am. J. Med. Genet. 86:289–293, 1999. © 1999 Wiley-Liss, Inc.     

Partial trisomy 16q in two boys resulting from a maternal translocation, t(15;16) (p12;q11)

Two male infants with almost complete trisomy 16q due to a maternal translocation, are reported. The phenotypic similarities of these patients who had trisomy 16q11 leads 16qter and of the eight previously published reports of partial trisomy 16q, were compared.     

Del(10)(q22.3q24.1) associated with juvenile polyposis

Juvenile polyps are the most frequent gastrointestinal polyps with a malignant potential for which the genetic basis is unknown. Juvenile polyps, with a normal epithelium but hypertrophic lamina propria, are histologically quite distinct from adenomatous polyps which have dysplastic changes in epithelial nuclei. Furthermore, the adenomatous polyposis coli (APC) gene on Chr 5, mutated somatically in adenomatous polyps and mutated in the germline of patients with familial adenomatous polyposis, is not linked to hereditary juvenile polyposis. We provide the first report indicating that a tumor suppressor gene associated with juvenile polyposis may be located at 10q22.3q24.1. Cytogenetic studies of a patient with juvenile polyposis and multiple congenital abnormalities of the head, extremities, and abdomen revealed a de novo interstitial deletion of Chr 10 as the only defect, del(10)(10q22.3q24.1). Am. J. Med. Genet. 70:361–364, 1997. © 1997 Wiley-Liss, Inc.     

Maternal balanced translocation leading to partial duplication of 4q and partial deletion of 1p in a son: Cytogenetic and FISH studies using band-specific painting probes generated by chromosome microdissection

A 9-month-old boy with pre- and post-natal growth retardation, microcephaly, plagiocephaly, and several minor anomalies had the initial karyotype: 46,XY,der(1)t(1;?)(p36.1;?). Further analysis showed that the der(1) was derived from an unfavorable segregation of a maternal complex chromosome rearrangement, i.e., 46,XX,der(1)t(1;?)(p36.1;?), der(4)t(4;?)(q?;?). Whole chromosome fluorescence in situ hybridization (FISH) and chromosome microdissection were used to clarify the maternal karyotype as: 46,XX,der(1)t(1;4)(4qter→4q33::1p36.13→1qter),der(4)t(1;4)inv(4)(4pter→ 4q31.3::1p36.33→1p36.13::4q33→4q31.3::1p36.33→1pter). Therefore, the karyotype of the boy actually was 46,XY,der(1)t(1;4)(p36.13;q33). Clinical comparison of the patient's clinical findings showed similarities to individuals with partial del(1p) and dup(4q). To our knowledge the above cytogenetic abnormalities have not been described previously. This case further demonstrates the advantages of chromosome microdissection and FISH in the identification of anomalous chromosome regions and breakpoints. Am. J. Med. Genet. 71:160–166, 1997. © 1997 Wiley-Liss, Inc.     

Syndrome of facial,oral, and digital anomalies due to 7q21.2→q22.1 duplication

We report on an 18-year-old man with moderate mental retardation, multiple congenital anomalies and partial trisomy 7q21.2→q22.1, as the unbalanced product of a familial balanced 7q/6q insertion translocation. To the best of our knowledge, this is the first example of interstitial trisomy 7q21.2→q22.1 reported. The syndrome is characterized by the presence of facial, oral, and digital anomalies: 1) macrocephaly with frontal bossing, hypertelorism, small palpebral fissures with downward slant; 2) lobulated tongue, multiple intrabuccal frenula, oligodontia and enamel hypoplasia; 3) cutaneous syndactyly of fingers II-III and III-IV, broad and short fingertips with fetal pads, broad thumbs, and halluces. Am. J. Med. Genet. 80:454–458, 1998. © 1998 Wiley-Liss, Inc.