Phenotypical characterization of 13q deletion syndrome: Report of two cases

Patients with 13q deletion syndrome are characterized with different phenotypical features depending on the size and location of the deleted region on chromosome 13. These patients fall into three groups: In Group 1, deleted region is in the proximal and does not extend into q32; in Group 2, deleted region involves proximal to the q32 and in Group 3 q33-q34 is deleted. We present two cases with 13q syndrome with two different deleted region and different severity on clinical features: One case with interstitial deletion belongs to the Group 1 with mild mental retardation and minor malformations and the other case with terminal deletion belongs to Group 3 with moderate to severe mental retardation and major malformations.     

Chromosome 7 short-arm interstitial deletion (p14)

Summary A 13-year-old girl presented with microcephaly, short and broad neck, low posterior hairline, congenital heart disease, limitation of joint movement, and mild mental retardation. Chromosomal analysis showed interstitial deletion of band p14 of the short arm of chromosome 7. The patient's physical and cytogenetic findings are compared with those of five other patients with 7p-deletions.     

The 8p-syndrome

A partial de novo deletion of 8p in a 10 1/2 month-old boy is described, the karyotype being 46,XY,del(8) (p21.3-qter:). Reduced birth weight, growth and psychomotor retardation, craniofacial dysmorphism with microcephaly and low set, deformed ears, stubby nose, wide set nipples, congenital heart defect and undescended testes were the main clinical findings. Death occurred at 2 1/2 years of age due to fulminant tracheo-bronchitis. Red cell glutathion reductase activity was normal. A review of previous cases with similar deletions outlines a definite clinical entity.     

Inherited ring chromosome 8 without loss of subtelomeric sequences

We report the first case of inherited ring chromosome 8 syndrome without loss of subtelomeric sequences. The proband is a 6 1/2-year-old boy with short stature, microcephaly, mild mental retardation, and behavioral problems including hyperactivity and attention deficit. His mother presented the same physical features but intelligence was normal. Family history also revealed an uncle and a grandmother, with short stature and microcephaly. Moderate mental retardation was reported in the uncle. Karyotypes and fluorescence in situ hybridization (FISH) analyses were performed on peripheral blood lymphocytes for both child and mother. The child's karyotype was reported as 46,XY,r(8)(p23q24.3)[24]/45,XY,-8[2] and the mother's karyotype 46,XX,r(8)(p23q24.3)[22]/45,XX,-8[2]/47,XX,r(8)(p23q24.3), +r(8)(p23q24.3)[1]. FISH studies showed no deletion of subtelomeric sequences for both child and mother indicating that no or little chromosomal euchromatic material has been deleted. These findings indicate that ring chromosome 8 without loss of subtelomeric sequences can be inherited and that carriers in a same family present with cognitive function ranging from mild mental retardation to normal intelligence.     

High-resolution mapping of genotype-phenotype relationships in cri du chat syndrome using array comparative genomic hybridization

We have used array comparative genomic hybridization to map DNA copy-number changes in 94 patients with cri du chat syndrome who had been carefully evaluated for the presence of the characteristic cry, speech delay, facial dysmorphology, and level of mental retardation (MR). Most subjects had simple deletions involving 5p (67 terminal and 12 interstitial). Genotype-phenotype correlations localized the region associated with the cry to 1.5 Mb in distal 5p15.31, between bacterial artificial chromosomes (BACs) containing markers D5S2054 and D5S676; speech delay to 3.2 Mb in 5p15.32-15.33, between BACs containing D5S417 and D5S635; and the region associated with facial dysmorphology to 2.4 Mb in 5p15.2-15.31, between BACs containing D5S208 and D5S2887. These results overlap and refine those reported in previous publications. MR depended approximately on the 5p deletion size and location, but there were many cases in which the retardation was disproportionately severe, given the 5p deletion. All 15 of these cases, approximately two-thirds of the severely retarded patients, were found to have copy-number aberrations in addition to the 5p deletion. Restriction of consideration to patients with only 5p deletions clarified the effect of such deletions and suggested the presence of three regions, MRI-III, with differing effect on retardation. Deletions including MRI, a 1.2-Mb region overlapping the previously defined cri du chat critical region but not including MRII and MRIII, produced a moderate level of retardation. Deletions restricted to MRII, located just proximal to MRI, produced a milder level of retardation, whereas deletions restricted to the still-more proximal MRIII produced no discernible phenotype. However, MR increased as deletions that included MRI extended progressively into MRII and MRIII, and MR became profound when all three regions were deleted.     

Familial interstitial deletion of chromosome 4 (p15.2p16.1)

Interstitial deletion of the proximal short arm of chromosome 4, extending from p14 to p16.1 region, results in a distinct clinical syndrome. This proximal 4p deletion syndrome is characterized by variable degrees of mental retardation, unusual facies and minor dysmorphic features. Majority of the patients also show a tall, ectomorphic habitus and normal to excessive linear growth with age. While there have been several cases of such interstitial del(4p) cases reported, familial transmission of this condition has not been documented in the literature. This is the first report of a familial transmission of proximal del(4p) from a mother to her daughter, with both patients showing similar features. This report of the familial transmission of del(4p) has wider implications in genetic counseling.     

Partial duplication 5q syndrome: phenotypic similarity in two sisters with identical karyotype (partial duplication 5q33 leads to 5qter and partial deficiency 8p23 leads to pter).

Two sisters with statomotor developmental retardation microcephaly, hydrocephalus internus and externus without signs of pressure, heart defect (ventricular septal defect), early pulmonary resistance and characteristic facial changes were found to have the same unbalanced karyotype with partial trisomy 5q3300 leads to 5qter and partial monosomy 8p2300 leads to 8pter, derived from a balanced reciprocal paternal translocation: 46,XY,t(5;8)(q3300;p2300). The older girl was tested for the erythrocyte enzyme glutathion reductase. She had normal values.     

Normal phenotype and slight mental retardation in de novo distal 8p deletion (8pter----8p23.1:)

In this report we present a 9-year-old boy with mental retardation, behavioural problems and terminal deletion of the short arm of chromosome 8(8pter----8p23.1:). In contrast with previously reported patients with larger terminal and interstitial 8p deletions he did not present major phenotypic abnormalities.     

Combined deletion 18q22.2 and duplication/triplication 18q22.1 causes microcephaly,mental retardation and leukencephalopathy

Chromosome 18 abnormalities rank among the most common autosomal anomalies with 18q being the most frequently affected. A deletion of 18q has been attributed to microcephaly, mental retardation, short stature, facial dysmorphism, myelination disorders, limb and genitourinary malformations and congenital aural atresia. On the other hand, duplications of 18q have been associated with the phenotype of Edwards syndrome. Critical chromosomal regions for both phenotypes are contentious. In this report, we describe the first case of an 11-year old male with a combined interstitial duplication 18q22.1, triplication 18q22.1q22.2 and terminal deletion 18q22.2q23 with phenotypic features of isolated 18q deletion syndrome and absence of phenotypic features characteristic of Edwards syndrome despite duplication of the suggested critical region. This report allows for reevaluation of proposed critical intervals for the phenotypes in deletion 18q syndrome and Edwards syndrome.     

Partial duplication of 17p

Summary An inherited partial duplication syndrome of 17p is described. A comparison of the symptoms of a de novo partial duplication of 17p (Latta and Hoo, 1974) and those of our own case seems to indicate a characteristic syndrome. The main features include a small-for-date baby born at full term, small stature, microcephaly, typical facial changes, a heart defect, contractures of different joints, and deformities of the feet. The patients show severe motor and mental retardation.     

Partial deletion of the long arm of chromosome 13 (q32q33.2) associated with mental retardation, choanal atresia and fish mouth

13q deletion syndrome is characterized by mental and motor retardation, craniofacial dysmorphic facial appearance and various congenital malformations. In this article, we present a new case with 13q deletion syndrome phenotypically characterized by fish mouth, choanal atresia and severe mental and motor retardation. In order to determine the certain localization of deleted region high resolution multicolor-banding technique was performed and the karyotype determined as 46,XX,del(13)(q32q33.2). To come in future to a genotype-phenotype correlation, it is very important to delineate the deleted region in such cases in detail by cytogenetic/ molecular cytogenetic methods.     

De novo deletion 7q36 resulting from a distal 7q/8q translocation: phenotypic expression and comparison to the literature

We report on a 6-year-old male patient with de novo 7q36 deletion and 8q24.3 duplication diagnosed by combining traditional G-banding and FISH studies. His clinical history was remarkable for pre- and postnatal growth retardation, neonatal feeding problems and developmental/mental retardation with non-verbal communication. He presented microcephaly, large ears, narrow palpebral fissures with blepharoptosis, epicanthic folds, large depressed nasal bridge, bulbous nasal tip, right cryptorchidism and delayed bone age on X-rays. There was no evidence of holoprosencephaly (HPE) or sacral agenesis sequence. By using in FISH analysis a series of YACs linearly ordered along the 7q36 region, the precise breakpoint on 7q36 was found to be within the target region of the YAC 742G8, a YAC that appeared to be only partially deleted. Clinical and chromosomal findings in this patient are compared to those previously recorded in similarly investigated patients from the literature with terminal 7q deletion.     

Direct transmission of the 18q- syndrome from mother to daughter

A 34-year-old mother presented moderate mental retardation, short stature, microcephaly, and characteristic facial dysmorphism. Her 12-year-old daughter manifested moderate mental retardation, short stature, microcephaly, dysplastic external ear canals, hearing impairment, and characteristic facial dysmorphism. Cytogenetic analysis of the family revealed a normal karyotype, 46,XY, in the father, and a 46,XX,del(18)(q22.2) karyotype in both mother and daughter. Molecular marker analysis determined direct transmission of the distal 18q deletion from mother to daughter. The present case provides evidence of fertility of the affected females and a mother-to-daughter direct transmission in the familial 18q- syndrome. Identification of affected females with the 18q- syndrome should include genetic counseling of possible direct transmission and consideration of birth control or prenatal genetic testing at reproductive age.     

A detailed investigation of two cases exhibiting characteristics of the 6p deletion syndrome

Deletions of the short arm of chromosome 6 are relatively rare, only 16 cases having been described in the literature so far. Here we present a detailed investigation by fluorescence in situ hybridisation of two further cases with different but overlapping interstitial deletions involving 6p22, 6p23 and 6p24. The main features involved are craniofacial malformations, heart and kidney defects, mental retardation/developmental delay, hypotonia and hydrocephalus. By using 36 yeast artificial chromosome and cosmid clones from a contig covering 6p22.3–6p25 and other probes with defined cytogenetic locations within 6p21– 6p22 we have precisely localised the breakpoints involved in each of the cases, estimated the sizes of the deleted regions and defined the region that is hemizygously deleted in both cases. Received: 20 March 1996 / Revised: 13 May 1996     

The E7-associated cell-surface antigen: a marker for the 11p13 chromosomal deletion associated with aniridia-Wilms tumor.

Unbalanced interstitial deletions of the p13 region of human chromosome 11 have been associated with congenital hypoplasia or aplasia of the iris, mental retardation, ambiguous genitalia, and predisposition to Wilms tumor of the kidney. Utilizing somatic cell hybrids containing either the normal or abnormal chromosome 11 from a child with Wilms tumor and aniridia, we previously mapped the E7 cell-surface antigen to the 11p1300-to-11p15.1 region. To localize even further the site of this antigen on chromosome arm 11p, we have produced somatic cell hybrids from the fibroblasts of a second child with Wilms tumor and aniridia and a different deletion of 11p [46,XY, del (11)(pter----p14.1::p11.2----qter)]. Furthermore, the normal and deleted chromosome 11 could also be distinguished on the basis of a restriction fragment length polymorphism for the beta-globin gene. Hybrid cells containing the deleted chromosome were not killed in the presence of complement and the E7 monoclonal antibody (which recognizes E7 cell surface antigen), while hybrid cells containing the patient's normal chromosome 11 were killed. Thus, expression of the E7-associated cell-surface antigen can be mapped to the 11p13 region, and it appears to be a potential marker of the chromosome abnormality associated with aniridia-Wilms tumor.     

Familial occurrence of 18q-

Summary An unusual segregation of the partial long arm deletion of a chromosome 18 is reported. This aberration was found in the feeble-minded mother and in her 4 daughters. The fifth child has XXY-Klinefelter's syndrome. The carriers of 18q — in this family reveal small stature, microcephaly, and mental deficiency in the range from feeble-minded to severe imbecility. Other characteristic features commonly found in patients with 18q — syndrome, as mid-face retraction, downward slanting mouth, heart defect, and atretic ear canals were not observed.     

Partial trisomy 8p (8p11.2-->pTER) and deletion of 13q (13q32-->qTER): case report

We report a female infant with partial trisomy 8p (8p11.2-->pter) and deletion of 13q (13q32-->qter). She was born with mild hypotonia, intrauterine growth retardation, microcephaly, micrognathia, large low set ears, pectus excavatum, anteriorly placed anus, and bilateral clinodactyly. Echocardiography showed left ventricular hypertrophy, bicuspid aortic valve, dilatation of the aorta and pulmonary artery, and prolapse of atrio-venticular valve leaflets. Cytogenetic investigation of her sister and her father showed that the altered region resulted from a balanced translocation between the part of the long arm of chromosome 13 and short arm of chromosome 8. In partial trisomy 8p, the clinical picture of the patients comprises hypotonia, structural brain abnormalities, facial anomalies including a large mouth with a thin upper lip, a high arched palate, a broad nasal bridge, an abnormal maxilla or mandible, malformed, low set ears, and orthopedic anomalies. Although patients with proximal deletions of 13q that do not extend into band q32 have mild to moderate mental and growth delays with variable minor anomalies, patients with more distal deletions including at least part of band q32 usually have major malformations such as retinoblastoma, mental-motor growth retardation, malformation of brain and heart, anal atresia, and anomalies of the face and limbs. To our knowledge partial trisomy 8p and partial monosomy of 13q have not been reported previously in the same person.     

Complete trisomy 17p a relatively new syndrome

A patient with a de novo duplication of 17p is described. A comparison with five other published cases indicates several features in common that seem characteristic of the syndrome. Primary features include, low birth weight, small size, severe mental and motor retardation, heart defect, failure to thrive and peculiar facial traits. The prominent facial features are, a tendency for round and flat mid face, small palpebral fissures, hypertelorism, microcephaly and low set prominent ears.     

A case with de novo interstitial deletion of chromosome 7q21.1-q22

A case with de novo interstitial deletion of chromosome 7q21.1-q22: A patient with multiple congenital anomalies was found to have a de novo proximal interstitial deletion of chromosome 7q21.1-q22. The patient was 10.5 years of age, and manifestations include growth retardation (below 3rd percentile), mental retardation, mild microcephaly, hypersensitivity to noise, mild spasticity, short palpebral fissures, alternant exotropia, compensated hypermetropic astigmatism, hypotelorism, hypoplastic labia majora and minora, clinodactyly of fingers 4 and 5. Molecular studies revealed that the deletion had a paternal origin, while chromosomes of both parents cytogenetically were shown to be normal. Molecular, and fluorescence in situ hybridization (FISH) analyses confirmed no deletion at the Williams-Beuren Syndrome region. Some of the heterogeneous clinical findings were consistent with previously reported cases of same chromosomal breakpoints.     

Molecular cytogenetic characterization of two independent karyotypic anomalies in a patient with severe mental retardation and juvenile idiopathic arthritis

We report on a patient with severe mental retardation, dysmorphic features as well as juvenile idiopathic arthritis. G-banding indicated two independent karyotypic anomalies in this patient: an interstitial deletion del(X)(p21p22.3) and a rearrangement involving chromosomes 1 and 7, which represents a direct insertion, ins(7;1)(q36;p13.2p31.2). Non-random inactivation of the paternally derived del(X) chromosome was observed in blood lymphocytes and fibroblasts. High resolution analysis of the rearrangement involving chromosomes 1 and 7 subsequently revealed the additional submicroscopic deletion of at least 5 Mb at the 1p13.2 breakpoint. The deletion occurred on the paternal chromosome and encompasses the PTPN22 gene, already known to be associated with juvenile idiopathic arthritis. Our findings underline the importance of closely investigating the breakpoint regions of apparently balanced rearrangements in patients with abnormal phenotypes since complex chromosomal rearrangements (CCRs) may turn out to be unbalanced. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.