Chromosome 6q- and associated malformations.

A dysmorphic retarded fourteen-mont-old female with partial deletion of the long arm of chromosome 6 is presented. The breakpoint in 6q was in region 2, probably at band 5. Eight other infants with a deletion involving the long arm of chromosome 6, including five with a ring chromosome 6, have been reported. The affected individuals have in common microcephaly, micrognathia, hypotonia and psychomotor retardation, but do not appear to have a distinctive phenotype.     

Ring chromosome 2: Clinical,chromosomal, and biochemical aspects

Summary A new case of ring chromosome 2 is described and compared with the five cases hitherto reported. The clinical picture includes a severe pre- and postnatal growth failure, microcephaly, psychomotor retardation, and some minor dysmorphic features. Cytogenetic studies revealed a ring 2 structure and aneuploidy. Banding analysis failed to demonstrate a substantial loss of chromosomal material. Enzymologic studies revealed a decrease of red cell acid phosphatase activity suggesting the localization of its gene in the 2p252pter region.     

Siblings with chromosome mosaicism,microcephaly, and growth retardation: the phenotypic expression of a human mitotic mutant?

Summary We report male and female siblings with extreme microcephaly and mental retardation, growth retardation, and multiple chromosome mosaicism. Mental retardation associated with chromosome mosaicism does not always carry a low recurrence risk.     

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.     

Sensorineural deafness in two infants: a novel feature in the 22q distal duplication syndrome. Cardinal signs in trisomies 22 subtypes

Sensorineural deafness in two infants: a novel feature in the 22q distal duplication syndrome. cardinal signs in trisomies 22 subtypes: Distal trisomy 22 has been described in more than 15 individuals. The features are severe mental and growth retardation, failure to thrive, congenital hypotonia, hydrocephalus, microcephaly, cleft palate, epicanthic folds, low-set ears, broad prominent nasal bridge, long philtrum, micrognathia, finger-like thumbs, cryptorchidism. We describe a girl deceased at the age of 12 years and an 11 year old boy, both with a duplication of distal 22q due to a parental pericentric inversion (22) (p13q12). Their phenotypes are compatible with distal trisomy of chromosome 22. However, they did not present cleft palate, but the survival of both patients permitted us to discover sensorineural deafness not previously reported in this chromosomal duplication.     

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.     

Ring chromosome 17 in a mentally retarded boy.

A six-year-old boy was found to have a ring chromosome 17. In addition to psychomotor retardation, speech delay and seizure disorders, his abnormal phenotypic features included epicanthal folds, broad depressed nasal bridge, protruding thick upper and lower lips, micrognathia, narrow high arched palate, short fifth fingers with a mild degree of clinicodactyly, multiple café-aui-lait spots, and abnormal dermatoglyphics.     

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.     

Microcephaly, microphthalmia, congenital cataract, with calcification of the basal ganglia: MCA/MR syndrome

We present a Hungarian girl with microcephaly, microphthalmia, congenital cataract, prominent nasal root, peaked nose, micrognathia with high arched palate, mild mental retardation, calcification of the basal ganglia and serology for the connatal infections. We suggest that our proband may be an allelic variant of COFS syndrome.     

Valproic acid and lamotrigine treatment during pregnancy: The risk of chromosomal abnormality

A baby born to an epileptic mother had dysmorphological features associated with 47,XXX karyotype. The mother had been treated with valproic acid (1800 mg per day) and lamotrigine (100 mg per day) throughout pregnancy. Dysmorphological features detected in baby were intrauterine growth retardation, hypertelorism, flattened nasal bridge, low set malformed auriculas, micrognathia, very small an bow-shaped mouth with thin upper lip, cleft palate, arachnodactyly, camptodactyly, secundum atrial septal defect, bilateral hammer toes and decreased creases on the soles. At 6 months old she showed motor retardation. The molecular analysis of parents revealed that extra X chromosome was inherited from the mother. In this case whether the dysmorphological features and 47,XXX karyotype were caused by lamotrigine and valproic acid treatment during pregnancy or coincidence is in question.     

Delineation of the critical deletion region for congenital heart defects, on chromosome 8p23.1

Deletions in the distal region of chromosome 8p (del8p) are associated with congenital heart malformations. Other major manifestations include microcephaly, intrauterine growth retardation, mental retardation, and a characteristic hyperactive, impulsive behavior. We studied genotype-phenotype correlations in nine unrelated patients with a de novo del8p, by using the combination of classic cytogenetics, FISH, and the analysis of polymorphic DNA markers. With the exception of one large terminal deletion, all deletions were interstitial. In five patients, a commonly deleted region of approximately 6 Mb was present, with breakpoints clustering in the same regions. One patient without a heart defect or microcephaly but with mild mental retardation and characteristic behavior had a smaller deletion within this commonly deleted region. Two patients without a heart defect had a more proximal interstitial deletion that did not overlap with the commonly deleted region. Taken together, these data allowed us to define the critical deletion regions for the major features of a del8p.     

Distal 19q duplication

Summary Two brothers with a distal 19q duplication due to a maternal balanced reciprocal translocation were observed. Clinical features included intrauterine and postnatal growth retardation, microcephaly, and mental retardation with seizures. Dysmorphic facies consisted of coarse hair with a high frontal hairline, short philtrum and nose, flat nasal root, and a broad mouth with downturned commissures. Both routine G-banded and high-resolution prometaphase chromosome studies were employed in evaluation of the family. The dysmorphic features and karyotypes of the affected brothers are compared with those of the two previously reported families with 19q duplication, and a common distal-19q phenotypes is suggested.     

Valproic acid and lamotrigine treatment during pregnancy. The risk of chromosomal abnormality

A baby born to an epileptic mother had dysmorphological features associated with 47,XXX karyotype. The mother had been treated with valproic acid (1800mg per day) and lamotrigine (100mg per day) throughout pregnancy. Dysmorphological features detected in baby were intrauterine growth retardation, hypertelorism, flattened nasal bridge, low set malformed auriculas, micrognathia, very small an bow-shaped mouth with thin upper lip, cleft palate, arachnodactyly, camptodactyly, secundum atrial septal defect, bilateral hammer toes and decreased creases on the soles. At 6 months old she showed motor retardation. The molecular analysis of parents revealed that extra X chromosome was inherited from the mother. In this case whether the dysmorphological features and 47,XXX karyotype were caused by lamotrigine and valproic acid treatment during pregnancy or coincidence is in question.     

Partial trisomy 3q in a child with sacrococcygeal teratoma and Cornelia de Lange syndrome phenotype

Partial duplication of 3q is a rare chromosomal disorder that leads to multiple congenital abnormalities such as growth retardation, microcephaly and characteristic facial features. Although the phenotype of the patient has similarities with Cornelia de Lange Syndrome they are etiologically different. We report here a 9 months old baby boy with partial duplication of 3q and features similar with Cornelia De Lange syndrome. Conventional cytogenetic analysis revealed a derivative chromosome 21. In order to determine the origin of this chromosome region we used subtelomeric FISH technique. Based on the results of all these cytogenetic studies and the physical examinations, the diagnosis is partial 3q duplication.     

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.     

ATFresno: a phenotype linking ataxia-telangiectasia with the Nijmegen breakage syndrome.

This report describes twin girls with typical features of ataxia-telangiectasia, including increased alpha-fetoprotein, radio-resistant DNA synthesis, characteristic chromosome abnormality, and immunodeficiency. They have, in addition, microcephaly and mental retardation. Complementation studies were performed utilizing Sendai virus--mediated fusion of fibroblast cell lines. Complementation was observed with patients in ataxia-telangiectasia complementation groups A, C, and E but not with the cell line from a patient with the Nijmegen breakage syndrome, in which patients have microcephaly, radio-resistant DNA synthesis, chromosome aberrations, and immunodeficiency but lack ataxia and telangiectasia. These data suggest that the Nijmegen breakage syndrome and the patients described here are not genetically distinct entities but form a spectrum of one disorder.     

Ring chromosome 15 in child with a minor dysmorphism of phenotype

Summary The analysis of a karyotype of a girl with slight mental retardation, without significant dysmorphism, showed the presence of a ring chromosome in group 13–15. By the application of G technique it was discovered that in this case it was an aberrant chromosome 15.Besides retardation in growth and a slight mental backwardness in this case, it was confirmed that in cases of ring 15 syndrome no preponderant change appears in phenotype.     

Ring chromosome 18 in a child with febrile seizures

Ring chromosomes are uncommon cytogenetic findings but have meanwhile been reported for nearly all human chromosomes. Among the rare observations of ring chromosomes in man, the diagnosis of ring chromosome 18 represents a prominent group. We here describe on the cytogenetic analysis results obtained for a 9 years old male patient of non-consanguineous parents. He had growth and developmental delay, mental and motor retardation, microcephaly, microphtalmia, triangle face, small dysplastic ears, strabismus, epicanthal folds on the left, short stature, cryptorchidism, spasticity, pes equinovarus, pes planus, hypothroidism, stereotypic movements and febrile seizures. Also he had hypomyelinization and multiple hyperintense focuses within the white matter on the MRI. The generalized epileptiform abnormality originated from bilateral Centroparietal region. The metabolic investigations including blood and urine amino acids and lysosomal screening tests were normal. The chromosome analysis identified [46,XY,r(18)/46,XY] in 35% of cells a ring 18 and in 65% of cells normal karyotype in peripheral blood cells examined by standard G-bands by Trypsin using Giemsa (GTG) analysis. The dysmorphic features of the presented patient are discussed to the identification of the genotype-phenotype correlation related to his karyotype.     

A child with mosaicism for deletion (14)(q11.2q13)

In this case report we describe a child with a de novo deletion in the (q11.2q13) region of chromosome 14. The child presented with dysmorphic features - anophthalmia, microcephaly, and growth retardation. Cytogenetic studies showed mosaicism. The karyotype was 46,XX,del(14)(q11.2;q13) [16] /46,XX [9]. We compared the features observed in this child with that of others with the same deletion reported in scientific literature and found that this is the first report of a child mosaic for this deletion. It is also the first time it has been reported in association with anophthalmia.     

Familial ring (20) chromosomal mosaicism

Summary Ring (20) chromosomal mosaicism defined by two cell lines (one normal and the other with the ring) has been demonstrated in lymphocyte and fibroblast cultures from three members of a family through two generations. Two carriers of the ring chromosome were affected and showed the typical signs of r(20) syndrome including mental retardation, microcephaly, behavioral disorders, and epilepsy. The epilepsy is characterized by complex partial seizures sometimes evolving secondarily into generalized tonic-clonic seizures and is poorly controlled by or resistant to medical treatment. The mother of the two patients, also a carrier of ring (20) chromosomal mosaicism, was clinically and phenotypically normal and did not exhibit any signs of epilepsy. Lymphocyte and fibroblast cultures from the most severely affected sib, the proband, contained the highest percentage of cells with ring (20) chromosome and revealed the greatest instability of the ring. Though it is assumed that the ring (20) chromosome arose from terminal breakage and reunion in both arms, no loss of genetic material could be documented cytogenetically. Yet the question arises of how ring chromosomal mosaicism can be passed on. One explanation might be that a chromosome 20 predisposed to terminal lesions or breaks is transmitted from the mother to her offspring. Inherited instability of this type might lead to de novo formation of the ring.