Monosomy 6q1: Syndrome delineation

We report on a girl with a de novo 6q1 interstitial deletion. To our knowledge, this is the second reported case with a deletion of 6q11–q15. We review the phenotype of monosomy 6q1. Our patient has manifestations similar to others with monosomy 6q1 including mental deficiency, growth retardation, short neck, and minor facial anomalies. © 1996 Wiley-Liss, Inc.     

Recognizable behavioral and somatic phenotype in patients with proximal interstitial 18q deletion: Report on a new affected child and follow-up on the original reported familial cases

We describe a moderately retarded boy with a chromosome 18 deletion involving the regions q11.2q12.2. His phenotype is similar to that of other reported cases of proximal interstitial deletions involving 18q. We also provide follow-up information on the first 4 cases of proximal interstitial deletion of 18q from a family with a complex chromosome rearrangement originally reported in 1974. © 1992 Wiley-Liss, Inc.     

6q1 monosomy: a distinctive syndrome

A female infant with a de novo del 6q14q16.2 and five other patients with del 6q1 reported in the literature allow the delineation of a characteristic syndrome, the main features of which are: severe mental retardation, a round face with full cheeks, upslanting palpebral fissures, a short neck, umbilical hernia, malpositioned feet with syndactyly II-III, and typical dermatoglyphics with an excess of whorls and clinodactyly of the Vth finger.     

Proximal interstitial 6q deletion: A recognizable syndrome

We report on an 8-year-old boy with a proximal interstitial deletion of the long arm of chromosome 6 with breakpoints q13 to q14.2. He has a characteristic facial appearance that is seen in several of the previously described cases. Details of his clinical course are reviewed and compared with the nine previous reported cases of the proximal deletion 6q syndrome. Am. J. Med. Genet. 71:353–356, 1997. © 1997 Wiley-Liss, Inc.     

Monosomy 21q: two cases of del(21q) and review of the literature

We report on two cases of partial monosomy 21 and review cases with a partial or an apparently full monosomy 21. In situ hybridization and/or molecular studies appear to be necessary tools to study imbalance in such a small chromosome and to perform further genotype-phenotype correlations. The segregation mode in cases with a translocation is adjacent 1, adjacent 2, and 3:1 in about 1/4, 1/4, and 1/2 of the cases, respectively.     

Duplication 6q21q23 in two unrelated patients

We report on two patients with rare 6q duplications. The karyotype of patient 1 is 46,XY,dup(6)(q21q23.3). The karyotype of patient 2 is 46,XX,dup(6)(q21.15q23.3). These two patients have some nonspecific physical findings in common including a depressed nasal bridge, epicanthal folds, mild heart defects, and developmental delay, but each had other congenital anomalies. Am. J. Med. Genet. 80:112–114, 1998. © 1998 Wiley-Liss, Inc.     

De novo interstitial deletion q16.2q21 on chromosome 6

A de novo interstitial deletion of 6q16.2q21 was observed in a 23-month-old boy with mental and psychomotor delay, obese appearance, minor craniofacial anomalies, and brain anomalies. We compare clinical manifestations of this patient with those observed in previously reported cases with similar 6q interstitial deletions. It is interesting to note the clinical similarities between some patients with interstitial deletions of 6q16 or q21 bands and patients with Prader-Willi syndrome (PWS) and it may help to keep in mind cytogenetic studies of patients with some PWS findings. © 1995 Wiley-Liss, Inc.     

New insights into the phenotypes of 6q deletions

Deletions of chromosome 6q are rare. We report 3 new patients with 6q deletions. Case 1 is a male with an interstitial deletion [del(6)(q13q14.2)], hypotonia, speech delays, and minor anomalies. Case 2 is a male with an interstitial deletion [del(6)(q16.2q22.32)] and malformations, including truncus arteriosus and bilateral oligodactyly. Case 3 is a male with a terminal deletion [del(6)(q25.2)] with retinal pits, hydrocephalus, atrioventricular canal, and hydronephrosis. The findings in our patients and those from 57 previously reported cases demonstrated 3 phenotypic groups associated with 6q deletions. Group A [del(6)(q11–q16)] had a high incidence of hernias, upslanting palpebral fissures, and thin lips with lower frequency of microcephaly, micrognathia, and heart malformations. Group B [del(6)(q15–q25)] was associated with increased intrauterine growth retardation, abnormal respiration, hypertelorism, and upper limb malformations. Group C [del(6)(q25-qter)] was associated with retinal abnormalities, cleft palate, and genital hypoplasia. The only universal finding among all patients with 6q deletions was mental retardation. Other findings common to all 3 groups included ear anomalies (90%), hypotonia (82%), and postnatal growth retardation (68%). Am. J. Med. Genet. 70:377–386, 1997. © 1997 Wiley-Liss, Inc.     

Application of fluorescence in situ hybridization for early prenatal diagnosis of partial trisomy 6p/monosomy 6q due to a familial pericentric inversion

Wauters JG, Bossuyt PJ, Roelen L, van Roy B, Dumon J. Application of fluorescence in situ hybridization for early prenatal diagnosis of partial trisomy 6p/monosomy 6q due to a familial pericentric inversion. Clin Genet 1993: 44: 262–269. © Munksgaard, 1993
We report the prenatal diagnosis of a karyotype 46,XY,rec(6)dup p, inv(6) (p23q27) mat detected by fluoroscence in situ hybridization using chromosome 6pter and 6qter specific DNA markers. This partial duplication-deletion (6p12→pter; 6q27→qter) emanated from a balanced pericentric inversion 46,XX inv(6) (p23q27)pat present in the mother. The phenotypes of two relatives with the same unbalanced anomaly are described. This report illustrates the sensitivity and specificity of fluorescence in situ hybridization (FISH) and its benefit in rapid and unequivocal prenatal diagnosis of subtle chromosomal rearrangements.     

Autism and maternally derived aberrations of chromosome 15q

Of the chronic mental disabilities of childhood, autism is causally least well understood. The former view that autism was rooted in exposure to humorless and perfectionistic parenting has given way to the notion that genetic influences are dominant underlying factors. Still, identification of specific heritable factors has been slow with causes identified in only a few cases in unselected series. A broad search for genetic and environmental influences that cause or predispose to autism is the major thrust of the South Carolina Autism Project. Among the first 100 cases enrolled in the project, abnormalities of chromosome 15 have emerged as the single most common cause. The four abnormalities identified include deletions and duplications of proximal 15q. Other chromosome aberrations seen in single cases include a balanced 13;16 translocation, a pericentric inversion 12, a deletion of 20p, and a ring 7. Candidate genes involved in the 15q region affected by duplication and deletion include the ubiquitin-protein ligase (UBE3A) gene responsible for Angelman syndrome and genes for three GABA_A receptor subunits. In all cases, the deletions or duplications occurred on the chromosome inherited from the mother. Am. J. Med. Genet. 76:327–336, 1998. © 1998 Wiley-Liss, Inc.     

Familial complex chromosomal rearrangement resulting in duplication/deletion of 6q1c to 6q16

A familial complex chromosomal rearrangement (CCR) was ascertained through a mentally retarded, dysmorphic individual. Carriers of the CCR have the karyotype 46,XX or XY, t(6;15)(q16;q21), ins(3;6)(q12;q14q16), and malsegregation of the CCR resulted in loss of the segment 6q14 to 6q16 in the proband, and in an additional copy of the same segment in three members of the extended family. The proband has features similar to other reported cases with deletion of 6q1. The individuals with duplication of 6q14 to 6q16 have moderate mental retardation, short stature, obesity, microcephaly, brachycephaly, a short smooth philtrum, central hair whorl, simian creases, 5th finger brachydactyly and skeletal disproportion. In the 4-generation family, CCR carriers have a 20% empiric risk of phenotypically abnormal livebirths.     

Proximal 7q interstitial deletion in a severely mentally retarded and mildly abnormal infant

We describe a boy with an interstitial deletion of 7q [46,XY,del(7)(pter→q11.21::q11.23→qter)] and severe mental retardation, bilateral inguinal hernias, plagiocephaly, and mildly abnormal facial appearance. This is the 21st case report involving a proximal 7q deletion, but the first report of this specific deletion in the absence of Zellweger syndrome. Specific genotype-phenotype correlations are still not possible for this region of chromosome 7. © 1992 Wiley-Liss, Inc.     

Mild “duplication 6q syndrome”: A case with partial trisomy (6)(q23.3q25.3)

We report on a female infant with partial 6q trisomy (46,XX,dir dup(6)(q23.3q25.3)) and phenotypic characteristics of the “duplication 6q syndrome,” including intrauterine growth retardation, dolichocephaly, depressed nasal bridge, almond-shaped palpebral fissures, short neck, flexion-contractures of the wrists, and mild generalized hypertonia. Although clearly belonging to the described “duplication 6q syndrome,” her features were milder than those found in the literature. Comparison of the phenotype of this child with other published reports indicates that specific phenotypic components of the duplication 6q syndrome cannot be attributed to duplication of a specific band or bands on 6q. Am. J. Med. Genet. 68:450–454, 1997. © 1997 Wiley-Liss, Inc.     

Congenital anomalies and anthropometry of 42 individuals with deletions of chromosome 18q

Deletions of chromosome 18q are among the most common segmental aneusomies compatible with life. The estimated frequency is approximately 1/40,000 live births [Cody JD, Pierce JF, Brkanac Z, Plaetke R, Ghidoni PD, Kaye CI, Leach RJ. 1997. Am. J. Med. Genet. 69:280–286]. Most deletions are terminal encompassing as much as 36 Mb, but interstitial deletions have also been reported. We have evaluated 42 subjects with deletions of 18q at our institution. This is the largest number of individuals with this chromosome abnormality studied by one group of investigators. Here we report the physical findings in these individuals. We have compared our findings with those of previously reported cases and have found a significantly different incidence of several minor anomalies in our subjects. We also describe here several anomalies not previously reported in individuals with deletions of 18q, including short frenulum, short palpebral fissures, disproportionate short stature, overlap of second and third toes, and a prominent abdominal venous pattern. Characteristics found in subjects were analyzed for correlation with cytogenetic breakpoints. Several traits were found to correlate with the extent of the deletion. Large deletions were associated with significantly decreased head circumference and ear length as well as the presence of proximally placed and/or anomalous thumbs. Individuals with the smallest deletions were more likely to have metatarsus adductus. Although relatively few genotype/phenotype correlations were apparent, these data demonstrate that correlations with breakpoint are possible. This implies that more correlations will become evident when the more precise molecularly based genotyping is completed. These correlations will identify critical regions on the chromosome in which genes responsible for specific abnormal phenotypes are located. Am. J. Med. Genet. 85:455–462, 1999. © 1999 Wiley-Liss, Inc.     

Interstitial 6q deletion and Prader-Willi-like phenotype

A third case of an interstitial deletion of the long arm of chromosome 6 with clinical features mimicking Prader-Willi syndrome (PWS) is presented. Although preliminary clinical evaluation in each case suggested PWS, further review revealed that the features in all three cases are not completely compatible with the characteristic findings in Prader-Willi syndrome. Furthermore, the deletions in the three cases do not show a consistent region of overlap. Consequently, no particular band or region in 6q can be defined as associated widi obesity. However, our findings confirm the suggestion of Villa et al. in 1995, that individuals with a PWS phenotype who are cytogenetically and molecularly negative for a deletion of 15q11-q13 should be examined for a deletion of 6q.     

Ocular albinism in a male with del (6)(q13–q15): Candidate region for autosomal recessive ocular albinism?

We describe a boy with an interstitial deletion of 6(q13–q15) and include “coarse” facial features, upslanting palpebral fissures, thin vermilion border of the upper lip, elongated philtrum, developmental delay, and profound hypotonia. The child's eye findings, pedigree, paucity of maternal ocular changes, and lack of melanin macroglobules in the skin suggest that this individual's phenotype is clinically similar to that of autosomal recessive ocular albinism. Though it is possible that this deletion and his ophthalmic disorder are coincidental, we postulate that the ocular albinism may be due to hemizygosity for a paternally derived ocular albinism gene located on chromosome 6 in the region q13–q15. This patient's deletion is secondary to a recombination of a maternal intrachromosomal inverted insertion of this region. Of the 7 reported 6q1 deletions, this is the only case that is due to a familial chromosome rearrangement.     

A de novo 6q11—q15 duplication investigated by chromosome painting

A de novo interstitial duplication of the 6q11—q15 chromosome region, confirmed by the application of a chromosome 6 painting probe, was observed in a patient with craniofacial dymorphism, psychomotor retardation, cryptorchidism and hypospadias. Despite the publication of several cases showing partial trisomy 6q, to our knowledge the duplication of the proximal region q11-q15 has not previously been reported.