Fertility and the cri du chat syndrome

We describe a mother and daughter with typical cri du chat syndrome. Previous investigators have noted the lack of information about the reproductive fitness of patients with this disorder. This report demonstrates that females with cri du chat syndrome are fertile, can gestate and likewise deliver affected offspring, which has significant management and counseling implications.     

A neuropsychological-genetic profile of atypical cri du chat syndrome: implications for prognosis

Cri du chat syndrome is associated with a deletion on the short arm of chromosome 5. The main diagnostic feature is a high pitched, cat-like cry which has recently been localised to 5p15.3 and is separate from the remaining clinical features of the syndrome, which have been localised to 5p15.2. The present study describes a family of four who have a deletion slightly distal (5p15.3) to the critical region. Detailed neuropsychological evaluations indicated a similar pattern of cognitive performance to that reported for subjects with typical CDCS but with only minimal intellectual impairment. In addition, in this family the 5p deletion is transmitted in an autosomal dominant fashion, contrasting with most cases of CDCS, which are either de novo or occur as an unbalanced product of a balanced translocation in a normal parent. This study confirms the importance of differentiating between 5p deletions that coincide with the typical cri du chat phenotype which includes severe to profound learning disability and deletions that only delete the distal critical region that coincides with a milder degree of cognitive impairment and a much improved prognosis.     

5p;12q translocation with manifestations of cri du chat syndrome and Marfanoid arachnodactyly

A 12-year-old boy with a history of a mewing cry after birth, severe mental retardation, Marfanoid arachnodactyly, general osteomalacia and multiple bone fractures was found to have a de novo 5p;12q chromosomal translocation. The karyotype is 46,XY,t(5;12)(12qter----12q24.1::5p15----cen----5qt er; 12pter----cen----12q24.1). The karyotypes of other examined family members are normal. The manifestations of cri du chat syndrome are explained by the loss of a small segment of 5p15 which is responsible for the major stigmata of the syndrome, and the abnormalities of the osseous system may be the results of untreated vitamin D resistant rickets.     

Prenatal detection of cri du chat syndrome on uncultured amniocytes using fluorescence in situ hybridization (FISH)

Fluorescence in situ hybridization (FISH) with a chromosome-region-specific DNA probe was used prospectively on uncultured amniocyte interphase cells to detect an unbalanced chromosome abnormality that resulted in cri du chat or 5p – syndrome. Confirmation was performed by routine cytogenetics.     

Cri du chat syndrome due to meiotic recombination in a pericentric inversion 5 carrier

A female infant presented at birth with hypotonia, growth retardation, distinctive facies, multiple congenital anomalies, and a high-pitched mewing cry characteristic of cri du chat syndrome. Chromosome studies from both peripheral blood and fibroblasts showed a 46,XX,5p- karyotype. Parental chromosome studies revealed that the mother carried an apparently balanced pericentric inversion of one chromosome no. 5, 46,XX,inv(5)(p14q35). Meiotic crossing-over in the mother within the inverted segment of chromosome 5 gave rise to the unbalanced karyotype, 46,XX,rec(5)dup q, inv(5)(p14q35)mat in the infant. A small terminal segment of the long arm of chromosome 5 (q35-pter) is duplicated with a deletion of the short arm of chromosome 5 (p14-pter), accounting for the features of cri du chat syndrome. Fewer than 1 in 200 of cri du chat syndrome cases are due to recombination aneusomy arising from a parental inversion of chromosome 5. Some of these cases, however, do not have typical cri du chat syndrome, reflecting significant duplication of 5q material. These cases are reviewed with the present case, and recombination behaviour leading to chromosome imbalance is discussed.     

Anthropometry in the Cri du Chat syndrome

Anthropometric and cranial X-ray measurements of 35 individuals with a 5p- karyotype showed a general growth retardation. Height, weight, circumference of the thorax, pelvic breadth, and the size of the skull, face, hands and feet were all subnormal. Only the inner canthal distance was moderately increased, especially in young individuals, but there was no true hypertelorism. The palate was not high-arched. Large and small terminal deletions produced much the same anthropometric features; and the proband's sex did not have a major influence. Age variations within parameters examined followed the developmental pattern of normal individuals. A certain phenotypical variation in the Cri du Chat syndrome may therefore be attributed to normal changes or to intrapersonal conditions.     

Growth charts for cri‐du‐chat syndrome: An international collaborative study

Low birth weight and slow growth are frequently observed in the patients with cri‐du‐chat syndrome. To provide a growth reference standard for children with cri‐du‐chat syndrome, syndrome‐specific growth charts have been developed from a combination of cross‐sectional and longitudinal measurements on 374 patients from North America, Italy, Australia, and the British Isles. The data were obtained from pediatric records, parent reporting, and personal examinations at national 5p‐ parent support group meetings in the U.S., Italy, U.K., and Australia. The growth curves include height and weight measurements for patients ages 0 to 18 years and head circumference measurements for patients ages 0 to 15 years. Birth weight was above the 5th percentile of general population in 50% of cases: mean weight 2.8 kg ± 1.85 SD for males and 2.6 kg ± 1.51 SD for females. Growth curve medians were usually at or below the 5th centile of reference populations throughout life. The median head circumference falls below the 2nd centile, and this change increases with age. The charts show that compared with the standard population, most children with cri‐du‐chat syndrome are small at birth and as they grow most, but not all, have significant microcephaly and compromised weight for age, and to a lesser extent, compromised height for age. Am. J. Med. Genet. 94:153–162, 2000. © 2000 Wiley‐Liss, Inc.     

Cri du chat syndrome determined by the 5p15.3-->pter deletion--diagnostic problems

A cytogenetic analysis was performed on an 8-day-old girl, who was suspected of Cri du chat syndrome (CdCS) on the basis of a cat-like cry, despite her dysmorphic features not being characteristic of this syndrome. The cytogenetic analysis revealed a partial deletion of the short arm of chromosome 5, but did not allow precise specification of the break points. Fluorescence in situ hybridization (FISH) analysis, using the specific probe for CdCS, revealed two signals in all the cells analyzed. However, one of two signals was less intense than the other. Thus, telomere probes were applied for all chromosomes. Two signals from 5q and one signal from 5p were observed. The results allowed us to establish the location of the deleted fragment as 5p15.3-->5pter [46,XX,del(5)(p15.3)]. The analysis of a genotype-phenotype correlation confirmed that the cat-like cry, but not the characteristic dysmorphic features of CdCS are correlated with the deletion of 5p15.3.     

Phenotypic and phoniatric findings in mosaic cri du chat syndrome

We report on mosaic 46,XY/46,XY,del(5)(p15) cri du chat syndrome. The clinical findings are compared with those compiled from a literature survey. A phoniatric evaluation was performed and compared with that of a cri du chat patient without mosaicism previously observed by the authors.     

Cri-du-chat syndrome in a child with a 5/15 translocation and interstitial centromeric heterochromatin

A child is described with most of the typical clinical features of the cri-du-chat syndrome. G- and C-banding studies revealed the karyotype 45,XX, -5, -15, +tdic (5;15) with the loss of short arm material from chromosome 5. Centromeric heterochromatin of the translocated No. 15 is still present in the translocation chromosome. However, no silver precipitation after AgNO3-staining was observed on the translocation chromosome, thus indicating a loss or genetic inactivation of the NOR-region of the translocated No. 15. These cytogenetic results and their possible relationship to the cri-du-chat phenotype are discussed.     

Y autosome translocation and complex chromosome rearrangement in cri du chat syndrome.

An unbalanced Y autosome translocation t(5;Y) and an apparently balanced translocation t(2;13) are identified with the Q and R banding in a 7-year-old boy with severe encephalopathy and a multiple malformation syndrome. At birth, the clinical diagnosis of 'cri du chat' syndrome based on the characteristic crying was not confirmed after karyotyping, using conventional staining techniques.     

Molecular approach to analyzing the human 5p deletion syndrome,cri du chat

DNA unique or low-copy fragments were isolated from a genomic DNA library specific for the short (p) arm of human chromosome 5. These chromosome 5p-specific DNA fragments were used to analyze, by Southern blot experiments, somatic cell hybrids that retained either a normal chromosome 5 homolog or a homolog with a partial deletion of 5p, which was derived from either of two persons with the common human deletion syndrome, cri du chat or 5p^– syndrome. In these studies, two classes of DNA fragments were identified, those located outside the region deleted in the persons with cri du chat and those located within the deleted region. This latter class of DNA probes will help to define, at the molecular level, a region of 5p that is critical in producing the phenotype associated with the cri du chat syndrome.     

Childhood apraxia of speech without intellectual deficit in a patient with cri du chat syndrome

We report an 11-year-old girl for whom the diagnosis of cri du chat syndrome (CdCS) was made during a genetic investigation of childhood apraxia of speech. The patient presented with the classic chromosome 5 short arm deletion found in CdCS. The microdeletion, characterised using aCGH (array Comparative Genomic Hybridisation), was 12.85 Mb, overlapping the 5p15.2 and 5p15.3 critical regions. CdCS is typically associated with severe mental retardation while this patient had normal intellectual performance, confirmed by normal results from categorisation tasks. This mild phenotype was assessed using a comprehensive cognitive battery. Language evaluation showed normal receptive vocabulary scores, in contrast with obvious oro-facial dyspraxia. Disabled fine motor skills were confirmed as well as weak visuo-spatial reasoning abilities. In conclusion, fine cognitive assessment may be worthwhile for patients with CdCS since good intellectual functioning may be masked by severe speech and gestural dyspraxia, thus requiring specific teaching and rehabilitation strategies.     

Terminal deletion of the short arm of chromosome 5

Three cases of deletion of the short arm of chromosome 5 are described: one family cluster, in which the mother and three sons are affected, and two sporadics without the typical "cri du chat" phenotype (the family and Case 2 were previously reported in 1982). Mental retardation varied between affected members of the same family. Band p15.2 appears critical for the development of the complete phenotype. A peculiar deafness observed in the familial and one of the sporadic cases suggests a cochlear malformation.     

Clinical and molecular characterisation of 80 patients with 5p deletion: genotype-phenotype correlation

The majority of deletions of the short arm of chromosome 5 are associated with cri du chat syndrome (CdCS) and patients show phenotypic and cytogenetic variability. To perform a genotype-phenotype correlation, 80 patients from the Italian CdCS Register were analysed. Molecular cytogenetic analysis showed that 62 patients (77.50%) had a 5p terminal deletion characterised by breakpoint intervals ranging from p13 (D5S763) to p15.2 (D5S18). Seven patients (8.75%) had a 5p interstitial deletion, four (5%) a de novo translocation, and three (3.75%) a familial translocation. Of the remaining four patients, three (3.75%) had de novo 5p anomalies involving two rearranged cell lines and one (1.25%) had a 5p deletion originating from a paternal inversion. The origin of the deleted chromosome 5 was paternal in 55 out of 61 patients (90.2%). Genotype-phenotype correlation in 62 patients with terminal deletions highlighted a progressive severity of clinical manifestation and psychomotor retardation related to the size of the deletion. The analysis of seven patients with interstitial deletions and one with a small terminal deletion confirmed the existence of two critical regions, one for dysmorphism and mental retardation in p15.2 and the other for the cat cry in p15.3. Results from one patient permitted the cat cry region to be distally narrowed from D5S13 to D5S731. Furthermore, this study lends support to the hypothesis of a separate region in p15.3 for the speech delay.


Keywords: cri du chat syndrome; 5p deletion; phenotype-genotype correlation; FISH     

5p14 deletion associated with microcephaly and seizures

We report on a father and son who have an interstitial deletion of 5p14. The father is clinically and mentally normal while the son has significant clinical involvement including microcephaly, seizures, and global developmental delay. The extent of the 5p14 deletion was determined using fluorescence in situ hybridisation (FISH). The deletion in this present family is smaller than a deletion previously described in a multigenerational family that lacks any clinical phenotype. This report shows that a 5p14 deletion does not always lead to a normal phenotype.