Mark W. Steele

The cri du chat syndrome in adolescents and adults: clinical finding in 13 older patients with partial deletion of the short arm of chromosome No. 5(5p-).

This study of patients aged 12 to 55 years clarifies the course of development of the 5p- syndrome. The catlike cry disappears and new features appear including strabismus, thin face, dental malocclusion, short metacarpals or metatarsals, scoliosis, small wings of the ilia, pes planus, and prematurely gray hair. Mental retardation is severe but general health good. Two of the 13 patients died and brain findings at autopsy are reported.

A simplified six-item checklist for screening for fragile X syndrome in the pediatric population

OBJECTIVE In our general experience, about 2% of samples referred for fragile X testing showed positive results on Southern blot analysis. The aim of this project was to determine whether screening criteria could be developed to increase the proportion of positive test results without sacrificing sensitivity. STUDY DESIGN We retrospectively analyzed nine clinical characteristics from patient records of 273 male and 62 female pediatric probands (average age, 5.7 years) referred for fragile X testing. The characteristics included mental retardation, family history of mental retardation, large or prominent ears, elongated face, attention deficit hyperactivity disorder, autistic-like behavior, simian crease, macroorchidism, and hyperextensible joints. These were scored as 2 if present, 1 If borderline present, and 0 if absent. RESULTS Analysis of the nine characteristics identified three (simian crease, macroorchidism, and hyperextensible joints) with low frequency and statistical insignificance, which were therefore eliminated. With the use of the remaining six characteristics, If a score of 5 or more was used as the criterion for requesting fragle X testing, then close to 60% of those tests from our patient population could have been eliminated without missing any positive cases. The validity of our threshold score of 5 was subsequently confirmed among an additional six cases of fragile X syndrome. CONCLUSION With our simplified six-item clinical checklist, 60% of testing could have been eliminated, thereby improving the cost-effectiveness of fragile X testing and increasing the proportion of cases with positive results by threefold.

Meiotic consequences of an intrachromosomal insertion of chromosome No. 1: a family pedigree

In three generations of the probands patrilineal relatives, 14 subjects were found to be carriers of a “shift” insertional chromosome No. 1 (46, XX or XY, ins(1)(p32q25q31)). The proband and three female relatives, who were mild to moderate mental retardates with minor congenital anomalies, were trisomic for the insertional segment, (1)q25q31. Another subject, who was a markedly immature female abortus with congenital abnormalities, was found to be monosomic for this same chromosomal segment. The cytogenetic evidence suggests that each of these unbalanced recombinant progeny was the result of a single crossing over in the noninsertional loop of a paternal pachytene bivalent of the balanced insertional chromosome No. 1.

Broad-Spectrum Möbius Syndrome Associated with a 1;11 Chromosome Translocation

The authors report a case of Möbius syndrome with Poland syndrome, cleft palate, dextrocardia, mandibular hypoplasia, and multiple areas of diffuse brain volume loss. Karyotype demonstrated a t(1;11)(p22;p13) translocation in the patient and his phenotypically normal father and brother. This case extends the spectrum of congenital disorders that are associated with Möbius syndrome and raises the possibility of genetic heterogeneity for the Möbius disorder.

The Fragile X Marker and Autism in Perspective

Recent reports link the fragile X chromosome abnormality to autism, with the association ranging from 0 to 53%, but the diagnostic criteria for autism were unclear in some of the studies. The need for fragile X chromosome studies in larger populations of autistic children and adults was recognized. In this study, chromosome analyses were performed on 85 carefully diagnosed autistic males, yielding a 2.4% incidence of the fragile X abnormality. It is concluded that the incidence of the fragile X chromosome abnormality in autistic individuals is likely the same as that in the mentally retarded male population and therefore does not increase the risk for autism above that of mental retardation itself.

Trisomy of chromosome 20

A neonate with unusual facial features and multiple congenital malformations expired at 4 hours of age. An autopsy revealed severe anomalies of the gastrointestinal system and spinal dysplasia. Cytogenetic evaluation of fibroblasts cultured from a lung biopsy revealed a karyotype of 47, XX,+20.

Risk effect of maternal age in Pallister i(12p) syndrome

Pallister syndrome is consequent to mosaicism for i(12p). The isochromosome is found mainly in skin fibroblast cultures, but rarely also in cultured peripheral blood lymphocytes. Maternal age for reported cases of Pallister syndrome was significantly older (p < 0.005) compared to maternal age for the general population, and similar to maternal age in cases of Down syndrome (p<0.5). Paternal age in cases of Pallister syndrome was that expected in the general population from the age of their spouses (p<0.9). These data complement the maternal age effect seen in other aneuploidy conditions and suggest, as is found in mosaic cases of Down syndrome, that the chromosomally normal cell line in Pallister syndrome arises post‐conception from a zygote already aneuploid consequent to meiotic nondisjunction.

Monosomy of chromosome No. 22 A case report

1. Krivit, W., and Good, R. A.: Simultaneous occurrence of mongolism and leukemia, Am. J. Dis. Child. 94: 289, 1957. 2. Miller, R. W.: Neoplasia and Downs syndrome, Ann. N. Y. Acad. Sci. 171: 637, 1970. 3. Holland, W. W., Doll, R., and Carter, C. O.: The mortality from leukemia and other cancers among patients with Downs syndrome (mongols) and among their parents, Br. J. Cancer 16: 177, 1962. 4. Foley, J. F., and Lemon, H. M.: Downs syndrome associated with an intracranial rhabdomyosarcoma and relative hypopituitarism, Nebr. State Med. J. 53: 384, 1968.

A controlled retrospective follow-up study of the impact of genetic counseling on parental reproduction following the birth of a Down syndrome child

Twenty‐three couples who had received genetic counseling after the birth of a Down Syndrome child (DSC) were closely match‐paired by race, religion, maternal age, paternal occupation, parental education and sex sibship order of the DSC with 23 non‐counseled couples who also had a DSC. When evaluated at least 11/2 years after the birth of the DSC or the genetic counseling, there were no significant differences between counseled and non‐counseled couples in knowledge of general genetics or recurrent risks for Down Syndrome, initiation of subsequent pregnancies, or utilization of prenatal diagnosis. Knowledge of general genetics and recurrent risks for Down Syndrome among our post‐counselees was poorer than that of two published immediate follow‐up reports. Although 18 of 46 couples initiated at least one more pregnancy after the birth of their DSC, only three couples (2 counseled; 1 non‐counseled) utilized prenatal diagnosis by amniocentesis.

X chromosome imprinting in fragile X syndrome.

SummaryLaird et al. (1987) hypothesized that there are at least four cis-acting alleles or ‘chromosome states’ at Xq27 that increasingly delay replication at this chromosomal area resulting in its increasing fragility in vitro. When on the inactive×chromosome, the proposed third (‘mutated’) allele can permanently block reactivation of its cis Xq27 area as the chromosome passes through female meiosis. Males and some females who inherit such an ‘imprinted’ fragile×chromosome (the fourth proposed allele) will be clinically affected due to impaired transcription of genes in the ‘imprinted’ Xq27 area. To test this hypothesis, late replication reverse banding patterns at Xq27 were evaluated in cultured lymphoblastoid cell lines from 25 subjects. Our data suggest that DNA replication of the presumed ‘imprinted’ Xq27 region in affected fragile×patients is indeed later relative to Xq27 on the active×chromosome in other subjects. These results support in part Lairds hypothesis of chromosomal imprinting in fragile×syndrome.