Richard C. Juberg

Partial monosomy 7q syndrome due to distal interstitial deletion

SummaryA female infant was ascertained at 10 weeks because of failure to thrive and a peculiar cry and was found to have few morphologic variants. Her karyotype was 46,XX,del(7)(q3105: :q3405). The parental karyotypes were normal. At one year she manifested physical retardation and development delay and required surgery for gastroesophageal incompetence. The phenotypic characteristics of this patient and those of six previously reported cases of 7q medial or distal interstitial deletion include many anomalies. Morphologic abnormalities of the head, ears, eyes, mouth, chest, hands, feet, and nerves combined with characteristics of birth weight, growth, and development define a detectable syndrome. An unusual cry may help in the recognition of this new syndrome.

Dissociation of a t(12;21) resulting in a normal cell line in two trisomic 21 sons of a nonmosaic t(12;21) father?

SummaryA normal cell line arising from a translocation, t(12;21), possibly by dissociation, was observed in two brothers in early life. Each was conceived as trisomic 21 by their 45,XY,-12,-21,+t(12;21) father, who was phenotypically normal. Each brother showed morphologic manifestations of trisomy 21 syndrome, and each was mildly mentally retarded. Dermatoglyphic indices were not diagnostic of trisomy 21 syndrome. At 4 months the younger brother had a 50:50 proportion of trisomic:normal blood cells which became 25:75 of trisomic 21:normal at 36 months. The older brother had a 25:75 proportion of trisomic 21:normal when first studied at 41/2 years. A similar t(12;21) has not previously been reported. The occurrence of an apparently normal cell line arising spontaneously is unique.

Prenatal Sonographic Renal Findings Associated with Trisomy 13

Prenatal ultrasonographic renal findings are described in three cases of trisomy 13. The association of renal anomalies, including hyperlobulation, dysplasia and presence of cortical cysts, with trisomy 13 has been reported previously. This series, however, points out the importance of considering trisomy 13 as a possible diagnosis and recommends prenatal diagnosis when renal abnormalities are found on ultrasound examination.

114: FAMILIAL SEX CHROMOSOMAL MOSAICISM

Familial mosaicism has rarely been reported. Its recognition poses problems in prognosis, especially prenatally.A 36-year-old white woman, gravida 1, following Clomid stimulation had an amniocentesis at 19 weeks. Of 65 spreads, 82% were 45,X and 18% 46,XX. A second amniocentesis 3 weeks later showed 73% 45,X and 27% 46,XX in 37 spreads. Thorough genetic counseling with discussion of the Turner mosaic phenotype preceded a dedision to continue the pregnancy. At term the female infant had normal mensurations, no stigmata of the 45,X syndrome, and blood study showed 38% 45,X, 60% 46,XX and 2% 47,XXX in 40 spreads.The phenotypically normal mother had blood studies 2 months apart: (1) N = 41 with 10% 45,X, 83% 46,XX, and 7% 47,XXX; (2) N = 100 with 5% 45,X, 94% 46,XX, and 1% 48,XXXX. The phenotypically normal maternal grandmother, 74, showed 5% 45,X, 90% 46,XX, and 5% 47,XXX in 80 spreads, and the phenotypically normal maternal uncle, 39, showed 2.5% 45,Y, and 97.5% 46,XY in 40 spreads.Thus, 3 generations of females showed sex chromosomal mosaicism. The possibility of familial mosaicism reaches critical importance in interpreting prenatal mosaicism.

764 LEUKOCYTE CHROMOSOMES FROM PARENTS OF CYTOGENETICALLY ABNORMAL OFFSPRING

Hypermodal spreads are less frequent than hypomodals in routine chromosomal preparations. Hypomodals are probably artifacts resulting from preparative technique. However, hypermodals may signify mosaicism or a tendency to misdivision.Our materials were 435 leukocyte cultures of cells from phenotypically abnormal or normal subjects studied during 38 months in a diagnostic laboratory. Most preparations were G-banded, and 2 or more observers analyzed deviations from modality.There were no apparent temporal or sequential patterns to appearance among 14,710 spreads of 27 hypermodals (frequency = 1/545): 9 spreads with a single additional autosome; 2 with +7, 2 with isochromosome 11q, 2 with a fragment, 3 with +21, 3 with +Y, and 4 with +X; and 2 spreads each with 2 extra chromosomes.The frequency of hypermodals was 1/156 among 30 parents of 16 aneuploid offspring: 10 with +21, 2 with +18, 1 with +13, 1 with XXY, 1 with XXX, and 1 with XXXXY. Comparisons showed: (1) a frequency of 1/681 among the remaining 405 subjects (P<0.001 by X12); (2) a frequency of 1/810 among 50 similarly aged parents (0.02>P>0.01 by X12). Moreover, the addition of an X or Y occurred in 0.86 of the hypermodals among the parents of aneuploid progeny in contrast to the remaining group, in which the frequency of X or Y hypermodality was 0.05.These parents of aneuploids showing significant mitotic misdivision in vitro, may tend to meiotic nondisjunction in vivo.

but the family history was negative

At least eight possible explanations make the diagnosis of a genetically determined disorder compatiblewith a negative family history. In the interests of the patient, the family and a clearer understanding of genetic clinical disorders it behooves all to respect these possiblities.