Robert S. Wilroy

X-autosome translocation in normal mother and effectively 21-monosomic daughter

A phenotypically normal mother carries a balanced X-21 translocation. Autoradiography of the mothers cells reveals that in all cells the normal X is late replicating. Her only pregnancy produced like-sex twins, one of whom is phenotypically and karyotypically normal. The co-twin is mentally retarded and has multiple anomalies. Her karyotype is 46,XX,der(21),t(X;21)(q11;p11?)mat. In the majority of informative cells from the daughter, one normal X and the entire X t replicate late. This maintains X dosage compensation, but results in effective monosomy 21. The phenotype of the infant is similar to others with 21q−.

Argininosuccinic aciduria: Investigation of an affected family

Two siblings with argininosuccinic aciduria were studied by an interdisciplinary team. Considerable variability in the clinical expression of this disorder was observed in comparison with previously reported cases. Detection of the heterozygous state in the parents and in a fetal sibling was demonstrated by tissue assay for argininosuccinase activity. Mental retardation and neurologic deficits in the affected children were irreversible with dietotherapy but growth was progressive and the general course was relatively benign.

Tissue limited mosaicism for unbalanced autosomal translocation in a child with congenital anomalies and mental retardation.

We studied a patient with a sporadic mental retardation/multiple congenital anomalies syndrome. Chromosome analysis showed a 46,XX, inv(9)(p11;q13) karyotype in all lymphocytes. Fibroblasts from two separate skin biopsies revealed a mosaic karyotype. Some 22.5% of fibroblasts had a karyotype like that of the lymphocytes, while 77.5% of fibroblasts had a karyotype 46,XX,inv(9)(p11;q13),der(12),t(12;?)(p13;?). The data in this case emphasize the drawbacks of confining cytogenetic analysis to lymphocytes.

FURTHER STUDIES OF THE TELECANTHUS-HYPOSPADIAS SYNDROME

The telecanthus-hypospadias syndrome is characterized by widely spaced inner ocular canthi and hypospadias, along with various combinations of other anomalies. We have had the opportunity to evaluate a total of 8 families, including 12 affected males. Three families contain multiple affected sibs. In one family, three brothers, including apparently identical twins, also have bilateral cleft lip and palate, and multiple other anomalies.In our series, the spectrum of associated anomalies includes mental retardation (8/12), cranial asymmetry (11/12), strabismus (7/12), cleft lip and palate (4/12), congenital heart disease (6/12), abnormalities of the urinary tract (4/12) and cryptorchidism (5/12). Mothers of affected males have demonstrated isolated telecanthus. The incidence of twinning seems to be increased in these families.This condition appears to be inherited as a dominant trait with no well documented instance of male-to-male transmission. It is in all likelihood more common than reflected in the literature. Among patients who are ascertained on the basis of either cleft lip with or without cleft palate, widely spaced ocular canthi, or apparently isolated hypospadias, the telecanthus-hypospadias syndrome constitutes a definable entity for the purposes of prognosis and genetic counseling.