Re: True agonadism: Report of a case analyzed with Y‐specific DNA probes

Abstract

We read with interest the report of Maciel-Guerra et al. (1991) of a 5-year-old child with a 46,XY karyotype, severe psychomotor and physical retardation, and female external genitalia. Recently we saw a similar case.Our patient was the only child of healthy unrelated parents born after an uncomplicated pregnancy; birth weight was 3,178 g, and birth length 50.8 cm. The father was 24 and the mother 27 years old. She was first evaluated at age 4 months when she presented with global developmental delay, microcephaly, and nystagmus. A CAT scan of the brain showed absence of the cerebellum, pachygyria, absence of the corpus callosum, and ventricular dilatation.The family history was non-contributory. The mother has four sisters and no brothers. All of her sisters had normal menarche; two have had healthy children.On physical examination the infant was between the 10th and 25th centiles for length, at the 25th centile for weight, and well below the 3rd centile for head circumference. She was hypotonic with mild plagiocephaly. She had intermittent nystagmus; her ears were low-set with normal configuration. She had a "carp-shaped" mouth with marked micrognathia. There were no cardiac murmurs and no abdominal organomegaly. She had female external genitalia.Blood for karyotyping was obtained. When the results of 46,XY were reported, we considered the possibility that there had been a mix-up of samples in the laboratory and repeated the study. Again, the results showed 46,xY; a total of 32 metaphases was examined. A prometaphase study at the 700 band level did not show deletion of the number 17 chromosomes. The Y chromosome appeared normal by Q banding.When seen in follow-up at age 7 months, global developmental delays persisted. She did not have clinically recognized seizures and continued to feed and grow well, although she was still profoundly hypotonic.A pelvic ultrasound examination showed no evidence of a uterus and no identifiable gonads.

XX-agonadism in a fetus with multiple dysraphic lesions: A new syndrome

“…The fact that we have had two familial observations and one isolated case suggests that cases are being overlooked or not reported. The malformation pattern of the present case is again unique and presents a newly recognized syndrome clearly distinct from other reports [Sarto and Opitz, 1973;Carey et al, 1978;Opitz and Gilbert, 1982;Carmi et al, 1990;Ma-ciel-Guerra et al, 1991;Meacham et al, 1991;Kushnik et al, 1992;Maaswinkel-Mooij and Stokvis-Brantsma, 1992;Kennerknecht et al, 1993Kennerknecht et al, , 1995Sybert et al, 1995].…”

A Gender Assessment Team: experience with 250 patients over a period of 25 years

“…Although the focus of the Team has been on infants and children with disorders restricted to the genitalia, 27 patients with 22 different multisystem genetic syndromes were discussed (Table 1), including three infants with cloacal exstrophy and three with panhypopituitarism. One infant had X-linked lissencephaly and agenesis of the corpus callosum with ambiguous genitalia (XLAG), 31 a disorder caused by mutations in the ARX gene. 32 Overall, we failed to establish a diagnosis for 29 individuals, representing 12% of the cohort.…”

“…The knowledge of this association provides reassurance that male sex assignment is appropriate and routine management of hy- Our group has also identified at least two new syndromes: (1) three males (including two brothers) with micropenis without hypospadias, testicular regression with poor response to HCG stimulation, and microcephaly 40 and (2) a phenotypic female with XLAG syndrome (X-linked lissencephaly with ambiguous genitalia) and 46,XY karyotype, one of the first to be described. 31,32 Evolution of the approach Certain themes have emerged as the Team reviewed its experience and tried to respond to the recommendations of the consensus statement. 5,6 The sophistication of cytogenetic, molecular, and endocrinologic testing options has increased over the past two decades.…”