Frank Greenberg

The association of the DiGeorge anomalad with partial monosomy of chromosome 22

We have seen three unrelated patients with the DiGeorge anomalad who also had the same deletion of chromosome 22 (pter leads to qll). In each, the remaining long arm material (qll leads to qter) was translocated to a different autosome. Our patients and a review of the literature, including a recent report of a family having four infants with the DiGeorge anomalad and the same deletion of chromosome 22 (de la Chapelle et al: Hum Genet 57:253, 1981), make a strong argument for at least some cases of the DiGeorge anomalad arising from a deletion of the pericentromeric region of chromosome 22.

Miller-Dieker syndrome: Lissencephaly andmonosomy 17p

Miller-Dieker syndrome, which includes lissencephaly and a characteristic phenotypic appearance, has been reported to have an autosomal recessive pattern of inheritance. However, we have found abnormalities of chromosome 17 in two of three unrelated patients with this syndrome, one with a ring chromosome 17 and the other with an unbalanced translocation resulting in partial monosomy of 17p13. A review of the literature revealed five additional patients in three families, who had Miller-Dieker syndrome and an abnormality of 17p. Thus, we propose that monosomy of distal 17p may be the cause of Miller-Dieker syndrome in some patients.

Original articleMiller-Dieker syndrome: Lissencephaly andmonosomy 17p1

Miller-Dieker syndrome, which includes lissencephaly and a characteristic phenotypic appearance, has been reported to have an autosomal recessive pattern of inheritance. However, we have found abnormalities of chromosome 17 in two of three unrelated patients with this syndrome, one with a ring chromosome 17 and the other with an unbalanced translocation resulting in partial monosomy of 17p13. A review of the literature revealed five additional patients in three families, who had Miller-Dieker syndrome and an abnormality of 17p. Thus, we propose that monosomy of distal 17p may be the cause of Miller-Dieker syndrome in some patients.

Ophthalmic Manifestations of Smith-Magenis Syndrome

PURPOSEnThe Smith-Magenis syndrome (SMS) is a multiple-anomaly, mental retardation syndrome associated with deletions of a contiguous region of chromosome 17p11.2. Prior reports have described ophthalmic anomalies with SMS, including telecanthus, ptosis, strabismus, myopia, iris anomalies, cataracts, optic nerve hypoplasia, and retinal detachment. This report defines the ophthalmic spectrum in 28 individuals with SMS subjected to a multidisciplinary clinical and molecular survey.nnnMETHODSnIndividuals with deletion of chromosome 17p11.2 detected by high-resolution cytogenetic analysis underwent complete ophthalmologic evaluation comprised of ophthalmic history, visual acuity, cycloplegic refraction, motility, and biomicroscopic and ophthalmoscopic examination.nnnRESULTSnAmong the 28 subjects, ranging in age from 0.8 to 29.3 years, the most frequent ocular findings were iris anomalies (68%), microcornea (50%), myopia (42%), and strabismus (32%). Bilateral microphthalmos with uveal and retinal coloboma was observed in one individual. No subject had cataract or retinal detachment.nnnCONCLUSIONSnThis is the largest single-center series of subjects with SMS that includes ophthalmic evaluation. As in prior reports, iris anomalies and strabismus were observed, but microcornea had not been noted previously. The absolute refractive error was hypermetropic in half of these subjects. Cataract, ptosis, and retinal pathology, including detachment, were not observed in any subject. All individuals with SMS should be evaluated by an ophthalmologist, with special attention to strabismus, microcornea, iris anomalies, and refractive errors.

Maternal serum α-fetoprotein, β-human chorionic gonadotropin, and unconjugated estriol levels in midtrimester trisomy 18 pregnancies

Objective : The purpose was to evaluate the levels of maternal serum human chorionic gonadotropin, α-fetoprotein, and unconjugated estriol in trisomy 18 pregnancies compared with normal singleton pregnancies. Study design : Sera from 14 trisomy 18 pregnancies (13 retrospectively and one prospectively ascertained) were analyzed for human chorionic gonadotropin, α-fetoprotein, and unconjugated estriol. Results : The α-fetoprotein levels in the 10 trisomy 18 pregnancies without open neural tube or ventral wall defect had a median of 0.65 multiple of the median, although two had α-fetoprotein levels above 2.5 multiples of the median. The human chorionic gonadotropin levels had a median of 0.32 multiple of the median and the unconjugated estriol levels had a median of 0.56 multiple of the median. Although most women with trisomy 18 pregnancies had serum human chorionic gonadotropin levels that were 5.0 multiples of the median). Conclusion : Our data are partially consistent with those previously published but suggest the possibility of a bimodal distribution of α-fetoprotein and human chorionic gonadotropin levels in trisomy 18-affected pregnancies, unrelated to a neural tube or abdominal wall defect. The efficiency of screening for trisomy 18 prospectively, using the three serum markers, requires further evaluation.

Congenital deficiency of α-fetoprotein

Although α-fetoprotein may play a role in fetal immune function or in maintenance of osmotic pressure, its exact function is unknown. We report two infants documented to have congenital deficiency of α-fetoprotein. One infant had cord blood levels

Dysmorphic features in patients with complex glycerol kinase deficiency

Complex glycerol kinase deficiency is a contiguous gene syndrome consisting of a deletion of the glycerol kinase locus, together with the genes for adrenal hypoplasia congenita or Duchenne muscular dystrophy or both. We describe an infant with complex glycerol kinase deficiency and mildly dysmorphic features similar to those seen in other patients, including an hourglass appearance of the middle of the face; hypertelorism; rounded palpebral fissures; esotropia; wide, flattened earlobes; and a downturned mouth. The combination of medical history and characteristic facies should prompt the request for specific laboratory tests diagnostic for this potentially treatable condition.

The effect of gestational age on the detection rate of Down's syndrome by maternal serum α-fetoprotein screening

Low levels of maternal serum alpha-fetoprotein are currently being used to screen for Downs syndrome in midpregnancy. Because of the possibility that gestational age may affect the detection rate of Downs syndrome, we analyzed maternal serum AFP levels and gestational age in 51 Downs syndrome pregnancies that had been confirmed by amniocentesis or at birth, and we compared these pregnancies with 3239 screened singleton pregnancies with known normal outcomes. The highest yield of a low risk for Downs syndrome associated with maternal serum alpha-fetoprotein occurred at 16.5 to 17.5 weeks gestation. Our data suggest that maternal serum alpha-fetoprotein screening for Downs syndrome should be done between 16 and 18 weeks gestation, which is the gestational age currently recommended for neural tube defect screening.

AN OPHTHALMOLOGICAL STUDY OF PATIENTS WITH WILLIAMS SYNDROME

Between July, 1982 and December 1986, 36 patients with Williams syndrome were evaluated. The mean age at examination was 8.2 years with a range of 0.5-43 years. There were 30 whites, 2 blacks, 2 Hispanics, and 1 Asian. There was a tendency toward ocular hypotelorism with short palpebral fissures; the mean inner canthal distance was 38% for age, while the outer canthal distance was 27%. Of the white patients, 23 had blue irides, 6 hazel and 1 brown. All 6 non-white pateitns had brown irides. All patients with brown irides and, in addition, six patients with blue and three patients with hazel irides did not have stellate iris patterns. Thirty-one percent of the patients had strabismus, similar to previous observations. Three types of optic disc and vascular changes not previously described in the syndrome were noted. Hypermetropic discs were noted in 13 patients. Seventeen patients had simplex vertical branching and three had situs inversus vasorum. Although the latter two findings are considered normal variants, they seem more common in Williams syndrome patients. Accentuated retinal vascular tortuosity has been previously reported, but was not present in any of our patients. In addition, no patients had evidence of ocular manifestations of hypercalcemia. Because of the high Incidence of ocular manifestations in Williams syndrome, we recommend ophthalmologic evaluation of all such patients.

PROSPECTIVE MSAFP SCREENING FOR DOWN SYNDROME: THE BAYLOR EXPERIENCE

After the initial reports of the association of fetal trisomy 21 with low maternal serum alpha fetoprotein (MSAFP) levels in retrospective studies in 1984, we began using low MSAFP levels as a means of screening for an increased risk of Down syndrome using reagents from Clinical Assays. In 1985, a total of 4929 women were screened, of whom 312 (6.3%) had an initial low MSAFP levels. Of these women, 217 (70%) had levels below the level of reliability of the assay and all but 33 had normal levels on repeat 1-2 weeks later. None of these women had a fetus or infant with trisomy 21 by amniocentesis or at birth. Ninety-five women (1.9%) had levels below half the median. Of these women, 12 had persistently low levels on repeat. A total of 21 amniocenteses were done in this group. Three fetuses with trisomy 21 and one fetus with trisomy 18 were detected, a rate of 7.1% fetal trisomy among those women who had amniocentesis for low MSAFP levels. No cases of trisomy 21 were missed. Thus far in 1986, over 10,000 women have been screened. The rate of fetal trisomy in amniotic fluid is about 3%. One infant with trisomy 21 is known to have been missed.