Mild Microcephaly Research Articles

Clinicopathological report of cerebroocular myopathy syndrome

PURPOSE: To report a case of cerebroocular myopathy syndrome with a focal absence of the Descemet membrane. DESIGN: Clinicopathological case report. METHODS: A clinical and histopathologic examination of eye, brain, and viscera of a white male newborn of normal term, who died at 11 days of age with the diagnosis of cerebroocular myopathy syndrome. RESULTS: The autopsy revealed hazy left cornea, hypoplasia of the cerebellum, and corpus collusum with mild microcephaly. Microscopy of the left eye showed the additional findings of a central focal defect of the Descemet membrane with an absence of the posterior third of central corneal stroma and delicate fibrous strands connected to the iris. CONCLUSION: The absence of the Descemet membrane and the missing posterior corneal keratocytes as well as the fibrous strands connecting the iris are findings to be added to the previously reported signs of cerebro-ocular myopathy.

Variegated aneuploidy in two siblings: Phenotype, genotype, CENP-E analysis, and literature review

Cytogenetic studies of 2 sisters with mild microcephaly, growth deficiency, and mild errors of morphogenesis demonstrated a unique combination of multiple trisomies, most often involving chromosomes 8 and 18 either together as sole trisomies or in combination with other chromosomes. Since neither sib has phenotypic anomalies associated with trisomy 8 or 18 mosaicism, the trisomies likely did not occur during embryogenesis, but later possibly due to a predisposition for mitotic instability. To determine if the observed chromosome instability may be related to centromere function, metaphase cells were characterized by immunofluorescence of the centromere protein, CENP-E. Hybridization of CENP-E antibodies, in combination with in situ hybridization of a chromosome 8 or 18 alpha-satellite probe, showed hybridization to chromosomes 8 and 18 in both normal and aneuploid cells from each patient. These data indicate that the chromosomes in each child contain functional and active centromeres. The clinical and cytogenetic findings in these 2 individuals are compared with 7 other previously reported individuals, each of whom have similar findings. Together, these studies support the notion that a recessive mitotic mutant may be responsible for the chromosomal mosaicism and for the resulting clinical phenotype.

Variegated aneuploidy in two siblings: Phenotype, genotype, CENP‐E analysis, and literature review

Cytogenetic studies of 2 sisters with mild microcephaly, growth deficiency, and mild errors of morphogenesis demonstrated a unique combination of multiple trisomies, most often involving chromosomes 8 and 18 either together as sole trisomies or in combination with other chromosomes. Since neither sib has phenotypic anomalies associated with trisomy 8 or 18 mosaicism, the trisomies likely did not occur during embryogenesis, but later possibly due to a predisposition for mitotic instability. To determine if the observed chromosome instability may be related to centromere function, metaphase cells were characterized by immunofluorescence of the centromere protein, CENP-E. Hybridization of CENP-E antibodies, in combination with in situ hybridization of a chromosome 8 or 18 α-satellite probe, showed hybridization to chromosomes 8 and 18 in both normal and aneuploid cells from each patient. These data indicate that the chromosomes in each child contain functional and active centromeres. The clinical and cytogenetic findings in these 2 individuals are compared with 7 other previously reported individuals, each of whom have similar findings. Together, these studies support the notion that a recessive mitotic mutant may be responsible for the chromosomal mosaicism and for the resulting clinical phenotype. Am. J. Med. Genet. 75:45–51, 1998. © 1998 Wiley-Liss, Inc.

Identification of an unbalanced cryptic translocation t(9;17)(q34.3;p13.3) in a child with dysmorphic features

We report a case of an unbalanced cryptic telomeric translocation 46,XY,der(17),t(9;17)(q34.3;p13.3) in a boy with dysmorphic features and developmental delay. The proband had intrauterine growth retardation, postnatal short stature, and mild microcephaly. Magnetic resonance imaging showed incomplete myelination, but no evidence of lissencephaly. Cytogenetic analysis of the proband's peripheral blood showed an abnormal 17p. Fluorescence in situ hybridisation (FISH) with a Miller-Dieker cosmid probe did not detect a deletion for that area. Further analysis with a 17p telomere specific probe identified an unbalanced telomeric translocation. The same probe was used to determine the presence of an apparent balanced translocation t(9;17)(q34.3;p13.3) in the mother of the proband. The balanced translocation was confirmed with two cosmids that map distally on 9q34.3. Two phenotypically normal half sibs, a maternal aunt, a maternal uncle, and the maternal grandmother were found to be balanced translocation carriers as well. A subtle translocation carriers as well. A subtle translocation is one mechanism that can produce an abnormal phenotype in a patient who had a normal karyotype at lower band resolution levels.

Phenotype of 49,XXYYY

A 7-year-old boy with 49,XXYYY karyotype is reported. Physical examination revealed facial dysmorphism, mild microcephaly, limitation of supination at the elbows, delayed bone age and moderate mental retardation.

Anesthetic considerations of an infant with Beckwith-Wiedemann syndrome

The case of a 3-day-old infant with Beckwith-Wiedemann syndrome who required anesthetic care during closure of an abdominal wall defect is presented. Beckwith-Wiedemann syndrome comprises a constellation of clinical features, including macroglossia, macrosomia, omphalocele, visceromegaly, mild microcephaly, facial nevus flammeus, horizontal earlobe creases, and renal medullary dysplasia. Due to the high rate of omphalocele in this syndrome, anesthetic care is frequently required during the neonatal period. Many of these infants (greater than 50%) are born prematurely. Therefore, their anesthetic care may be further complicated by associated diseases of prematurity, such as hyaline membrane disease. Additional anesthetic implications of this syndrome relate to the occurrence and management of hypoglycemia and polycythemia. Careful intraoperative management of glucose homeostasis is particularly important, since eventual neurologic outcome and intelligence will be normal provided prolonged neonatal hypoglycemia is avoided. Preoperative evaluation of the cardiac and genitourinary system, including echocardiography and renal ultrasound, are recommended because of the frequent occurrence of associated anomalies with omphalocele.

D(+)-Glyceric Aciduria: Etiology and Clinical Consequences

A family comprising mother, father, and five children is described. Four of the children were found to excrete massive amounts of D(+)-glyceric acid in their urine. This was verified by gas chromatography-mass spectrometry and the configuration determined by capillary gas chromatography of O-acetylated menthyl esters. The excretion ranged from 10.8 to 19.9 mmol/24 h. The remaining child and the parents showed no evidence of this unusual metabolite. The virtual absence of clinical manifestations in this family was particularly interesting. Only two of the children showed any clinical abnormality and this was limited to mild microcephaly and speech delay; the other two children found to excrete large amounts of D(+)-glycerate were healthy and developmentally normal at 7 y and 9 y of age. There was a marked increase in the excretion rate of D(+)-glycerate in response to both oral fructose and serine loading. These results are consistent with a deficiency of D(+)-glycerate kinase and indicate the potentially benign nature of this disorder.

Interstitial Deletion of the Long Arm of Chromosome 13 and Retinoblastoma

AbstractA female infant is reported in whom bilateral retinoblastoma developed due to interstitial delection of the long arm of chromosome 13. Her chromosome karyotype examined with peripheral lymphocytes proved to be 46, XX, del (13) (q12.3 q21.2). Parental chromosome karyotypes were normal.Clinical symptoms were bilateral retinoblastoma, retardation of growth and development, and mild microcephaly. No other marked dysmorphic features were noted.

Association of Hirschsprung Disease and Bilateral Preaxial Polydactyly

AbstractTwo cases with association of Hirschsprung disease and preaxial polydactyly occurring in siblings were reported.The proband was a female infant examined on the 12th day after birth. Major findings were as follows: growth retardation, mild microcephaly, rightanophthalmia, left exophthalmus associated with double disk and coloboma choroidae, ocular hypotelorism, cleft lip and palate, and bilateral preaxial polydactyly. CT scan of the brain revealed agenesis of the corpus callosum and atrophy of the cerebral cortex.Autopsy revealed alobar holoprosencephaly and agenesis of the corpus callosum, right optic nerve and olfactory nerve. Aganglionosis of the rectumwas noted at a site 10 cm from the anus.When her brother was born, bilateral preaxial polydactyly was found. He had Hirschsprung disease as well.

Abnormal regulation of circulating 25-hydroxyvitamin D in the Williams syndrome.

THE Williams syndrome is characterized by the triad supravalvular aortic stenosis, mental retardation, and an elfin facies.1 , 2 In addition, mild microcephaly, neurologic dysfunction, hallux valgus, hernias, pectus excavatum, and other congenital cardiac and vascular defects may be present. The unique facies is characterized by a medial eyebrow flare, short palpebral fissures, ocular hypotelorism, a depressed nasal bridge, periorbital fullness, strabismus, blue eyes, a stellate pattern in the iris, prominent lips, and molar hyperplasia.2 The syndrome is often associated with idiopathic hypercalcemia of infancy, which usually occurs in the first year of life.3 4 5 6 7 8 9 10 11 Patients have increased sensitivity to vitamin D.5 , 6 Balance . . .

A case of the orocraniodigital (Juberg-Hayward) syndrome.

A female with the orocraniodigital (Juberg-Hayward) syndrome is described in whom, in addition to bilateral cleft lip and palate, mild microcephaly, and anomalous thumbs and toes, there was absence of...

The Williams elfin facies syndrome: A new perspective

Evaluation of 19 patients with the Williams elfin facies syndrome, in order to more completely delineate the total spectrum of the disorder, indicates that "infantile hypercalcemia, peculiar facies, supravalvular aortic stenosis" designation which was heretofore used is inappropriate. Only 32% of the patients have evidence of supravalvular aortic stenosis and not one of them has had documented hypercalcemia, including eight patients who had a serum calcium determination in the first year of life. Rather, the most consistent features are growth deficiency which is predominantly of postnatal onset, mild microcephaly with mental deficiency, and an altered pattern of facial development which includes short palpebral fissures, a stellate pattern in the iris, medial eyebrow flare, a depressed nasal bridge with anteverted nares, and thick lips. The disorder is a sporadic occurrence of unknown etiology.

Probable localization of a triosephosphate isomerase gene to the short arm of the number 5 human chromosome.

IN our human gene localization studies we have sought abnormal inheritance patterns of qualitative gene markers and have evaluated possible gene dose effects through quantitative enzyme assays in patients with abnormal chromosome constitutions. During these studies a patient with the cat cry syndrome was found to have a half normal value for red blood cell triosephosphate isomerase (EC 5.3.1.1). Clinical features which suggest that the patient has the cat cry syndrome include mental and physical retardation, a weak plaintive cry, moon facies, mild microcephaly, epicanthal folds, antimongoloid slant to the palpebral fissures and hypertelorism1.

26 Deletion of Chromosome No. 18 (Long Arm). A New Syndrome

Four unrelated examples of partial deletion of the long arm of chromosome No. 18 have been briefly reported by us (Lancet ii: 641 [1966]). These patients have now been studied in detail.The typical features of this syndrome are mental retardation, short stature, impaired hearing with atretic or narrow ear canals, prominent antihelix, mild microcephaly, typical facies manifested by prominent forehead—perioral areas and deep set eyes, proximal implantation of the thumbs, increased number of whorl fingerprint patterns, hypotonia, vertical tali, fundoscopic anomalies and asymptomatic congenital heart anomalies.Relatives of three of the patients had normal chromosomes. The father and two siblings of the fourth patient had one metacentric No. 18, interpreted as a pericentric inversion. The deletion in this last patient probably arose by a crossover in the father between the metacentric and the normal No. 18 (‘aneusomy by recombination’).These four patients represent partial monosomy No. 18 but nonetheless the findings are not obviously the antithesis of the trisomy 18 syndrome.The retardation and morbidity associated with this chromosome disorder are less severe than those found with the usual autosomal trisomies. Since survival does not seem to be affected by this disorder, these patients will likely be found among older children. (SPR)

Le Pied-Bot

To the Editor:— The picture on the cover of the Feb 28 issue ofThe JournalLe Pied-Bot interests me, as one who has specialized in cerebral palsy. I have long contended that this child did not represent a classical clubfoot, but illustrated more a right hemiplegia, in which the internal rotators and flexors were more spastic than the external rotators and extensors. Although I use the word spastic, this could be a tension athetoid hemiplegia. The factors favoring the hemiplegia include the facial asymmetry and the tooth markings so frequently seen in the patient with congenital cerebral palsy. Although the child's expression is one of cheerfulness, it is not necessarily one of intelligence. There is a possibility of a mild microcephaly; certainly the frontal lobes are not large. The most compelling feature of all is the fashion in which he carries his right upper extremity, internally rotated, dropped at