Increased Sylvian fissure angle as early sonographic sign of malformation of cortical development.

OBJECTIVE: To evaluate Sylvian fissure development by assessing Sylvian fissure angles in fetuses with malformation of cortical development (MCD). METHODS: This was a retrospective study of 22 fetuses with MCD. Cases with a stored three-dimensional (3D) brain volume acquired at 18 + 0 to 30 + 6 weeks of gestation at an ultrasound-based research clinic between January 2010 and December 2017 were identified through a database. Of the 22 fetuses, seven had an extracranial abnormality, such as cardiac, renal, gastrointestinal and/or digital anomalies, and five had a minor abnormality such as micrognathia, low-set ears and/or single umbilical artery. To confirm the final clinical diagnosis of brain abnormality, postmortem histological findings or prenatal or postnatal magnetic resonance images were used. For measurement of Sylvian fissure angle, an anterior coronal plane of the fetal brain on transvaginal 3D volume multiplanar imaging was visualized as a single image from the three orthogonal views. The right and left Sylvian fissure angles were measured between a horizontal reference line (0°) and a line drawn along the upper side of the respective Sylvian fissure. The Sylvian fissure angle on both sides was plotted on the graphs of the reference ranges for gestational age in weeks. RESULTS: In 21 (95.5%; 95% CI, 86.8-100.0%) of 22 fetuses with MCD, the Sylvian fissure angle on one or both sides was larger than the 90th percentile of the normal reference. There was one case with apparent focal MCD in the parietal lobe, but the Sylvian fissure angles were normal. A case with apparent unilateral cortical dysplasia and one with apparent unilateral schizencephaly had conspicuous discrepancies between the left and right Sylvian fissure angles. Abnormal genetic test results were obtained in six cases, including four cases with a mutation in a single gene. CONCLUSIONS: This study has shown that the Sylvian fissures, as defined by the Sylvian fissure angle, have delayed development in most MCD cases prior to the diagnosis of the condition. The Sylvian fissure angle may potentially be a strong indicator for the subsequent development of cortical malformation, before the time point at which the gyri and sulci become obvious on the fetal brain surface. Further research is required to validate these findings. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Hereditary spherocytic anemia with deletion of the short arm of chromosome 8.

We describe a 30-month-old boy with multiple anomalies and mental retardation with hereditary spherocytic anemia. His karyotype was 46,XY,del(8)(p11.23p21.1). Genes for ankyrin and glutathione reductase (GSR) were localized to chromosome areas 8p11.2 and 8p21.1, respectively. Six patients with spherocytic anemia and interstitial deletion of 8p- have been reported. In these patients, severe mental retardation and multiple anomalies are common findings. This is a new contiguous gene syndrome. Lux et al. [1990: Nature 345:736-739] established that ankyrin deficiency and associated deficiencies of spectrin and protein 4.2 were responsible for spherocytosis in this syndrome. We reviewed the manifestations of this syndrome. Patients with spherocytic anemia and multiple congenital anomalies should be investigated by high-resolution chromosomal means to differentiate this syndrome.

Monoallelic expression of normal mRNA in the PIT1 mutation heterozygotes with normal phenotype and biallelic expression in the abnormal phenotype.

The combined deficiency of thyrotropin, growth hormone and prolactin, caused by PIT1 abnormality manifests in the homozygous or heterozygous state. We studied a patient having an allele with Arg271Trp mutation, which produces clinical symptoms in heterozygotes by a dominant-negative effect. However, in the family, her father, grandmother and aunts had the same mutation without clinical symptoms, although the proband had typical phenotypic expression. We analyzed the PIT1 transcript in peripheral lymphocytes by reverse transcription-polymerase chain reaction and found monoallelic expression of normal allele in the father and grandmother and skewed pattern of biallelic expression in the proband. The phenotypic expression of PIT1 abnormality may depend on different transcription of the PIT1 gene.

A Japanese patient with the Costello syndrome.

The Costello syndrome is characterized by dwarfism, unique cutaneous lesions, distinct facial gestalt, and mental retardation. We present a Japanese patient with the Costello syndrome. She showed high serum IgM level during the early infantile period. Nissen's fundplication was carried out to treat severe gastroesophageal reflux. Endocrinological investigations revealed a partial deficiency of growth hormone.

Localization of the spherocytosis gene to chromosome segment 8p11.22----8p21.

A case of hereditary spherocytosis (HS) is reported. Cytogenetic study revealed a de novo minute deletion of chromosome 8. The critical portion which affected the expression of the HS phenotype appeared to be localized to 8p11.22----8p21.1.

The oral manifestations of 4p- syndrome.

The oral manifestations of 80 reported cases of 4p- syndrome are analyzed and a new case is reported. Results indicate that the common pattern of cheilognathopharyngeal disorders in 4p- syndrome is an isolated cleft palate or a high-arched palate with micrognathia. Cases of cleft lip are only about 10% of the total. The significance of other reported aberrant phenomena cannot yet be estimated.

Loss of high frequency of sister chromatid exchanges in Epstein-Barr virus-established lymphoblastoid cell lines from two patients with Bloom's syndrome.

Seven lymphoblastoid cell lines were established through transformation by Epstein-Barr virus of peripheral blood lymphocytes from two patients with Bloom's syndrome (BS), the parents of a patient, and normal controls. High baseline levels of sister chromatid exchanges (SCEs) in peripheral blood lymphocytes of BS were reduced to about 10% of their initial value in BS lymphoblastoid cell lines, and the elevation of SCE frequencies induced by ethylmethanesulfonate was the same as in controls.

Male infant with cat cry syndrome and apparent absence of the Y chromosome.

We report a boy with cri-du-chat syndrome and apparent absence of the Y chromosome. The karyotype is interpreted as 45,X,del(5)(qter leads to p13:). The boy has normal male external genitalia and bilateral testes although no Y chromosome was found in lymphocytes or fibroblasts.

Reciprocal translocation t(5;6)(p13;q27) through three generations: case report of cri du chat syndrome.

A male infant with cri du chat syndrome was found to have a deletion of the short arm of No. 5 chromosome and which was due to maternal reciprocal translocation t(5;6)(p13;q27). His elder sister and his grandfather were also identified as the translocation carriers.

A case of neuraminidase deficiency associated with a partial beta-galactosidase defect. Clinical, biochemical and radiological studies.

Neuraminidase deficiency towards fetuin, 2 leads to 3 sialyllactose and 2 leads to 6 sialyllactose was found in cultured skin fibroblasts from a 10-year-old Japanese girl who exhibits craniofacial dysmorphism, a short neck, vertebral and pelvic deformities and macular cherry-red spots. Neuraminidase deficiency in this case seems the primary enzyme defect because the enzyme activity of her parents was intermediate. In addition, beta-galactosidase in leukocytes and cultured skin fibroblasts from the patient was found to be severely deficient, but could be detected in serum and urine. In the parents, beta-galactosidase activity was normal. There were moderately increased levels of urinary sialic acid-rich oligosaccharides and glycopeptides in the patient. The clinical and biochemical observations suggest that this case is very close to mucolipidosis I.

Hypersialyloligosacchariduria in mucolipidoses: a method for diagnosis.

A method is described for the detection of abnormal oligosaccharides in a small (5 ml) volume of urine, employing filtration on a Bio Gel P-6 column, determination of neutral sugar and bound sialic acid, and determination of creatinine content. With this method increased urinary excretion of sialic acid-rich oligosaccharides has been detected in nine patients with mucolipidoses (five cases of mucolipidosis II and four patients of mucolipidosis, with beta-galactosidase deficiency). The filtration patterns of oligosaccharides in mucolipidoses were clearly distinguishable from those in other inborn errors of metabolism. Total excreted oligosaccharides were increased 5--30-fold in these patients; mucolipidosis II, 640--1350 microgram neutral sugar/mg creatinine; control 54 +/- 20 microgram neutral sugar/mg creatinine. The oligosaccharides consisted of three sialic acid-rich fractions and were common in both types of mucolipidosis. Our data indicate that hypersialyoligosacchariduria is the main biochemical feature of both types of mucolipidosis.

Possible intrachromosomal duplication in a case of trisomy 9p.

A 5-year-old boy with multiple minor anomalies and mental retardation was found to have chromosomal condition of 46,XY,inv dup(9p) (pter leads to p13::p21 leads to p24::p13 leads to qter). The clinical features of the propositus fit well with those of trisomy 9p which have been established to be a clinical entity.

Nonrandom distribution of exchange points in patients with structural rearrangements.

High resolution studies of structural rearrangements were carried out using the G-band technique. A total of 220 breakage points were identified within individual bands from 117 unrelated cases born with a structural rearrangement. Breakage points were not evenly distributed along chromosomes in terms of G-band patterns. There was an excess involvement of light bands and a striking lack of dark bands in both reciprocal translocations and inversions. In reciprocal translocations, the middle part of a chromosome arm has less chance of being the site of an exchange than the terminal and centromeric parts. The implications of these results are briefly discussed.

A 6p trisomy detected in a family with a "giant satellite".

A very large (giant) satellite was observed on one of the D-group chromosomes of a malformed and mentally retarded infant and her father. Detailed cytogenetic studies revealed that the giant satellite represented, in fact, a der(15) chromosome of translocation t(6;15)(p21;p12 or 13). The proposita was trisomic for a part of 6p(6pter leads to 6p21). The father was a balanced carrier, however, the deletion of the short arm of a No. 6 was hard to detect in routine karyotype analysis.

Two cases of 8p trisomy in one sibship.

Two cases of 8p trisomy in one sibship are presented. The father was a balanced carrier of a translocation rcp (8;13) (p11; q34). Case 1 was a 2-year -old boy with multiple minor anomalies and severe mental retardation. Giemsa banding studies revealed that he was trisomic for the greater part of 8p (8p11 yields pter). When his mother became pregnant again, amniocentesis was carried out in the 17th week of gestation. The fetus (Case 2) was shown to have the same 8p trisomy as Case 1. The pregnancy was terminated in the 22nd week. An autopsy revealed no major anomalies. Clinical features of cases with 8 and 8p trisomy are reviewed briefly.