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Background: Acute upper limb ischemia (AULI) is a potential complication associated with massages of occluded vascular accesses in patients undergoing hemodialysis. Pharmacological thrombolysis, endovascular intervention and surgical intervention are possible treatment options. Deciding the appropriate treatment strategy is still a controversial issue. Case Presentation: The patient was a 43-year-old woman with renal failure who underwent hemodialysis and peritoneal dialysis. She was found to have an arteriovenous graft (AVG) thrombosis at the start of a hemodialysis session. She underwent massage of the vascular access, and immediately after the massage, she reported pain and cyanosis in her right-hand fingers and was referred to our hospital. Duplex ultrasonography revealed a large number of thrombi in the brachial, radial and ulnar arteries. AULI due to brachial artery thrombosis was diagnosed and surgical intervention was performed on the same day. The vascular wall of the forearm artery was incised vertically against the running vessel and thrombi around the bifurcation of the radial and ulnar arteries were removed. Angiography guided-surgical intervention was performed and improvement in blood flow was achieved. The patient was discharged on the second day after the operation. Conclusion: Surgical intervention has been reported as an effective treatment of AULI due to brachial artery thrombosis after massage of an occluded vascular access.

Kabuki syndrome is characterized by a variable degree of intellectual disability, characteristic facial features, and complications in various organs. Many variants have been identified in two causative genes, that is, lysine methyltransferase 2D (KMT2D) and lysine demethylase 6A (KDM6A). In this study, we present the results of genetic screening of 100 patients with a suspected diagnosis of Kabuki syndrome in our center from July 2010 to June 2018. We identified 76 variants (43 novel) in KMT2D and 4 variants (3 novel) in KDM6A as pathogenic or likely pathogenic. Rare variants included a deep splicing variant (c.14000-8C>G) confirmed by RNA sequencing and an 18% mosaicism level for a KMT2D mutation. We also characterized a case with a blended phenotype consisting of Kabuki syndrome, osteogenesis imperfecta, and 16p13.11 microdeletion. We summarized the clinical phenotypes of 44 patients including a patient who developed cervical cancer of unknown origin at 16 years of age. This study presents important details of patients with Kabuki syndrome including rare clinical cases and expands our genetic understanding of this syndrome, which will help clinicians and researchers better manage and understand patients with Kabuki syndrome they may encounter.

Amyloidosis is known as a group of diseases that causes various disorders because of deposition of amyloid protein in various organs. Amyloidosis occurring in the retroperitoneum is a rare disease. We report a 75-year-old male patient presented to our hospital because he was identified with a retroperitoneal mass incidentally by CT. Laparoscopic surgery was performed to resect the tumor. In the histopathological specimen, amyloid was found in the fibrous soft tissue by Congo red staining. This is the first report to document a primary solitary amyloidosis of the retroperitoneum without systemic amyloidosis, which was resected using the laparoscopic approach.

We report a 34-year-old Japanese female with the vascular type of Ehlers-Danlos syndrome. She had thin translucent skin, extensive bruising, toe joint hypermobility, left lower extremity varicose veins, and chronic wrist, knee and ankle joint pain. She also had dizziness caused by autonomic dysfunction. Magnetic resonance angiography showed tortuous vertebral and basilar arteries, mild left carotid canal bulging, and right anterior tibial artery hypoplasia. Electron microscopic examinations of a skin biopsy revealed extremely dilated rough endoplasmic reticulum in dermal fibroblasts and wide variability of individual collagen fibril diameters. A molecular analysis using a conventional total RNA method and a high-resolution melting curve analysis using genomic DNA revealed a novel missense mutation within exon 48 of the COL3A1 gene, c.3428G>A, leading to p.Gly1143Glu.

Costello syndrome (CS) is a congenital disease that is characterized by a distinctive facial appearance, failure to thrive, mental retardation and cardiomyopathy. In 2005, we discovered that heterozygous germline mutations in HRAS caused CS. Several studies have shown that CS-associated HRAS mutations are clustered in codons 12 and 13, and mutations in other codons have also been identified. However, a comprehensive comparison of the substitutions identified in patients with CS has not been conducted. In the current study, we identified four mutations (p.G12S, p.G12A, p.G12C and p.G12D) in 21 patients and analyzed the associated clinical manifestations of CS in these individuals. To examine functional differences among the identified mutations, we characterized a total of nine HRAS mutants, including seven distinct substitutions in codons 12 and 13, p.K117R and p.A146T. The p.A146T mutant demonstrated the weakest Raf-binding activity, and the p.K117R and p.A146T mutants had weaker effects on downstream c-Jun N-terminal kinase signaling than did codon 12 or 13 mutants. We demonstrated that these mutant HRAS proteins induced senescence when overexpressed in human fibroblasts. Oncogene-induced senescence is a cellular reaction that controls cell proliferation in response to oncogenic mutation and it has been considered one of the tumor suppression mechanisms in vivo. Our findings suggest that the HRAS mutations identified in CS are sufficient to cause oncogene-induced senescence and that cellular senescence might therefore contribute to the pathogenesis of CS.

Aim: It has been well described that large residual urine volumes (≥300 mL) affect renal function in advanced benign prostatic hyperplasia (BPH). However, it is not clear whether small residual urine volumes (

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.

Pallister-Killian syndrome (PKS) is a disorder caused by a mosaic tetrasomy of chromosome 12p, which manifests with dysmorphism, intellectual disabilities, auditory disturbance, and epilepsy. Here, we describe the findings of brain magnetic resonance (MR) imaging in two patients with PKS. One patient, a 43-year-old man, showed multiple lesions with high signal intensity on T2-weighted image (WI) in the basal ganglia, and widespread T2 elongation in the periventricular white matter. The same signal change was also present in the pontine base. The other patient, a 37-year-old woman, showed T2-high lesions in the bilateral putamina and the parietal periventricular white matter. There was prominent atrophy of the cerebellum and brainstem in this latter case. Both cases showed cortical atrophy with frontal predominance, with accompanying dilatation of the lateral ventricles. Hypoplastic corpus callosum was also present in both cases. Cerebral atrophy with ventricular dilatation has been often described in PKS cases, but many of the MR findings in the present patients have never been reported. Such findings may appear with advancing age in PKS. Since 12p mosaicism is rarely detected in peripheral blood lymphocytes, examination of buccal mucosal cells with fluorescent in situ hybridization method is preferable for the diagnosis of PKS. Recognition of the characteristic features on cranial MR imaging, in addition to the characteristic facial appearance in adulthood, should prompt the correct diagnosis of adult PKS patients.

The 1p36 deletion syndrome is a newly delineated multiple congenital anomalies/mental retardation syndrome characterized by mental retardation, growth delay, epilepsy, congenital heart defects, characteristic facial appearance, and precocious puberty. We analyzed 11 patients by fluorescence in situ hybridization (FISH) using commercially available bacterial artificial chromosome and P1-derived artificial chromosome genomic clones to define the chromosomal deletion responsible for the 1p36 deletion syndrome. Cytogenetic investigation revealed two cases with a terminal deletion of 1p36. Nine patients had an apparently normal karyotype with standard G-bands by trypsin using Giemsa (GTG), but FISH screening with the highly polymorphic genetic marker D1Z2, which is mapped to 1p36.3 and contains an unusual reiterated 40-bp variable number tandem repeat, revealed a submicroscopic deletion. All patients had severe to profound mental retardation. Based on the University of California Santa Cruz Genome Browser, we constructed a deletion map and analyzed the relationship between neurological findings and chromosomal deletions for the 11 cases. Six cases had intractable epilepsy and three had no seizures. The common deletion interval was about 1 million base pairs (Mbp) located between RP11-82D16 and RP4-785P20 (Rho guanine exchange factor (GEF) 16). The severity of clinical symptoms correlates with the size of the deletion. This is demonstrated by the 3 patients with at least 8Mbp deletions that display profound mental retardation and congenital heart defects. Although haploinsufficiency of the potassium channel beta-subunit (KCNAB2) is thought to be responsible for intractable seizures in the 1p36 deletion syndrome, this was not the case for 3 of the 11 patients in this study. Further investigation of the 1p36 region is necessary to allow identification of genes responsible for the 1p36 deletion syndrome.

We present a boy and two girls with paternal uniparental disomy of chromosome 14q (patUPD14). One girl had a Robertsonian translocation, whereas two a normal karyotype. Based on the manifestations of these patients and four previously reported patients who all had translocated chromosome 14, The patUPD14 was thought to constitute a distinctive syndrome. The hallmarks included abdominal muscular defects, skeletal anomalies, and characteristic facies. The phenotype of patUPD14 was consistent with that of a previously reported mouse model, i.e., mouse embryos with paternal uniparental disomy of chromosome 12 that has a region orthologous to that of human chromosome 14. Dose effects of newly recognized imprinted genes on human chromosome 14q32, DLK1 and GTL2, could play an important role in the pathogenic mechanism of the distinctive malformation complex.

Shwachman-Diamond syndrome is a rare genetic disorder of unknown pathogenesis involving exocrine pancreatic insufficiency and hematological and skeletal abnormalities. There is broad clinical variability; the extent of heterogeneity is unknown but comparisons within a large cohort of patients show no striking differences between patients of families with single or multiple affected offspring. Segregation analysis of a cohort of 69 families has suggested an autosomal recessive mode of inheritance. A single constitutional de novo chromosome rearrangement was reported in a Japanese patient involving a balanced translocation, t(6;12)(q16.2;q21.2), thereby suggesting possible loci for a genetic defect. Evenly spaced microsatellite markers spanning 26-32 cM intervals from D6S1056 to D6S304 and D12S375 to D12S346 were analyzed for linkage in members of 13 Shwachman-Diamond syndrome families with two or three affected children. Two-point lod scores were calculated for each marker under assumptions of recessive inheritance and complete penetrance. Negative lod scores indicated exclusion of both chromosome regions. Further, affected sibs were discordant for inheritance of chromosomes in most families based on constructed haplotypes. The cytogenetic abnormality is not associated with most cases of Shwachman-Diamond syndrome.

We report on a 6-year-old girl with SPONASTRIME dysplasia, characterized by short-limbed dwarfism, a relatively large head, midfacial hypoplasia, a saddle nose, moderate deformities of the vertebral bodies, striated metaphyses, and normal intelligence. She showed severe skeletal changes including marked delay of epiphyseal ossification, evident metaphyseal dysplasia, and osteopathia striata more pronounced than in most of the previously reported patients with this disorder. The patient we describe and a male patient reported by Camera et al. [1994: Pediatr Radiol 24:322–324] are likely to represent the severely-affected end of the clinical spectrum of the disorder. These findings thus rule out the X-linked mode of inheritance of the disorder proposed by Camera et al. [1994: Pediatr Radiol 24:322–324]. Alternatively, the two severely-affected patients may represent a variant form of the disorder. There is evidence that SPONASTRIME dysplasia is a genetically heterogeneous disorder. © 1996 Wiley-Liss, Inc.

Using data compiled from 216,707 births from the population-based Kanagawa Birth Defects Monitoring Program (KAMP), we conducted a case-control study to evaluate the effect of maternal smoking and/or drinking during pregnancy on the risk of infants' anal atresia in 1989-1994. The frequency of maternal smoking (including passive smoking) and/or maternal drinking during pregnancy among 84 infants with anal atresia was compared with 174 matched controls. The 84 anal atresias include 49 cases of isolated anal atresia and 35 cases of syndromal anal atresia. Our findings suggest that maternal drinking during early pregnancy is associated with an increased risk of isolated anal atresia (OR = 4.8, 95% CI 1.2 to 19.1, p0.05). A slightly increased trend was also observed in the association of maternal smoking during pregnancy with both in the pooled groups of anal atresia (OR = 1.4, 95% CI 0.5 to 3.6).

Limb-body wall complex is a malformation of body and limbs with craniofacial defects. We describe here the epidemiology of this complex using the population-based registry data in the Kanagawa Birth Defects Monitoring Program during the period 1982-1991. Eleven infants (11/428,599 births) with the complex were ascertained in the study. The incidence and spectrum of the defects observed in our cases were similar to those of other studies. The parental ages in the study group were not significantly different from those in the general population. No teratogenic agents and factors were identified in the present study. Most cases were diagnosed prenatally.

A confocal laser scanning microscopic system was used to detect the storage of ganglioside GM2 in Tay-Sachs fibroblasts and amniocytes. The diagnosis of the disease was confirmed by counting immunoreactive cells or by digital imaging analysis. This novel system facilitates the prenatal diagnosis of GM2-gangliosidosis.

The diagnosis of Duchenne muscular dystrophy (DMD) has been drastically improved by recent advances in DNA analysis. The Southern blot hybridization using the cDNA 8 probe and the restriction enzyme Hind III was conducted in a gravida and her family in blood samples. The diagnosis revealed partial gene deletions in both the gravida and the DMD-affected second child. The prenatal diagnosis was performed by studying the PCR (polymerase chain reaction) for target DNAs of exons 48 and 51 that correspond with cDNA 8 probe. In the affected child, the 506 bp band at exon 48 was detected but 388 bp at exon 51 was missing. On the other hand, both the 506 bp band at exon 48 and the 388 bp band at exon 51 were detected in the cultured amniotic cells. Thus, the fetus was determined to be not affected.

A female patient with unilateral gonadal dysgenesis was a mosaic for three cell lines, 45,X/46,X, + marI/46,X, + marII, including two different marker chromosomes. DNA analysis using 17 Y-specific DNA probes revealed that each marker consists of different segments of the Y chromosome.

We describe a girl with typical Rubinstein-Taybi syndrome with apparently balanced reciprocal translocation between chromosome 2 and 16. The patient has a condition characterized by mental retardation, typical facial manifestations, broad thumbs and first toes. Cytogenetic studies of the patient showed a reciprocal translocation without visible deletion, karyotype: 46,XX, t(2;16)(p13.3;p13.3). Her parents had normal chromosomes. These results suggest that the locus of the gene for the Rubinstein-Taybi syndrome may be situated at 2p13.3 or 16p13.3.

DNA deletion studies using 5 DNA markers localized at 15q11-q12 were performed in 14 Angelman syndrome (AS) patients (9 sporadic and 5 familial cases). A one-copy density for one or more of the 5 loci was detected in 8 (57.1%) of the 14 patients. A deletion of only the D15S11 locus was detected in one sporadic patient, that involving only the D15S10 in 3 familial patients (sibs in a family), that spanning 3 loci (D15S11, D15S10, D15S12) in one sporadic patient, and that spanning 4 loci (D15S9, D15S11, D15S10, D15S12) in the other 3 sporadic patients. The deletion common to our patients as well as to the reported patients may be confined to a segment between D15S11 and D15S10, if the 5 loci are ordered as cen-D15S18-(D15S9-D15S11-D15S10)-D15S12-qt er. This site overlaps but is more distal to the common deletion site in Prader-Willi syndrome (PWS) patients. In the family of the 3 sibs, both of the phenotypically normal mother and maternal grandfather also have deletions of the D15S10 locus. These results were consistent with the genomic imprinting hypothesis for the occurrence of AS, i.e., the lack of a maternally derived locus leads to AS, but may not support a model that AS is the alternative phenotype of PWS at the identical locus.

We report on two new patients who had unilateral microphthalmia and esophageal atresia. A similar association was previously described in six patients. The accumulation of the eight affected patients provides further support for recognizing this association as a distinct syndrome.

We present two patients with multiple characteristics that occur in Noonan phenotype and cavernous hemangioma of the brain. The first patient, who had been diagnosed radiographically as having a cavernous hemangioma in the left basal ganglia at age 15 years, developed massive intracerebral hemorrhage, resulting in sudden death at home at 19 years. The second patient, who was diagnosed radiographically as having a cavernous hemangioma in the left parietal lobe at age 17 years, is being followed carefully (the patient is currently 18 years old). A review disclosed four cases of structural cerebrovascular abnormalities with or without subsequent hemorrhage. Neither these four patients nor our two patients had any severe anomalies in the heart or large vessels, which are frequently seen in patients with Noonan syndrome. Cerebrovascular abnormalities might have a significant influence on the prognosis of patients with Noonan syndrome, especially those having no severe abnormalities in the heart or large vessels.

Six patients, including two sibs, with Angelman syndrome (AS; three females and three males, aged 11 to 18 years) were studied cytogenetically. Molecular analysis was also performed. Using high-resolution banding technique, we detected a microdeletion in the proximal region of chromosome 15q in four cases. The deleted segment was heterogenous between these patients, and the common deleted region appeared to be 15q11.2. Four patients with deleted 15q were all sporadic cases, whereas in the sib cases we could not detect a visible deletion in the long arm of chromosome 15. However, there was no clinical difference between sporadic cases and sib cases. Densitometric analysis of autoradiographic bands of Southern hybridization using two DNA segments, pML34 and pTD3-21, as probes demonstrated that two patients had only one copy for each of the probes. In the remaining four patients, including the sibs, two copies of each sequence were retained. The probes used here detect a molecular deletion in most Prader-Willi syndrome patients. Thus the segment causing AS is localized adjacent to the critical segment of Prader-Willi syndrome. There seemed to be heterogeneity for the molecular deletion within AS individuals.

Trisomy 18 is a common chromosome anomaly. The predominance of female infants is widely accepted in the literature. This study clarified no sex differences in 18 trisomy births.

Kabuki make-up syndrome is a mental retardation—malformation syndrome affecting multiple organ systems, with a broad spectrum of neuromuscular dysfunction and mental ability. The incidence of seizures associated with this syndrome ranges from 10 to 40%. However, details of the seizures in this syndrome have not been adequately reported or thoroughly evaluated. In this study, we analyzed seizure characteristics and clinical outcomes in nine patients with Kabuki make-up syndrome. Four patients had generalized seizures and two patients had complex partial seizures, extended to secondary generalized seizures. West's syndrome, complex partial seizure, and atonic seizure were seen in one case each, respectively. Electroencephalograms showed focal spikes in seven cases, diffuse spike and wave burst in one case, and hypsarrhythmia in one case. Seizures were well controlled in eight cases and incompletely controlled in only one case. Together with mental retardation, epilepsy can be a primary feature of Kabuki make-up syndrome. Epilepsy associated with Kabuki make-up syndrome is mainly localization-related epilepsy with a favorable seizure outcome. ( J Child Neurol 2003;18:549—551).

We describe a de novo balanced reciprocal translocation between the long arms of chromosomes 5 and 8 [46,XX,t(5;8)(q35;q24.1)] in a 15-month-old girl with a typical Sotos syndrome phenotype. Involvement of the 5q35 region was previously reported (Maroun et al. [1994: Am J Med Genet 50:291-293]) as one of translocation breakpoints in the present patient. We suggest that the gene responsible for Sotos syndrome is located to a distal long-arm region of chromosome 5.

We report on a four-month-old girl with a de novo trisomy 16q [47,XX,+del(16)(p11.2).ish del(16)(p11.2)(wcp16+,D16Z2+,tel16q+, tel16p−)]. She had minor facial anomalies, limb anomalies, urogenital abnormalities, and severe cardiovascular defects. Autopsy confirmed left hypoplastic lung, total anomalous pulmonary venous drainage via coronary sinus, persistent left superior vena cava, patent ductus arteriosus, secundum atrial septal defect, bilateral hydronephrosis and hydroureters, uterus bicornis, and ovarian hypoplasia. Short tandem repeat polymorphism analysis indicated that the additional, structurally abnormal chromosome 16 was maternal in origin. Am. J. Med. Genet. 92:308–310, 2000. © 2000 Wiley-Liss, Inc.

We report a Japanese girl with brachycephaly, a wide forehead, hypertelorism, macroblepharon with eyelid colobomas, ectropion, a broad nasal root, a depressed nasal tip, macrostomia, a small and grooved chin, ear anomalies, a structural anomaly of the corpus callosum, dilatation of the fourth ventricle, a urogenital sinus, and mental retardation. Cause and inheritance are unknown.

Apple peel intestinal atresia is an apple-peel-appearing bowel obstruction of unknown cause. We describe a Japanese girl with the apple-peel jejunal atresia associated with apparently balanced reciprocal translocation between chromosomes 2 and 3, t(2;3)(q31. 3;p24.2)mat. The translocation breakpoints in the patient may become candidate regions for the putative gene causing apple-peel atresia. Alternatively, the association of the two abnormalities in the patient is coincidental because her phenotypically normal mother had the same chromosome translocation.

Young-Simpson syndrome is a rare congenital disorder, characterized by congenital hypothyroidism, congenital heart defects, facial dysmorphism, cryptorchidism in males, hypotonia, mental retardation, and postnatal growth retardation. We describe the cases of a 5-year-old boy and a 7-year-old girl with a similar constellation of symptoms and compared them with previously reported patients.

We describe a male patient with holoprosencephaly, ectrodactyly, cleft lip/cleft palate and hypertelorism. This rare association has previously been reported in two patients. We present a third case and propose a new association representing a distinguishable entity.

We report on a 3-month-old girl with Miller-Dieker syndrome resulting from a maternal full-cryptic translocation t(10;17)(q26.3;p13.3) detectable only by using fluorescence in situ hybridization (FISH). Parental studies using FISH are crucial for genetic counselling in cases of Miller-Dieker syndrome with submicroscopic deletion at 17p13.3. In a family with a parental cryptic translocation and high recurrence risk, prenatal diagnosis using FISH is feasible. © 1995 Wiley-Liss, Inc.

We describe a further patient with the Coffin-Siris syndrome who presented at 4 months with recurrent hypoglycemia attacks. Detailed examination was undertaken at 7 months but the cause of hypoglycemia was not detected. Hypoglycemia seems to be a previously undescribed finding in the Coffin-Siris syndrome.

We report on a boy with Rieger syndrome, who had an apparently balanced reciprocal translocation between chromosomes 1 and 4. The clinical manifestations of this patient were characterized by irregular shaped pupils with a prominent Schwalbe line and an umbilical hernia. On cytogenetic studies, he was found to have a de novo reciprocal translocation 46,XY,t(1;4) (q23.1;q25), without visible deletion. His parents had normal chromosomes. A review of both cytogenetic and genetic linkage analyses with Rieger syndrome showed that chromosome 4q was involved. This and other previous reports suggested that the gene for Rieger syndrome is mapped to the 4q25-->4q26 segment adjoining the breakpoint.

Setleis syndrome is characterized by bitemporal skin depressions resembling forceps marks, abnormalities of the eyelashes, and "leonine" facial appearance. The cause is unknown, although autosomal recessive inheritance has been proposed. Recently, two families were reported in which one of the parents of a patient with Setleis syndrome showed mild manifestations, suggesting autosomal dominant inheritance. We describe a 9-month-old Japanese boy with typical Setleis syndrome. His father, who has normal intelligence, has bitemporal focal dermal dysplasia but a normal face. His paternal second cousin also has Setleis syndrome. This family shows autosomal dominant inheritance including father-to-son transmission of Setleis syndrome with variable expressivity and reduced penetrance. Careful examination of the relatives of patients with Setleis syndrome is recommended.

In a series of 25 Japanese patients with Rubinstein-Taybi syndrome, we screened, by high-resolution GTG banding and fluorescence in situ hybridization of a cosmid probe (RT1, D16S237), for microdeletions associated with this syndrome. In one patient, a microdeletion was demonstrated by in situ hybridization, but none were detected by high-resolution banding.

We analyzed 61 Angelman syndrome (AS) patients by cytogenetic and molecular techniques. On the basis of molecular findings, the patients were classified into the following 4 groups: familial cases without deletion, familial cases with submicroscopic deletion, sporadic cases with deletion, and sporadic cases without deletion. Among 53 sporadic cases, 37 (70%) had molecular deletion, which commonly extended from D15S9 to D15S12, although not all deletions were identical. Of 8 familial cases, 3 sibs from one family had a molecular deletion involving only 2 loci, D15S10 and GABRB3, which define the critical region for AS phenotypes. The parental origin of deletion, both in sporadic and familial cases, was exclusively maternal and consistent with a genomic imprinting hypothesis. Among sporadic and familial cases without deletion, no uniparental disomy was found and most of them were shown to inherit chromosomes 15 from both parents (biparental inheritance). A discrepancy between cytogenetic and molecular deletion was observed in 14 (26%) of 53 patients in whom cytogenetic analysis could be performed. Ten (43%) of 23 patients with a normal karyotype showed a molecular deletion, and 4 (13%) of 30 patients with cytogenetic deletion, del(15) (q11q13), showed no molecular deletion. Most clinical manifestations, including neurological signs and facial characteristics, were not distinct in each group except for hypopigmentation of skin or hair. Familial cases with submicroscopic deletion were not associated with hypopigmentation. These findings suggested that a gene for hypopigmentation is located outside the critical region of AS and is not imprinted.

A 5-year-old boy, who had pre- and postnatal growth retardation, delayed motor development, cutis laxa, delayed closure of large fontanels, congenital hip dislocation and characteristic facies, is described. Disorders with cutis laxa are now divided into five types. The patient had clinical manifestations very similar to those of cutis laxa with bone dystrophy (type II autosomal recessive cutis laxa). Eighteen patients have been reported, the ratio of males to females being 5 to 14. This is the fifth case of this disorder occurring in a male, which provides further evidence for autosomal recessive inheritance.

A case report of a 3-year-old girl with Kabuki make-up syndrome (KMS) associated with anovestibular fistula is presented. To our knowledge, 62 patients with KMS have been reported in the literature, three of whom were described as having an anorectal anomaly. Including the present patient, all four KMS patients were females with anovestibular fistula.

We describe a 22-month-old Japanese girl with severe microcephaly with a prominent nose and a receding chin, developmental delay, marked intrauterine and postnatal dwarfism with limb shortening and brachydactyly, and distinctive radiological changes of the skeleton. The radiological findings include hypoplasia of the short tubular bones, multiple pseudoepiphyses in the bases of the metacarpals, coxa valga, a wide pelvis with iliac flaring, thoracolumbar scoliosis, and disharmonious ossification delay. The clinical and radiological features are somewhat different from those of previously reported cases with osteodysplastic primordial dwarfism. The clinical and radiological manifestations of osteodysplastic primordial dwarfism are reviewed and compared with those in our patient.

Thyroid function was studied in five patients with ring chromosome 18 [r(18)] syndrome and in their mothers. Three of the five patients were clinically or subclinically hypothyroid and had an elevated anti-thyroid antibody (ATA) titer. Another patient had a goiter with the histology showing Hashimoto's thyroiditis. Two mothers of the five patients had an elevated ATA titer, one of whom was subclinically hypothyroid. Our findings indicate that autoimmune thyroiditis may occur with high frequency among patients with r(18) syndrome and their mothers. Thus thyroid function tests are always recommended in patients with the syndrome and their mothers.

This report concerns 844 children with Down syndrome under 15 years of age. Of the 844 cases with Down syndrome, 1.4% have epilepsy at the present time. The types of seizures are as follows; infantile spasms in 4 cases (30.8%), generalized tonic-clonic convulsions in 6 (46.1%), Lennox-Gastaut syndrome in 1 (7.7%) and psychomotor seizure in 2 (15.4%). The onset of seizure was high in the first two years (73. 7%). The occurrence of epilepsy in Down syndrome in childhood did not differ from that in the general population, but infantile spasms were more prevalent in Down syndrome.