Beckwith-Wiedemann syndrome: difficulties with prenatal diagnosis

The characteristics of the midsole were examined in four pairs of running shoes by a materials test. The variables of interest were the peak acceleration, time to peak acceleration and the kinetic energy absorbed. Ten subjects then ran at a recreational jogging pace (3.5 ms-1) barefoot and in the shoes. An accelerometer secured to the lower tibia was used to measure the peak acceleration and time to peak acceleration associated with footstrike. Subjects were also videoed and a kinematic analysis was undertaken at the knee and ankle joints. The results from the materials test showed that the shoes differed in their midsole characteristics, however, no significant differences (P > 0.05) were observed in the peak acceleration and time to peak acceleration during running in shoes. These variables were significantly greater in the barefoot running condition (P < 0.05), as compared with running in shoes. Small and subtle kinematic differences were observed between the barefoot and shoe conditions. It appears that the differences observed between the shoes in the materials test were not sufficient to elicit the kinematic changes observed between the barefoot and shoe conditions. It is suggested that runners operate within a 'kinetic bandwidth' when responding to impact stresses.     

Renal cell carcinoma in a patient with Beckwith-Wiedemann syndrome

We report the case of a patient with Beckwith-Wiedemann syndrome (BWS) who developed renal cell carcinoma (RCC). At birth, this patient presented with macroglossia, diastasis recti, mild gigantism, hepatomegaly and hypoglycemia, and the diagnosis of BWS was made. At 22 months, an intrapelvic rhabdomyosarcoma was detected and resected. At 37 months, computed tomography (CT) demonstrated a small mass with high attenuation in the right kidney, which was surgically confirmed to be RCC.     

Cranial ultrasound and CT findings in infants with hypernatremic dehydration

We present two newborn infants with hypernatremic dehydration with central nervous system (CNS) involvement. Both patients showed similar imaging findings, demonstrating generalized brain parenchymal abnormality and multifocal areas of hemorrhage or hemorrhagic infarction. These findings are compatible with previously described CNS pathologic findings in hypernatremia.     

Medullary renal dysplasia mimicking renal tumor in the Beckwith-Wiedemann syndrome

The known association of Wilms' tumor with the Beckwith-Wiedemann syndrome has prompted a surveillance regimen for children with this problem. Herein we report a case of medullary renal dysplasia that was a new onset by documented ultrasound. The association of medullary renal dysplasia with Beckwith-Wiedemann syndrome is discussed as well as the management of this problem.     

Intrauterine growth retardation associated with hypoxia due to bronchiectasis

Two pregnancies in a young patient who had undergone lobectomy for bronchiectasis are described. Both were complicated by intrauterine growth retardation. The only abnormality detected was maternal hypoxaemia, and this was assumed to be causal.     

Low frequency of p57KIP2 mutation in Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome (BWS) is an autosomal dominant disorder of increased prenatal growth and predisposition to embryonal cancers such as Wilms tumor. BWS is thought to involve one or more imprinted genes, since some patients show paternal uniparental disomy, and others show balanced germ-line chromosomal rearrangements involving the maternal chromosome. We previously mapped BWS, by genetic linkage analysis, to 11p15.5, which we and others also found to contain several imprinted genes; these include the gene for insulin-like growth factor II (IGF2) and H19, which show abnormal imprint-specific expression and/or methylation in 20% of BWS patients, and p57KIP2, a cyclin-dependent kinase inhibitor, which we found showed biallelic expression in one of nine BWS patients studied. In addition, p57KIP2 was recently reported to show mutations in two of nine BWS patients. We have now analyzed the entire coding sequence and intron-exon boundaries of p57KIP2 in 40 unrelated BWS patients. Of these patients, only two (5%) showed mutations, both involving frameshifts in the second exon. In one case, the mutation was transmitted to the proband's mother, who was also affected, from the maternal grandfather, suggesting that p57KIP2 is not imprinted in at least some affected tissues at a critical stage of development and that haploinsufficiency due to mutation of either parental allele may cause at least some features of BWS. The low frequency of p57KIP2 mutations, as well as our recent discovery of disruption of the K(v)LQT1 gene in patients with chromosomal rearrangements, suggest that BWS can involve disruption of multiple independent 11p15.5 genes.     

Intrauterine growth restriction: identification and management

Intrauterine growth restriction (IUGR) is a common diagnosis in obstetrics and carries an increased risk of perinatal mortality and morbidity. Identification of IUGR is crucial because proper evaluation and management can result in a favorable outcome. Certain pregnancies are at high risk for growth restriction, although a substantial percentage of cases occur in the general obstetric population. Accurate dating early in pregnancy is essential for a diagnosis of IUGR. Ultrasound biometry is the gold standard for assessment of fetal size and the amount of amniotic fluid. Growth restriction is classified as symmetric and asymmetric. A lag in fundal height of 4 cm or more suggests IUGR. Serial ultrasonograms are important for monitoring growth restriction, and management must be individualized. General management measures include treatment of maternal disease, good nutrition and institution of bed rest. Preterm delivery is indicated if the fetus shows evidence of abnormal function on biophysical profile testing. The fetus should be monitored continuously during labor to minimize fetal hypoxia.     

Bone invasion by a recurrent digital fibroma of infancy in a child with Beckwith-Wiedemann syndrome

We describe a child with features of the Beckwith-Wiedemann syndrome with congenital recurrent digital fibroma of infancy that extended into and replaced the marrow of the terminal phalynx of the little finger. Digital fibromas of infancy have not previously been associated with either Beckwith-Wiedemann syndrome or invasion into underlying bone.     

IGF2 is parentally imprinted during human embryogenesis and in the Beckwith-Wiedemann syndrome

The phenomenon of parental imprinting involves the preferential expression of one parental allele of a subset of chromosomal genes and has so far only been documented in the mouse. We show here, by exploiting sequence polymorphisms in exon nine of the human insulin-like growth factor 2 (IGF2) gene, that only the paternally-inherited allele is active in embryonic and extra-embryonic cells from first trimester pregnancies. In addition, only the paternal allele is expressed in tissues from a patient who suffered from Beckwith-Wiedemann syndrome. Thus the parental imprinting of IGF2 appears to be evolutionarily conserved from mouse to man and has implications for the generation of the Beckwith-Wiedemann syndrome.     

Dental findings in an adult with Lowe's syndrome

This paper describes the dental findings and care of a Chinese adult affected with oculo-cerebro-renal syndrome--Lowe's syndrome--a rare, X-linked recessive disorder, whose clinical manifestations include cataracts, mental retardation, and renal tubular dysfunction. Approximately 150 cases have been reported in the last 45 years. Little has been reported in the dental literature. This patient is described with particular reference to the dental findings, which include gross periodontal disease with severe bone loss, impaction of teeth in the permanent dentition, taurodontism, and underdevelopment of the maxilla and mandible. Dental treatment was aimed at arresting the periodontal disease and preserving the remaining dentition.     

Cerebellar growth in normal and growth-restricted fetuses of multiple gestations

OBJECTIVE: Our purpose was to evaluate growth of the cerebellum in growth-restricted fetuses of twin and triplet gestations versus growth in normal in utero sibling(s) and in singleton gestations. STUDY DESIGN: An ultrasonographic study was conducted in a population of pregnant women with twin and triplet gestations. The control group was either the normal in utero sibling(s) when one fetus was growth restricted or normal twin and singleton pregnancies. Standard biometric measurements were obtained on all fetuses throughout pregnancy, including the transverse cerebellar diameter. However, only the last measurement was used for the analysis. Statistical analyses were conducted comparing growth of the transverse cerebellar diameter among the growth-restricted fetuses versus growth in the normal in utero fetal sibling(s) or other normal twin and singleton gestations. RESULTS: Pregnancies were categorized on the basis of the growth status of women with twin and triplet gestations: Group 1 (151) contained women with two fetuses appropriately grown for gestational age; group 2 (52) had one appropriately grown fetus and one with intrauterine growth restriction; group 3 (19) had two fetuses with intrauterine growth restriction. In addition, there were 30 triplet gestations (group 4), five of which had growth-restricted fetuses, and group 5 contained 1405 singleton pregnancies. In all five groups there was a statistically significant relationship between transverse cerebellar diameter and gestational age (p < 0.0001). There was also no significant difference between growth of the transverse cerebellar diameter in the appropriately grown and growth-restricted siblings and among normal singleton and twin pregnancy groups. In most cases of growth-restricted fetuses, except for the transverse cerebellar diameter measurements, all other biometric parameters were < 10th percentile. CONCLUSION: These data confirm the relative preservation of normal cerebellar growth in growth-restricted fetuses and a similar rate of growth in singleton and multifetal gestations. The transverse cerebellar diameter therefore represents an independent biometric parameter that can be used in both singleton and multifetal pregnancies to assess normal and deviant fetal growth.     

Morphologic findings in fetuses and placentas of late abortion in the 2nd trimester

To investigate possible causes of abortion (and intrauterine foetal death) we reviewed clinical and morphological data of foetuses and placentas morphologically from 830 spontaneous abortions seen during a 12 years period (1978-1989) at the Institute of Pathology, University of Leipzig, and the Pathological Institute of Hoyerswerda. Our review showed that definite and possible causes of foetal death and abortion could be classified as placental, foetal maternal, and clinical. Placental changes, which included infection of the foetal membranes, disturbances of the uteroplacental circulation (abruptio placentae with bleeding) and placental dysmaturity, were the most important causes and accounted for 73.8% of the cases. Foetal causes mainly comprised multiple twin pregnancies and foetal malformations. In 20 cases (2.4%) we found malformations as a cause of foetal death and consecutive abortion. Overall, malformations were found in 7.5% of the cases examined. Maternal and obstetric complications of pregnancy were less frequent. In 16.5% of our cases, the cause of the abortion or intrauterine death remained obscure. However, since 1989, genetic analysis and prenatal diagnostic procedures have improved, bringing a greater knowledge on the spectrum and aetiology of possible developmental disorders in the foetus. This should reduce the number of unexplained abortions.     

Intrauterine growth retardation of the fetus and the pregnancy

IUGR (intrauterine growth retardation) is a serious complication of pregnancy. The author compared in the submitted paper different diagnostic and therapeutic possibilities in a six-year retrospective group of 181 hypotrophic foetuses. Based on the results he emphasizes the necessity of magnesiotherapy and prevention of IUGR by acylpyrin. It is impossible to monitor and treat adequately a pregnant woman with a hypotrophic foetus without Doppler sonography. Combination of indexes from various areas (brain, umbilicus) is useful. Even the somewhat obsolete method of assessment of estriol in the urine of pregnant women should not be refuted. Even during the present period of transformation of health services IUGR therapy under ambulatory conditions is not recommended. The author emphasizes the comprehensive character of evaluation of all diagnostic methods for the detection of IUGR.     

Clinical findings in Brown-McLean syndrome

The Brown-McLean syndrome is a clinical condition with corneal edema involving the peripheral 2 to 3 mm of the cornea. The edema typically starts inferiorly and progresses circumferentially, but spares the central portion of the cornea. Additionally, the edema is associated with a punctate orange-brown pigmentation on the endothelium underlying the edematous areas. Central cornea guttata is frequently seen. This condition occurs most frequently after intracapsular cataract extraction, but may also occur after extracapsular cataract extraction and phacoemulsification, or pars plana lensectomy and vitrectomy. Surgical complications and multiple intraocular procedures are frequently observed in these patients. Less frequently, the Brown-McLean syndrome can occur in eyes that have not had surgery. We studied the clinical characteristics of 43 affected eyes of 32 patients. New findings included Brown-McLean syndrome occurring in two eyes of a phakic patient with intermittent angle-closure glaucoma. Two eyes developed Brown-McLean syndrome after phacoemulsification and one eye developed peripheral edema after pars plana vitrectomy and lensectomy. Additionally, severe, infectious keratitis occurred after rupture of peripheral bullae in two eyes. Patients with this condition should be examined periodically and educated regarding the early clinical signs of corneal ulceration.     

MR findings in oculocerebrorenal syndrome

Oculocerebrorenal syndrome is an X-linked recessive disorder characterized by congenital ocular abnormalities, mental retardation, renal disease, and metabolic bone disease. We report a case of oculocerebrorenal syndrome and, using T1-, proton density-, and T2-weighted imaging sequences, are able to characterize two distinct white matter abnormalities: one lesion is punctate and has signal characteristics that parallel that of cerebrospinal fluid; a second lesion, found in association with the first, consists of patchy white matter abnormalities that are hypointense on T1-weighted images but hyperintense on proton density- and T2-weighted images.     

Microbiological and immunohistological findings in a patient with Papillon-Lefèvre syndrome

The following communication is a case history of an 11 year-old female patient suffering from Papillon-Lefèvre syndrome. Since a massive occurrence of A. actinomycetemcomitans had been found in the subgingival microflora of the periodontal pockets, the patient was treated with repeated subgingival scaling, with an adjunct Amoxicillin and Metronidazol treatment. A bacteriological examination of the girl's family proved that several brothers and sisters as well as one parent also carried. A. actinomycetemcomitans, showing 3 different strains of this bacterium within the family. An immunohistological examination of the gingival tissue showed a massive inflammatory infiltrate which was dominated by plasma cells. The histological investigation of the first molars did not show morphological abnormalities of the root cementum. Posttreatment clinical and radiographical improvement of the periodontal conditions is reported despite the recurrent finding of A. actinomycetemcomitans.     

Pelvic ultrasound findings in different forms of sexual precocity

Recently produced reference curves for various ultrasound dimensions were used to retrospectively assess 67 pelvic ultrasound scans carried out at the initial presentation in girls with sexual precocity. At presentation the group with precocious puberty had significantly increased uterine lengths and ovarian volumes compared with the normal population, and a significantly increased fundal-cervical ratio. Ovarian volume was also significantly increased in therlarche and thelarche variant. The fundal-cervical ratio was significantly increased in thelarche variant. There was considerable overlap between individuals with sexual precocity and normal subjects. The ultrasound findings that best discriminated early or precocious puberty from other forms of sexual precocity were the presence of a midline endometrial echo, and a uterine length above the 97th centile for age. An entirely normal pelvic ultrasound at presentation did not rule out the possibility of precocious puberty.     

Subependymal pseudocysts: ultrasound diagnosis and findings at follow-up

During a two-year period, subependymal pseudocysts were diagnosed in 24 infants using cranial ultrasound: 8 were located at the external angle of the lateral ventricle and 16 at the caudothalamic notch. Associated congenital anomalies were present in six infants and CMV was isolated in one case. Four of the eight infants with pseudocysts at the external angle were one half of twins. As all but one of the surviving infants with pseudocysts were normal at follow-up (at 3-24 months of age), it is important to make a distinction between pseudocysts and extensive cystic periventricular leukomalacia, as the latter condition invariably leads to cerebral palsy and/or visual impairment.     

Clinicopathologic findings in the Bannayan-Riley-Ruvalcaba syndrome

BACKGROUND: The term Bannayan-Riley-Ruvalcaba syndrome has been proposed to reflect the clinical overlap of 3 conditions previously described as separate entities, each inherited in an autosomal dominant fashion. They are the Riley-Smith, Bannayan-Zonana, and Ruvalcaba-Myhre-Smith syndromes. OBSERVATIONS: We studied 2 kindreds with the Bannayan-Riley-Ruvalcaba syndrome. Characteristic cutaneous findings included multiple subcutaneous lipomas and vascular malformations, lentigines of the penis and vulva, verrucae, and acanthosis nigricans. Macrocephaly with normal ventricular size, mental retardation, central nervous system vascular malformations, intestinal polyposis, skeletal abnormalities, and thyroid tumors were the most common systemic featues. A striking clinical finding in 1 patient was widespread verrucous changes of both lips that histologically showed epidermal hyperplasia with papillomatosis and hyperkeratosis. Biopsy specimens of facial papules demonstrated the histological features of both syringomas and trichilemmomas. Lentiginous hyperplasia of the epidermis with increased pigment in the basal layer and a slight increase in the number of melanocytes were seen in biopsy specimens of the penile lentigines. CONCLUSIONS: The histologic findings of both the facial lesions and the pigmented macules of the penis in the Bannayan-Riley-Ruvalcaba syndrome have not, to our knowledge, been reported previously. The similarities between the Bannayan-Riley-Ruvalcaba syndrome and Cowden disease raise the possibility of a common genetic pathogenesis for these 2 diseases.