Trisomy 13 mosaicism syndrome with atypical plurimalformative phenotype

Introduction: Orofacial clefts are important congenital malformations of the lip, palate, or both caused by complex genetic and environmental factors. Aims and Objectives: The present study aims to highlight the phenotypic heterogeneity of trisomy 13 mosaicism. Material and Methods: We present one clinical case of a 30-year-old, Caucasian woman who is pregnant for the first time. Techniques of work study: anamnesis, clinical examination, serological tests for Toxoplasmosis, Rubeola, CMV and Herpes, ultrasound examination at 20 weeks gestation with General Electric Echographe Voluson E10 BT18, amniocentesis, fetal chromosome analysis and genetic counseling. Results: Ultrasound examination showed a viable singleton fetus with intra-uterine growth restriction, oligohydramnios, bilateral cleft lip and cleft palate, hypoplastic nasal bone and bilateral polycystic kidneys. Amniocentesis was done, and the fetal chromosomal analysis revealed a fetus with 46, XY/47, XY,+13 mosaic karyotype. After a complex genetic counselling the parents opted, to terminate the pregnancy. The autopsy confirm the prenatal ultrasound diagnosis. Conclusion: Routine ultrasound examination during pregnancy and specific genetic testing are essential for the early prenatal detection of major structural fetal anomalies associated with rare genetic chromosome syndromes.

A histopathological observation made on cystic kidneys obtained from human cadavers

Introduction: Cysts in the kidneys have been described as being heterogeneous, and occur due to hereditary,developmental and acquired disorders. They account for 6-8% of diseases that go for dialysis. Evaluating cysticdiseases is important for pathological diagnosis and treatment procedures for the patient.Objective: Present study aimed at finding the types of cysts prevalent in human cadaveric kidneys by making ahistopathological observation. The study was made to review the incidence of cysts in kidneys and to find outwhat are the commonest types of cysts that are identified.Material and Methods: Thirty formalin fixed adult cadavers were used for the study. Twenty were male and tenwere female cadavers used for routine dissection and teaching purposes for the first year medical students in thedepartment of Anatomy, P.E.S Institute of Medical Sciences and Research. The kidneys were dissected out from thecadavers from both sides. The fat and fascia were removed carefully and first photographed for gross appearance,before handing the specimens to the department of pathology for further study by making sections.Results: Cystic kidneys were seen in seven cadavers out of the thirty cadavers. The other cadavers had no cystickidneys. The incidence of cysts has been calculated in this study as 23.3%. The normal kidneys were 76.6%. Inthree female cadavers unilateral cysts were seen in the right kidney. In male cadavers, one had unilateral cystand the remaining three presented with bilateral cystic kidneys. One among the four showed multiple bilateralcysts ranging from one to forty five cysts.Conclusion: From this study it is evident that cysts of the kidney may occur without disturbing the normalfunctioning of the kidneys. The incidence of multiple cysts was more in males than in females. No of cysts weremore in the right than in the left kidneys. For a person to lead a normal life one fifth of the kidney is sufficient ifit functions normally.

Two cases of TSC2/PKD1 contiguous gene deletion syndrome

Tuberous sclerosis complex (TSC, MIM#191100) is an autosomal dominant neurocutaneous syndrome caused by mutation or deletion of TSC1 encoding hamartin or TSC2 encoding tuberin and characterized by seizure, mental retardation, and multiple hamartomas or benign tumors in the skin, brain, retina, heart, kidney, and lungs. The TSC2 gene on chromosome 16p13.3 lies adjacent to the PKD1 gene which is responsible for autosomal dominant polycystic kidney disease (MIM#173900). The TSC2/PKD1 contiguous gene syndrome (TSC2/PKD1 CGDS, MIM#600273) is caused by deletion of both TSC2 and PKD1 gene. We recently experienced a 15 month-old boy and a 26 month-old girl with TSC2/PKD1 CGDS confirmed by multiplex ligation-dependent probe amplification (MLPA) analysis. They showed not only typical neurologic manifestations of TSC such as epilepsy, subependymal nodules, and subcortical tubers, but also polycystic kidney disease. The contiguous gene syndrome involving PKD1 and TSC2 should be suspected in children with enlarged polycystic kidneys and TSC. MLPA analysis is a useful method for the genetic confirmation of TSC2/PKD1 CGDS.

Meckel’s Gruber With Dandy-Walker Syndrome.

Abstracts: Background: Meckel-Gruber syndrome (MGS) is a classic triad of occipital encephalocele, postaxial polydactyly and dysplastic cystic kidney with or without other associated malformations. Dandy-Walker malformation (DWM) is the association of three signs: hydrocephalus, partial or complete absence of the cerebellar vermis, and posterior fossa cyst contiguous with the fourth ventricle. Methodology: A 30 weeks dead fetus fixed in formalin was sent at Genetic Health And Research Center, Nasik for further evaluation. It was diagnosed by ultrasonography as Dandy walker syndrome with multiple congenital anomalies. Autopsy finding confirmed that it was Meckel’s Gruber syndrome. Results & Discussion: Meckel-Gruber syndrome is extremely heterogenous syndrome with six different loci and it inherits in families as autosomal recessive disease with 25% of chance of recurrence in each pregnancy. MGS affects multiple organ systems of the body leading to many other pathological conditions such as Arnold-Chiari malformation or Dandy-Walker malformation. It is suggested to be caused by failure of the mesodermal induction leading to ciliopathies caused by dysfunction of cilia. The occurrence of a Dandy-Walker malformation in Meckel-Gruber syndrome confirms disturbance in rhombencephalon development and such variants are very uncommon. Many cases of Dandy Walker Syndome as such have been published throughout but Dandy Waker associated with Meckel’s Gruber Syndrome is extremely rare. Conclusion: We propose that proper autopsy of all still birth should be conducted to guide parents for possible risks in subsequent pregnancies. Prenatal and postnatal counseling and prenatal diagnosis should be encouraged in all disease prone cases.

Sirenomelia: Mermaid Syndrome.

A neonate with rare congenital anomalies was born at 25 weeks of gestation and died within 17 minutes of birth. On examination of the baby, it was found that the lower limbs were malrotated and fused all along the length with six toes. External genitalia, urogenital and anal orifices were absent. At autopsy, a single umbilical artery was found arising from the abdominal aorta. Both the kidneys were polycystic and were situated in the iliac fossae. Distal portion of the large gut beyond caecum was absent and rectum was atretic. No reproductive organ was found. On the basis of the findings, the case was diagnosed as sirenomelia (mermaid syndrome).

Caffeine intake by patients with autosomal dominant polycystic kidney disease

Because caffeine may induce cyst and kidney enlargement in autosomal dominant polycystic kidney disease (ADPKD), we evaluated caffeine intake and renal volume using renal ultrasound in ADPKD patients. Caffeine intake was estimated by the average of 24-h dietary recalls obtained on 3 nonconsecutive days in 102 ADPKD patients (68 females, 34 males; 39 ± 12 years) and compared to that of 102 healthy volunteers (74 females, 28 males; 38 ± 14 years). The awareness of the need for caffeine restriction was assessed. Clinical and laboratory data were obtained from the medical records of the patients. Mean caffeine intake was significantly lower in ADPKD patients versus controls (86 vs 134 mg/day), and 63% of the ADPKD patients had been previously aware of caffeine restriction. Caffeine intake did not correlate with renal volume in ADPKD patients. There were no significant differences between the renal volumes of patients in the highest and lowest tertiles of caffeine consumption. Finally, age-adjusted multiple linear regression revealed that renal volume was associated with hypertension, chronic kidney disease stage 3 and the time since diagnosis, but not with caffeine intake. The present small cross-sectional study indicated a low level of caffeine consumption by ADPKD patients when compared to healthy volunteers, which was most likely due to prior awareness of the need for caffeine restriction. Within the range of caffeine intake observed by ADPKD patients in this study (0-471 mg/day), the renal volume was not directly associated with caffeine intake.

Meckel-Gruber Syndrome: An autopsy case

We report an autopsy of a male fetus that showed multiple congenital anomalies that could best be designated as Meckel-Gruber syndrome. The fetus was born dead at the gestational age of 38 weeks. His parents denied any history of congenital malformation. And the parity of the mother was 0-0-0-0, but she had the past history of receiving herb medication for common cold. The congenital anomalies found in this case consited of occipital meningoencephalocele, midline cleft palate, bifid epiglottis, hepatic fibrosis, choledochal cyst, bilateral polycystic kidneys, postaxial polydactyly of both hands and feet, aplasia of the left testis, secundum type atrial septal defect and patent ductus arterious. This malformation syndrome is rare and lethal. The prenatal diagnosis should be made by ultrasound study or analysis of the amniotic fluid for alpha-feto protein during intrauterine period. The kidneys showed Potter type III cystic change and there was a characteristic hepatic fibrosis.