A new GNPAT variant of foetal rhizomelic chondrodysplasia punctata.

BACKGROUND: Rhizomelic chondrodysplasia punctata (RCDP) is a clinical entity resulting from defects of peroxisomal metabolism whose clinical phenotype is characterized by rhizomelia, calcified foci in periarticular cartilage, coronal lesions of vertebral bodies, cataracts and severe cognitive delay. Usually, survival does not exceed the first decade of life. Transmission is autosomal recessive and is related to mutations in the PEX7, GNPAT or AGPS. METHODS: A detailed description of the prenatal ultrasound signs of RCDP found in two successive pregnancies in a consanguineous couple is reported. Molecular genetic investigations included the study of the coding regions and the exon-intron junctions of the GNPAT (high-throughput amplification and sequencing performed with Roche NimbleGen SeqCap Target kit on Illumina platform); the confirmation test was carried out by amplification and Sanger sequencing with automatic capillary sequencer. RESULTS: In addition to the typical prenatal ultrasound signs described in the literature in association with RCDP, the presence of prefrontal oedema, never previously described, has been detected in both pregnancies. Moreover, genetic investigations have found a new splicing variant c.924+1G>A of the homozygous GNPAT. CONCLUSION: The role of mutation in the GNPAT suggests a likely association with the clinical phenotype.

Neurosurgical treatment of subependymal giant cell astrocytomas in tuberous sclerosis complex: a series of 44 surgical procedures in 31 patients.

BACKGROUND: Subependymal giant cell astrocytomas (SEGA) are benign tumors characteristic of tuberous sclerosis complex (TSC) that may cause hydrocephalus. Various treatments are nowadays available as mTOR inhibitors or surgery. Surgery is still a valid option especially for symptomatic and larger tumors. METHODS: From January 1994 to December 2015, 31 TSC patients harboring SEGA underwent surgery at the Department of Neurosurgery of the Meyer Pediatric Hospital, Florence. Indications for surgery were tumor size and location, growth and cystization/hemorrhage, and hydrocephalus. Clinical data, preoperative and postoperative MRI, recurrence rate, further surgical procedures, and related complications were analyzed. RESULTS: A total of 44 surgeries were performed in 31 TSC patients affected by SEGA, achieving gross total removal (GTR) and subtotal removal (STR), respectively, in 36 and 8 patients. Recurrences occurred in 11 patients; 9 of them underwent further surgical procedures and 2 were treated with mTOR pathway inhibitors. Surgical morbidity and mortality were, respectively, 22.7% and 2.3%. After a mean follow-up of 4.9 years, 90% of patients were tumor-free with good neurological status in 93.3%; twelve (40%) had a ventriculo-peritoneal shunt (VPS) for hydrocephalus. CONCLUSIONS: The present series confirms that the surgical approach, combined with mTOR inhibitors, is still a valid option for the treatment of SEGAs.

Metatropic dysplasia in third trimester of pregnancy and a novel causative variant in the TRPV4 gene.

Prenatal diagnosis of skeletal dysplasias is particularly difficult for many reasons and differentiating these disorders in the prenatal period can be challenging because they are rare and many of the ultrasound findings are not necessarily pathognomonic for a specific disorder. The diagnosis is often made just after birth or exitus. The prenatal diagnosis of osteochondrodysplasias is based predominantly upon fetal ultrasound findings and it focuses substantially on the possible lethality of the disorder, without always being able to find a specific name for the disorder. Metatropic dysplasia is a rare osteochondrodysplasia due to mutations in the TRPV4 gene: TRPV4 is a cation channel, non-selectively permeable to calcium, encoded by a gene on chromosome 12q24.11; it is widely expressed and involved in many different physiological processes through responses to several different stimuli (physical, chemical, and hormonal) in ciliated epithelial cells. The exact incidence of this disorder is not known, however less than a hundred cases have been reported at present, with only two prenatal reports but without any reference to the molecular test. We describe the first report of molecular diagnosis of metatropic dysplasia carried out in prenatal diagnosis: the molecular testing of the TRPV4 (transient receptor potential cation channel, subfamily V, member 4, MIM *605427) gene in our case, in fact, detected a causative variant, confirming the diagnostic suspicion, which was made possible thanks also to the utilization of MRI and CT scan. In our case different imaging methods together with the close cooperation of a multidisciplinary team and test availability, allowed an accurate diagnosis.

Prenatal diagnosis of X-linked adrenoleukodystrophy associated with isolated pericardial effusion.

This is the first reported case of fetal pericardial effusion in association with X-linked adrenoleukodystrophy and hypocortisolism from a nonautoimmune cause. Our hypothesis is that in experienced hands and after accurate genetic counseling, isolated pericardial effusion can constitute an indication for a severe metabolic disease.

Early postnatal doppler assessment of cerebral blood flow velocity in healthy preterm and term infants.

The aim of the present study was to generate normal reference data for anterior and middle cerebral artery blood flow velocity and resistance index in preterm and term infants during the first 8 hours of life. The study population longitudinally included 120 healthy preterm and term infants (gestational age 24 to 41 weeks), all of appropriate weight for gestational age. The following parameters were studied: peak-systolic velocity, end-diastolic velocity, mean velocity, and resistance index. All parameters were measured in the anterior cerebral artery, in the left middle cerebral artery, and in the right middle cerebral artery with the use of Doppler colour ultrasonography. In addition, we studied the ratio of mean arterial blood pressure to mean velocity in the three cerebral arteries as a further estimate of cerebral relative vascular resistance. We found that cerebral blood flow velocities increased significantly with increasing gestational age and birthweight, both in the anterior cerebral artery and in the right and left middle cerebral arteries. Resistance index, both in the anterior cerebral artery and in the middle cerebral arteries, increased significantly only with increasing gestational age. Relative vascular resistance decreased significantly with increasing gestational age and birthweight in the three cerebral arteries. Significant differences were found (p<0.05) in these values between the anterior cerebral artery and the middle cerebral arteries. The narrow time frame (2 to 8 hours) that we used to evaluate cerebral blood flow velocity often represents a significant moment at which decisions are made that can be fundamental for the outcome of the newborn infant.

Umbilical cord care: the effect of eight different cord-care regimens on cord separation time and other outcomes.

In this study we evaluate the effect of eight cord-care regimens on cord separation time and other secondary outcomes: omphalitis, sepsis, death, cord bleeding, compliance, satisfaction or dissatisfaction with regard to the type of treatment, umbilical cord colonization--in 1,535 healthy term infants. The eight cord-care regimens studied were: 70% alcohol, natural drying, salicylic sugar powder, triple dye, micronized green clay powder, colloid silver-benzyl-peroxide powder, neomycin-bacitracin powder, 1% basic fuchsine. None of the newborns developed sepsis or died and we found only sporadic cases of omphalitis. With regard to cord separation time the best results were obtained with salicylic sugar powder (5.6 +/- 2.3 days) and green clay powder (6.7 +/- 2.2 days). Both forms of treatment proved to be more effective (p < 0.05) than all the others. We found that salicylic sugar powder allows for early cord detachment resulting in excellent parent treatment compliance and reduction of their concern, notwithstanding higher percentages of cord bleeding. The rate of positive umbilical swabs was low and was significantly higher only than the results obtained with neomycin-bacitracin powder treatment. This study demonstrates that, in hospital nurseries of developed countries, salicylic sugar powder can be effectively and safely used for umbilical cord care of healthy term infants.