A novel homozygous MCOLN1 double mutant allele leading to TRP channel domain ablation underlies Mucolipidosis IV in an Italian Child.

Mucolipidosis type IV (MLIV) is a very rare disorder of late endosome/lysosome transport, characterized by neurodevelopmental abnormalities and progressive visual impairment owing to corneal clouding and retinal dystrophy. Greater than 70 % of MLIV patients are of Ashkenazi Jewish ancestry. Here we report a novel MCOLN1double mutant allele [c.395_397delCTG;c.468_474dupTTGGACC] which introduces a premature stop codon [p.Ala132del; p.Asn159LeufsX27] leading to almost complete abrogation of the region coding mucolipin-1, a member of the transient receptor potential (TRP) cation channel family. The genomic lesion was identified in homozygous state, in a non-Jewish Italian MLIV patient, who also presented abnormal serum gastrin levels. Conventional and advanced MRI sequences, including diffusion tensor imaging and tractography, were used for the assessment of white matter involvement in the patient.

Long term follow-up in two siblings with Sengers syndrome: Case report.

BACKGROUND: Sengers syndrome is characterized by congenital cataract, hypertrophic cardiomyopathy, mitochondrial myopathy, and lactic acidosis associated with mutations in AGK gene. Clinical course ranges from a severe fatal neonatal form, to a more benign form allowing survival into adulthood, to an isolated form of congenital cataract. Thus far few reported cases have survived the second decade at their latest examination, and no natural history data are available for the disease. CASE PRESENTATION: Here we provide a 20-year follow-up in two siblings with a benign form of Sengers syndrome, expanding the phenotypical spectrum of the disease by reporting a condition of ovarian agenesis. CONCLUSION: To our knowledge, this report provides the first longitudinal data of Sengers syndrome patients.

Validation of the postnatal growth and retinopathy of prematurity screening criteria: A retrospective Italian analysis.

PURPOSE: Retinopathy of prematurity (ROP) is the leading cause of childhood blindness. The aim of our study is to validate the new screening criteria elaborated by the Postnatal Growth and Retinopathy of Prematurity (G-ROP) study group in a monocentric cohort of Italian preterm infants. METHODS: We retrospectively applied the G-ROP screening criteria to a cohort of preterm infants born between May 2015 and July 2020 with known birth weight, gestational age, serial weight measurement, and known ROP outcome. Primary outcomes were sensitivity and specificity of ROP detection, especially of treatment requiring ROP. Secondary outcomes were reduction of ophthalmologic examinations and of infants requiring screening. RESULTS: We retrospectively evaluated 595 children and 475 were included in our study. Of them, 119 developed any type ROP, 39 developed type 1 ROP, and 28 underwent treatment. G-ROP criteria predicted 39 of 39 cases of type 1 ROP (100% sensitivity and specificity). Sensitivity and specificity for detection of treated ROP were 100%. Considering any type ROP detection, sensitivity was 87.4% and specificity was 100%. Our analysis showed that screening could be avoided in 50% of patients, resulting in a 29% reduction of the number of examinations. CONCLUSIONS: Our study validates the new G-ROP screening protocol in a monocentric cohort of premature infants. We demonstrate that all Type 1 ROP and requiring treatment ROP could be found even with a reduction of eye examinations.

Gross enophthalmos after cerebrospinal fluid shunting for childhood hydrocephalus: the "silent brain syndrome".

PURPOSE: To describe the clinical characteristics and ophthalmic management of 2 patients who developed gross enophthalmos after ventriculo-peritoneal shunting performed in their teenage years. A key radiologic feature is presented, and a conjectural mechanism is proposed for this disfiguring condition. METHODS: Retrospective case note review for 2 patients requiring ophthalmic care for gross enophthalmos after prior ventriculo-peritoneal shunting. RESULTS: Two patients, aged 24 and 25 years, presented with severe bilateral enophthalmos, bridging of all the tarsal plates off the ocular surface with secondary upper eyelid entropion, and significant lagophthalmos, associated with diffuse keratopathy. Both patients were of normal body weight, and neither had a history of anorexia nervosa. CT of the orbit revealed gross enophthalmos, with air entrapment between the globe and upper eyelids, together with a marked upward bowing of the orbital roof in the anterior cranial fossa, a newly recorded sign in this condition. One patient underwent bilateral orbital roof implants, and the other had bilateral upper eyelid entropion repair. CONCLUSIONS: Progressive, severe, bilateral, symmetrical enophthalmos with bridging of the eyelids across the ocular surface due to upward bowing of the orbital roof many years after venticulo-peritoneal shunt in the absence of symptomatic intracranial disease are pathognomonic features of the "silent brain syndrome." A common feature was shunting in the early teenage years; although the enophthalmos had been noted for several years before presentation, the corneal symptoms had only become troublesome enough to seek ophthalmic care in their third decade, and the speed of development for this condition remains unclear. The authors suggest that a sudden reduction of raised intracranial pressure causes an "implosion" of the only available thin cranial bone-namely, the frontal plate of the orbit. Such remodeling might be greater if the bone was still relatively unmineralized, because of youth or preceding hydrocephalus. The expansion of orbital volume is responsible for the characteristic clinical features and symptoms and can be treated with placement of appropriately sized orbital roof implants or, if this is not desired, by upper eyelid entropion repair.

Automated microseismic event location using Master-Event Waveform Stacking.

Accurate and automated locations of microseismic events are desirable for many seismological and industrial applications. The analysis of microseismicity is particularly challenging because of weak seismic signals with low signal-to-noise ratio. Traditional location approaches rely on automated picking, based on individual seismograms, and make no use of the coherency information between signals at different stations. This strong limitation has been overcome by full-waveform location methods, which exploit the coherency of waveforms at different stations and improve the location robustness even in presence of noise. However, the performance of these methods strongly depend on the accuracy of the adopted velocity model, which is often quite rough; inaccurate models result in large location errors. We present an improved waveform stacking location method based on source-specific station corrections. Our method inherits the advantages of full-waveform location methods while strongly mitigating the dependency on the accuracy of the velocity model. With this approach the influence of an inaccurate velocity model on the results is restricted to the estimation of travel times solely within the seismogenic volume, but not for the entire source-receiver path. We finally successfully applied our new method to a realistic synthetic dataset as well as real data.

How wide is the ocular spectrum of Delleman syndrome?

We describe a patient with cerebral and cutaneous features typical of oculocerebrocutaneous syndrome. The ocular anomalies observed have not been previously reported in patients affected with this syndrome.

A prospective observational study of associated anomalies in Hirschsprung's disease.

BACKGROUND: Associated anomalies have been reported in around 20% of Hirschsprung patients but many Authors suggested a measure of underestimation. We therefore implemented a prospective observational study on 106 consecutive HSCR patients aimed at defining the percentage of associated anomalies and implementing a personalized and up-to-date diagnostic algorithm. METHODS: After Institutional Ethical Committee approval, 106 consecutive Hirschsprung patients admitted to our Institution between January 2010 and December 2012 were included. All families were asked to sign a specific Informed Consent form and in case of acceptance each patient underwent an advanced diagnostic algorithm, including renal ultrasound scan (US), cardiologic assessment with cardiac US, cerebral US, audiometry, ENT and ophthalmologic assessments plus further specialist evaluations based on specific clinical features. RESULTS: Male to female ratio of our series of patients was 3,4:1. Aganglionosis was confined to the rectosigmoid colon (classic forms) in 74,5% of cases. We detected 112 associated anomalies in 61 (57,5%) patients. The percentage did not significantly differ according to gender or length of aganglionosis. Overall, 43,4% of patients complained ophthalmologic issues (mostly refraction anomalies), 9,4% visual impairment, 20,7% congenital anomalies of the kidney and urinary tract, 4,7% congenital heart disease, 4,7% hearing impairment or deafness, 2,3% central nervous system anomalies, 8,5% chromosomal abnormalities or syndromes and 12,3% other associated anomalies. CONCLUSIONS: Our study confirmed the underestimation of certain associated anomalies in Hirschsprung patients, such as hearing impairment and congenital anomalies of the kidney and urinary tract. Subsequently, based on our results we strongly suggest performing renal US and audiometry in all patients. Conversely, ophthalmologic assessment and cerebral and heart US can be performed according to guidelines applied to the general population or in case of patients with suspected clinical features or chromosomal abnormalities. This updated diagnostic algorithm aims at improving overall outcome thanks to better prognostic expectations, prevention strategies and early rehabilitation modalities. The investigation of genetic background of patients with associated anomalies might be the next step to explore this intriguing multifactorial congenital disease.