Novel blended SNRPE-related spliceosomopathy phenotype characterized by microcephaly and congenital atrichia.

Variants in genes encoding core components of the spliceosomes are associated with craniofacial syndromes, collectively called craniofacial spliceosomopathies. SNRPE encodes a core component of pre-mRNA processing U-rich small nuclear ribonuclear proteins (UsnRNPs). Heterozygous variants in SNRPE have been reported in six families with isolated hypotrichosis simplex in addition to one case of isolated non syndromic congenital microcephaly. Here, we report a patient with a novel blended phenotype of microcephaly and congenital atrichia with multiple congenital anomalies due to a de novo intronic SNRPE deletion, c.82-28_82-16del, which results in exon skipping. As discussed within, this phenotype, which we propose be named SNRPE-related syndromic microcephaly and hypotrichosis, overlaps other craniofacial splicesosomopathies.

Correction to: Incidental diagnosis of tuberous sclerosis complex by exome sequencing in three families with subclinical findings.

The published online version contain mistake in the author list. Instead of "A.M.Ilyas" it should have been "M.Ilyas ".

Incidental diagnosis of tuberous sclerosis complex by exome sequencing in three families with subclinical findings.

Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous disorder characterized by lesions and benign tumors in multiple organ systems including the brain, skin, heart, eyes, kidneys, and lungs. The phenotype is highly variable, although penetrance is reportedly complete. We report the molecular diagnosis of TSC in individuals exhibiting extreme intra-familial variability, including the incidental diagnosis of asymptomatic family members. Exome sequencing was performed in three families, with probands referred for epilepsy, autism, and absent speech (Family 1); epileptic spasms (Family 2); and connective tissue disorders (Family 3.) Pathogenic variants in TSC1 or TSC2 were identified in nine individuals, including relatives with limited or no medical concerns at the time of testing. Of the nine individuals reported here, six had post-diagnosis examinations and three met clinical diagnostic criteria for TSC. One did not meet clinical criteria for a possible or definite diagnosis of TSC, and two had only a possible clinical diagnosis following post-diagnosis workup. These individuals as well as their mothers demonstrated limited features that would not raise concern for TSC in the absence of molecular results. In addition, three individuals exhibited epilepsy with normal brain MRIs, and two without seizures or intellectual disability had MRI findings fulfilling major criteria for TSC highlighting the difficulty providers face when relying on clinical criteria to guide genetic testing. Given the importance of a timely TSC diagnosis for clinical management, such cases demonstrate a potential benefit for clinical criteria to include seizures and an unbiased molecular approach to genetic testing.

A prospective study of PHACE syndrome in infantile hemangiomas: demographic features, clinical findings, and complications.

PHACE (OMIM no. 606519) is a neurocutaneous syndrome that refers to the association of large, plaque-like, "segmental" hemangiomas of the face, with one or more of the following anomalies: posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies, and ventral developmental defects, specifically sternal defects and/or supraumbilical raphe. The etiology and pathogenesis of PHACE is unknown, and potential risk factors for the syndrome have not been systematically studied. The purpose of this study was thus to determine (1) the incidence of PHACE and associated anomalies among a large cohort of hemangioma patients, (2) whether certain demographic, prenatal or perinatal risk factors predispose infants to this syndrome, and (3) whether the cutaneous distribution of the hemangioma can be correlated to the types of anomalies present. We undertook a prospective, cohort study of 1,096 children with hemangiomas, 25 of whom met criteria for PHACE. These 25 patients represented 20% of infants with segmental facial hemangiomas. Compared to previous reports, our PHACE patients had a higher incidence of cerebrovascular and cardiovascular anomalies. Two developed acute arterial ischemic stroke during infancy, while two with cardiovascular anomalies showed documented evidence of normalization, suggesting that both progressive and regressive vascular phenomena may occur in this syndrome. Correlation to the anatomic location of the hemangioma appears to be helpful in determining which structural abnormalities might be present. A comparison of demographic and perinatal data between our PHACE cases and the hemangioma cohort overall showed no major differences, except a trend for PHACE infants to be of slighter higher gestational age and born to slightly older mothers. Eighty-eight percent were female, a finding which has been noted in multiple other reports. Further research is needed to determine possible etiologies, optimal evaluation, and outcomes.

Topical ointment therapy benefits premature infants.

OBJECTIVE: Premature infants have an ineffective epidermal barrier. The aim of this study was to investigate the cutaneous and systemic effects of preservative-free topical ointment therapy in premature infants. STUDY DESIGN: We conducted a prospective, randomized study of 60 infants less than 33 weeks' estimated gestational age. The treated infants received therapy for 2 weeks with twice-daily preservative-free topical ointment therapy while the control group received no topical treatment or as-needed therapy with a water-in-oil emollient. Data collection included transepidermal water loss (TEWL) measurement, skin condition evaluations, fungal and quantitative bacterial skin cultures, analysis of fluid requirements, patterns of weight low or gain, and the incidence of blood and cerebrospinal fluid cultures positive for microorganisms. RESULTS: We found that topical ointment therapy significantly decreased TEWL during the first 6 hours after the initial application. TEWL was decreased by 67% (p = 0.0001) when measured 30 minutes after application and 34% (p = 0.001) when measured 4 to 6 hours after application. We also observed significantly superior skin condition scores in the treated group on study days 7 and 14 (p = 0.001) and 0.0004, respectively). Quantitative bacterial cultures revealed significantly less colonization of the axilla on day 2, 3, or 4 and on day 14 (p = 0.008 and 0.04, respectively). The incidence of positive findings in blood and/or cerebrospinal fluid cultures was 3.3% in the treated group of infants versus 26.7% in the control group (p = 0.02). There was no statistical difference in the fluid requirements or patterns of weight gain or loss during the 2 weeks of the study. CONCLUSIONS: Preservative-free topical ointment therapy decreased TEWL for 6 hours after application, decreased the severity of dermatitis, and decreased bacterial colonization of axillary skin. Infants treated with ointment had fewer blood and cerebrospinal fluid cultures positive for microorganisms. These data support the use of topical ointment therapy in very premature infants during the first weeks after birth.