The IFITM5 Ser40Leu variant can manifest as prenatal Caffey disease.

We report on a female neonate with a clinico-radiological presentation in keeping with a lethal form of prenatal Caffey disease (PCH). She had antenatal and postnatal features of severely bowed long bones, small chest, diaphyseal hyperostosis and polyhydramnios and died shortly after birth. Initial testing excluded COL1A1-related PCH, as an OI gene panel, consisting of COL1A1, COL1A2, CRTAP, and P3H1 genes, was negative. Targeted sequencing using a gene panel was performed and a de novo heterozygous, likely pathogenic variant in IFITM5: c.119C > T(p.Ser40Leu) was identified, which was previously described to cause a severe form of progressively deforming osteogenesis imperfect (OI). To our knowledge, variants in IFITM5 have not been reported in infantile Caffey disease (ICH) or PCH. Given that the pathogenesis of PCH is largely unknown, we postulate that a subset of PCH may be associated with variants in IFITM5.

HIDEA syndrome: A rare cause of congenital hypoventilation in a premature infant.

BACKGROUND: HIDEA (hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy and eye abnormalities) syndrome is a rare and novel disease. We describe a premature patient who required extensive work up for his hypoventilation with a diagnosis of HIDEA syndrome. CASE DESCRIPTION: The patient was born to a pair of consanguineous parents at 32-week gestation. His intermittent bradypnoea requiring significant respiratory support during his postnatal clinical course was atypical for bronchopulmonary dysplasia and this required further extensive work up to look for a cause for his hypoventilation. A trio whole exon sequencing was done which identified homozygous variants in P4HTM, in keeping with the diagnosis of autosomal recessive HIDEA syndrome. He is currently doing well on BiPAP 18 cm H2O / 8 cm H2O, Rate 30 breaths per minute in room air and full nasogastric feeding. He also has cortical blindess and severe global developmental delay. CONCLUSION: Early diagnosis is crucial to optimise adequate ventilatory management including early tracheostomy as many require lifelong continuous or intermittent ventilation. This minimises the complications of chronic hypoxia and reduces mortality risk.

Individual and Area Level Socioeconomic Status and Its Association with Cognitive Function and Cognitive Impairment (Low MMSE) among Community-Dwelling Elderly in Singapore.

BACKGROUND/AIMS: Neighborhood socioeconomic status (SES) can affect cognitive function. We assessed cognitive function and cognitive impairment among community-dwelling elderly in a multi-ethnic urban low-SES Asian neighborhood and compared them with a higher-SES neighborhood. METHODS: The study population involved all residents aged ≥60 years in two housing estates comprising owner-occupied housing (higher SES) and rental flats (low SES) in Singapore in 2012. Cognitive impairment was defined as <24 on the Mini Mental State Examination. Demographic/clinical details were collected via questionnaire. Multilevel linear regression was used to evaluate factors associated with cognitive function, while multilevel logistic regression determined predictors of cognitive impairment. RESULTS: Participation was 61.4% (558/909). Cognitive impairment was found in 26.2% (104/397) of residents in the low-SES community and in 16.1% (26/161) of residents in the higher-SES community. After adjusting for other sociodemographic variables, living in a low-SES community was independently associated with poorer cognitive function (ß = -1.41, SD = 0.58, p < 0.01) and cognitive impairment (adjusted odds ratio 5.13, 95% CI 1.98-13.34). Among cognitively impaired elderly in the low-SES community, 96.2% (100/104) were newly detected. CONCLUSION: Living in a low-SES community is independently associated with cognitive impairment in an urban Asian society.