Fatal neonatal nephrocutaneous syndrome in 18 Roma children with EGFR deficiency.

Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with tyrosine-kinase signaling activity, involved in many cellular functions including cell growth and differentiation. Germ line loss-of-function mutations in EGFR lead to a severe neonatal skin disorder (Online Mendelian Inheritance in Man #131550). We report 18 premature Roma children from 16 families with birthweights ranging 440-1470 g and multisystem diseases due to the homozygous mutation c.1283G˃A (p.Gly428Asp) in EGFR. They presented with thin, translucent, fragile skin (14/15), skin desquamation (10/17), ichthyosis (9/17), recurrent skin infections and sepsis (9/12), nephromegaly (10/16) and congenital heart defects (7/17). Their prognosis was poor, and all died before the age of 6 months except one 13-year-old boy with a severe skin disorder, dentinogenesis imperfecta, Fanconi-like syndrome and secondary hyperaldosteronism. Management of ion and water imbalances and extremely demanding skin care may improve the unfavorable outcome of such patients.

Clinical, molecular, and pathological findings in a Neu-Laxova syndrome stillborn: A Brazilian case report.

Neu-Laxova syndrome (NLS) is a lethal genetic multiple congenital anomaly syndrome of unknown prevalence representing the severe spectrum of serine biosynthesis defects associated with PHGDH, PSAT1, or PSP gene mutations. The purpose of this study was to describe clinical/molecular and pathologic features of a NLS case caused by novel heterozygous missense variant in PHGDH gene identified in his consanguineous parents.

Updated strategies for the management, pathogenesis and molecular genetics of different forms of ichthyosis syndromes with prominent hair abnormalities.

Syndromic ichthyosis is rare inherited disorders of cornification with varied disease complications. This disorder appears in seventeen subtypes associated with severe systematic manifestations along with medical, cosmetic and social problems. Syndromic ichthyosis with prominent hair abnormalities covers five major subtypes: Netherton syndrome, trichothiodystrophy, ichthyosis hypotrichosis syndrome, ichthyosis hypotrichosis sclerosing cholangitis and ichthyosis follicularis atrichia photophobia syndrome. These syndromes mostly prevail in high consanguinity states, with distinctive clinical features. The known pathogenic molecules involved in ichthyosis syndromes with prominent hair abnormalities include SPINK5, ERCC2, ERCC3, GTF2H5, MPLKIP, ST14, CLDN1 and MBTPS2. Despite underlying genetic origin, most of the health professionals solely rely on phenotypic expression of these disorders that leads to improper management of patients, hence making these patients living an orphanage life. After dermal features, association of other systems such as nervous system, skeletal system, hair abnormalities or liver problems may sometimes give clues for diagnosis but still leaving place for molecular screening for efficient diagnosis. In this paper, we have presented a review of ichthyosis syndrome with prominent hair abnormalities, with special emphasis on their updated genetic consequences and disease management. Additionally, we aim to update health professionals about the practice of molecular screening in ichthyosis syndromes for appropriate diagnosis and treatment.

An absence of nuclear lamins in keratinocytes leads to ichthyosis, defective epidermal barrier function, and intrusion of nuclear membranes and endoplasmic reticulum into the nuclear chromatin.

B-type lamins (lamins B1 and B2) have been considered to be essential for many crucial functions in the cell nucleus (e.g., DNA replication and mitotic spindle formation). However, this view has been challenged by the observation that an absence of both B-type lamins in keratinocytes had no effect on cell proliferation or the development of skin and hair. The latter findings raised the possibility that the functions of B-type lamins are subserved by lamins A and C. To explore that idea, we created mice lacking all nuclear lamins in keratinocytes. Those mice developed ichthyosis and a skin barrier defect, which led to death from dehydration within a few days after birth. Microscopy of nuclear-lamin-deficient skin revealed hyperkeratosis and a disordered stratum corneum with an accumulation of neutral lipid droplets; however, BrdU incorporation into keratinocytes was normal. Skin grafting experiments confirmed the stratum corneum abnormalities and normal BrdU uptake. Interestingly, the absence of nuclear lamins in keratinocytes resulted in an interspersion of nuclear/endoplasmic reticulum membranes with the chromatin. Thus, a key function of the nuclear lamina is to serve as a "fence" and prevent the incursion of cytoplasmic organelles into the nuclear chromatin.

Prenatal sonographic assessment and perinatal course of ichthyosis prematurity syndrome.

All cases of ichthyosis prematurity syndrome (IPS), registered at the National Center for Fetal Medicine in Trondheim, Norway between 1987 and 2010 were identified and the findings analyzed. Five fetuses with IPS were identified between 1988 and 2000. All five developed polyhydramnios between 28 and 31 weeks. The fetal stomach appeared to be empty in four cases, and was not described in one case. The fetal skin was described as 'uneven' at ultrasound examination in two cases. Separation of chorionic and amniotic membranes with a peculiar appearance of echo-free fluid in the chorionic cavity and echogenic sediment in the amniotic cavity were observed between 28 + 5 and 32 + 3 weeks in all cases. All fetuses were delivered prematurely between 30 and 34 weeks. All neonates had difficulties in breathing, two developed aspiration pneumonia, and one had bilateral pneumothorax after intubation and died at 6 months because of pulmonary and cardiac sequelae. Prenatal sonographic signs of IPS are separation of the membranes, echogenic amniotic fluid and echo-free chorionic fluid occurring between 28 and 32 weeks' gestation. Delivery occurs at 30-34 weeks and, as there is a high risk of asphyxia, an experienced neonatal intensive care unit team should be present at delivery.