Evaluation of neurodevelopmental symptoms in 10 cases of neonatal ichthyosis and sclerosing cholangitis syndrome

Abstract

Neonatal ichthyosis and sclerosing cholangitis (NISCH syndrome; MIM607626) is a rare autosomal recessive genodermatosis characterized by the variable association of mild ichthyosis, scalp hypotrichosis and scarring alopecia, sparse eyebrows, enamel abnormalities, and sclerosing cholangitis of neonatal onset. The absence of liver involvement is reported. 1 NISCH syndrome is caused by bi-allelic pathogenic variants in CLDN1, encoding for Claudin-1 tight junction protein.Among the 19 reported cases, neurodevelopmental manifestations have been reported in only one patient. 2,3 We report an additional family with a CLDN1 mutation and neurodevelopmental symptoms and retrospectively reviewed the association of eight previously reported patients with NISCH.

Neonatal ichthyosis–sclerosing cholangitis syndrome: report of a novel mutation and a review of the literature

“…Anomalies of eyebrows and eyelashes have been reported in only 15 of 21 previous cases whereas, the remaining case reports did not mention this sign. Our patient also had sparse eyebrows and eyelashes, so this sign can be speculated as a common sign in NISCH syndrome (Baala et al, 2002;Hadj-Rabia et al, 2004;Shah and Bhatnagar, 2010;Paganelli et al, 2011;Kirchmeier et al, 2014;Youssefian et al, 2017;Nagtzaam et al, 2018;Izurieta Pacheco et al, 2020;Salik et al, 2022). Histopathological findings of skin identified in NISCH syndrome include follicular keratosis, orthokeratosis, acanthosis, parakeratosis, papillomatosis, intracytoplasmic vacuoles in keratinocytes, and granulayer hyperplasia (Baala et al, 2002;Paganelli et al, 2011).…”

Early diagnosis of ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis syndrome: A case report

“…Treatments aim at improving symptoms and survival, and we recommend monitoring patients with ILVASC for liver function, hair and teeth anomalies, intellectual delay, and bilateral uveal synechiae. 2,13 The main source for morbidity in ILVASC is from liver complications that might necessitate a liver transplant. Although there is substantial…”

“…She may also require longitudinal cognitive assessment due to increased risk of neurodevelopmental impairment both at preschool and school ages. 2…”

Mechanisms of paracellular transport of magnesium in intestinal and renal epithelia

“…Biallelic pathogenic variants in CLDN1 cause neonatal ichthyosis and sclerosing cholangitis (OMIM #607626), an extremely rare autosomal recessive genodermatosis. Plasma Mg concentration was not reported in these patients 78–81 . CLDN1‐deficient mice die within 1 day after birth possibly because of excessive skin water loss 82 .…”

“…Plasma Mg concentration was not reported in these patients. [78][79][80][81] CLDN1-deficient mice die within 1 day after birth possibly because of excessive skin water loss. 82 Cldn1 knock-down (KD) mice were also generated, 83 but Mg homeostasis has not been studied in either model.…”