Ichthyosis is a clinically and genetically heterogeneous group of disorders of keratinization characterized by a significant and incapacitating scaling of the skin. Most forms are congenital and display different modes of inheritance. Two major forms have been described clinically: (1) the primary forms, in which the disorder is largely limited to the skin, and (2) the ichthyosiform syndromes, in which ichthyosis is a part of a multisystem disorder. In the first group, two major forms have been defined, lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE).
Nonbullous congenital ichthyosiform erythroderma is an inflammatory form of ichthyosis with an estimated frequency of 1/300,000 and is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. At birth, 90 % of the affected individuals present as collodion babies. Palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume are also present in affected patients. In 50 % of the cases, a nail dystrophy including ridging, subungeal hyperkeratosis, or hypoplasia has been described. Ectropion, eclabion, scalp involvement, and loss of eyebrows and lashes are also seen. Histologic features include hyperkeratosis, an increase in stratum corneum thickness, a normal or prominent granular layer, and increased mitoses point to a hyperproliferative epidermal defect.
Mutations in any of the three known causative genes, TGM1, ALOXE3 or ALOX12B, can lead either to NCIE or LI. Transglutaminases, including the product of the TGM1 gene, catalyze formation of epsilon-(gamma-glutamyl)-lysine crosslinks in proteins and thereby stabilize biological structures. In epidermis, TGM1 is required for the formation of the cross-linked envelope. Point mutations in the TGM1 gene cause deficits in enzyme activity.
Lefevre et al. (2004) identified a gene for a new form of non-syndromic autosomal recessive congenital ichthyosis (ARCI) and studied its genomic localization by homozygosity mapping. The study included 11 patients (six males and five females) with ARCI from eight consanguineous Algerian families. Some patients were born as collodion babies. Seven patients presented the nonbullous congenital ichthyosiform erythroderma (NCIE) phenotype. Those patients had generalized ichthyosis with erythema, fine whitish scaling on the face and trunk, and larger brownish scaling on the neck, buttocks and legs. NCIE patients revealed hyperkeratosis, thickening of the stratum corneum and moderate acanthosis and parakeratosis. All patients had palmoplanter keratoderma, often yellowish with fissures, and some had clubbing of nails.
Shawky et al. (2004) investigated forty-three autosomal recessive congenital ichthyosis (ARCI) Egyptian individuals in 16 families with severe lamellar ichthyosis (LI) and 10 families with congenital ichthyosiformis erythroderma (CIE). Shawky et al. (2004) identified 5 alleles in two Egyptian families as having intron-5/exon-6 splice acceptor mutation recognized by the MspI restriction endonuclease. This promoted to a frequency of 9.6% for this mutation (5 splice-mutation alleles/52 alleles tested). Shawky et al. (2004) extended their dataset to update the detection of R142H mutation in 4 CIE Egyptian families and one LI phenotype (frequency of 28.8%; 15/52). However, they did not observe the R141H among the Egyptian population. There was also no correlation between phenotype and genotype in the study. The mutant alleles detected in intron-5 acceptor splice-site were associated with the other extreme of CIE phenotypes rather than the severe LI form.
Al-Zayir and Al-Amro (2006) conducted a study between January 1990 and December 1995 in King Fahad hospital of the University, Saudi Arabia to document the clinical and epidemiological features of patients with primary hereditary ichthyosis (PHI). Out of 10455 dermatology patients; a total of 71 patients (44 males and 27 females) were diagnosed with PHI. Consanguinity among the parents of the patients was significantly high (85%); parents of 60 of the 71 patients were married to either first-degree relatives or to second-degree relatives. Fifty-three of the 71 patients had positive family history of PHI. Nonbullous Ichthyosiform Erythroderma was diagnosed in 29.6% of these patients.
Bastaki et al. (2017) conducted a study to identify the underlying gene mutations in Emirati congenital ichthyosis patients. A female patient, born as a collodion baby with MRSA sepsis and bilateral pneumonia, was described. She exhibited generalized thick dry skin with ichthyosis on the soles, but by age 10 months her skin condition greatly improved. She also had abnormal palmar creases, camptodactyly of the fifth fingers, Mongolian spot on the buttocks, cutis marmorata and dysmorphic features such as a broad forehead, a depressed broad nasal bridge, micrognathia, and malformed ears with thick helices. She was diagnosed with nonbullous CIE and WES uncovered a homozygous c.944T>C (p.Leu315Pro) mutation in exon 8 of the ALOX12B gene. The mutation was predicted to be functionally damaging and the patient’s consanguineous parents were both found to be heterozygous carriers.
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