IllnessIchthyosis, congenital, recessive; differential diagnosis

NGS +

Autosomal recessive congenital ichthyosis (ARKI) is a heterogeneous group of keratinization disorders mainly associated with abnormal skin scaling all over the body. ARKI is confined to the skin, with >60% of patients presenting with severe symptoms. The main phenotypes are lamellar ichthyosis and nonbullous congenital ichthyosiform erythroderma (NCIE); phenotypic overlap may occur. Neither histopathologic nor ultrastructural features clearly distinguish between the two forms, and mutations in multiple genes cause both lamellar and NCIE phenotypes. NCIE is characterized by marked erythroderma and fine white scales. Most patients have a collodion membrane perinatally and show palmoplantar keratoderma. Nail dystrophy is observed in 50% of cases. In lamellar ichthyosis, the scales are large and pigmented without skin redness. The overlapping phenotypes depend on the age of the patient and the body region. Terminal differentiation of the epidermis is disturbed in both forms. Harlequin ichthyosis represents a 3.rd most severe and often fatal phenotype. Later in life, ARCI skin may show scales covering the entire body, and erythema may be very mild. Some affected individuals exhibit scarring alopecia, and many show secondary anhidrosis. With a comprehensive panel that includes guideline genes as well as others, the diagnostic yield can be as high as 80% or more, depending on prior clinical characterization. However, a negative DNA result does not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1420/

• Allelic: Bart-Pumphrey syndrome (GJB2)
• Allelic: Chondrodysplasia punctata, XLD (EBP)
• Allelic: Deafness, AD 3A (GJB2)
• Allelic: Deafness, AD 3B (GJB6)
• Allelic: Deafness, AR 1A (GJB2)
• Allelic: Deafness, AR 1B (GJB6)
• Allelic: Deafness, digenic GJB2/GJB6 (GJB6)
• Allelic: Dermatitis, atopic, susceptibility to, 2 (FLG)
• Allelic: Hair morphology 1, hair thickness (EDAR)
• Allelic: Lewy body dementia, susceptibility to (GBA)
• Allelic: Parkinson disease, late-onset, susceptibility to (GBA)
• Allelic: Tooth agenesis, selective, 4 (WNT10A)
• Allelic: Tooth agenesis, selective, XL 1 (EDA)
• Allelic: Xeroderma pigmentosum, group B (ERCC3)
• Chanarin-Dorfman syndrome, nonbullous congenital ichthyosiform erythroderma (ABHD5)
• Ectodermal dysplasia 1, hypohidrotic, XL (EDA)
• Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, AD (EDAR)
• Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, AR (EDAR)
• Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, AD (EDARADD)
• Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, AR (EDAEADD)
• Ectodermal dysplasia 2, Clouston type (GJB6)
• Epidermolytic hyperkeratosis (KRT1)
• Epidermolytic hyperkeratosis (KRT10)
• Gaucher disease, perinatal lethal (GBA)
• Gaucher disease, type I, II, III, IIIC (GBA)
• Hystrix-like ichthyosis with deafness (GJB2)
• Ichthyosis bullosa of Siemens (KRT2)
• Ichthyosis histrix, Curth-Macklin type (KRT1)
• Ichthyosis prematurity syndrome (SLC27A4)
• Ichthyosis vulgaris (FLG)
• Ichthyosis with confetti (KRT10)
• Ichthyosis, XL (STS)
• Ichthyosis, congenital, AR 1 (TGM1)
• Ichthyosis, congenital, AR 10 (PNPLA1)
• Ichthyosis, congenital, AR 11 (ST14)
• Ichthyosis, congenital, AR 12 (CASP14)
• Ichthyosis, congenital, AR 13 (SDR9C7)
• Ichthyosis, congenital, AR 14 (SULT2B1)
• Ichthyosis, congenital, AR 2 (ALOX12B)
• Ichthyosis, congenital, AR 3 (ALOXE3)
• Ichthyosis, congenital, AR 4A, 4B [harlequin] (ABCA12)
• Ichthyosis, congenital, AR 5 (CYP4F22)
• Ichthyosis, congenital, AR 6 (NIPAL4)
• Ichthyosis, congenital, AR 8 (LIPN)
• Ichthyosis, congenital, AR 9 (CERS3)
• Ichthyosis, cyclic, with epidermolytic hyperkeratosis (KRT1)
• Ichthyosis, cyclic, with epidermolytic hyperkeratosis (KRT10)
• Keratitis-ichthyosis-deafness syndrome (GJB2)
• Keratoderma, palmoplantar, with deafness (GJB2)
• Keratosis palmoplantaris striata III (KRT1)
• MEND syndrome: Male EBP disorder + Neurologic Defects (EBP)
• Netherton syndrome: congenital erythroderma, ichthyosiform, hypotrichosis, hyper-IgE (SPINK5)
• Odontoonychodermal dysplasia (WNT10A)
• Palmoplantar keratoderma, epidermolytic (KRT1)
• Palmoplantar keratoderma, nonepidermolytic (KRT1)
• Schopf-Schulz-Passarge syndrome: eccrine tumors + ectodermal dysplasia (WNT10A)
• Sjogren-Larsson s.: ichthyosis, MR, spastic paraparesis, macular dystr., leukoencephalop- (ALDH3A2)
• Trichothiodystrophy 2, photosensitive (ERCC3)
• Trichothiodystrophy 3, photosensitive (GTF2H5)
• Trichothiodystrophy 4, nonphotosensitive (MPLKIP)
• Trichothiodystrophy 5, nonphotosensitive (RNF113A)
• Trichothiodystrophy 6, nonphotosensitive (GTF2E2)
• Vohwinkel syndrome (GJB2)