IllnessIchthyosis + related dyskeratinoses, differential diagnosis

NGS +

[[Sanger]]

Ichthyoses are generalized dermatoses characterized by varying degrees of scaling, hyperkeratosis as well as erythroderma. They are often associated with palmoplantar keratoderma (PPK) or hyperlinearity. These keratinization disorders may be genetic or acquired. Hereditary ichthyosis is divided into syndromal and non-syndromal forms. In congenital ichthyoses, skin symptoms present either as collodion membrane or congenital ichthyosiform erythroderma. Collodion babies later develop lamellar ichthyosis or rarer variants such as improving collodion ichthyosis. The latter includes the rare autosomal recessive congenital ichthyosis, which manifests clinically as, for example, harlequin ichthyosis. In the common ichthyoses such as ichthyosis vulgaris, skin symptoms usually do not appear until several weeks to months after birth. Ichthyoses caused by keratin mutations, such as epidermolytic ichthyosis, superficial epidermolytic ichthyosis and congenital reticular ichthyosiform erythroderma, are called keratinopathic ichthyoses. They often manifest with blistering at birth. The PPKs also include a heterogeneous group of disorders characterized by persistent epidermal thickening of the palms and soles, such as diffuse hereditary PPK, focal and striatal hereditary PPK, and punctate hereditary PPK. In these two large groups of cornification disorders, all classical inheritance patterns are observed. The DNA diagnostic yield appears to be between 50-80%, largely depending on the given clinical workup of the patient group. Therefore, a negative result does not exclude the clinical dermatological diagnosis.

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

https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3432

https://www.ncbi.nlm.nih.gov/books/NBK562318/

https://emedicine.medscape.com/article/1108406-overview

• Allelic: CK syndrome (NSDHL)
• Allelic: Cardiomyopathy, dilated, with woolly hair + keratoderma (DSP)
• Allelic: Chondrodysplasia punctata, XLD (EBP)
• Allelic: Dilated cardiomyopathy with woolly hair, keratoderma + tooth agenesis (DSP)
• Allelic: Peeling skin syndrome 1 (CDSN)
• Allelic: Proteasome-associated autoinflammatory syndrome 2 (POMP)
• Allelic: Psoriasis 2 (CARD14)
• Allelic: Spinocerebellar ataxia 34 (ELOVL4)
• Allelic: Stargardt disease 3 (ELOVL4)
• Allelic: Xeroderma pigmentosum, group B (ERCC3)
• Allelic: Xeroderma pigmentosum, group D (ERCC2)
• Adermatoglyphia (SMARCAD1)
• Allelic: Lewy body dementia, susceptibility to (GBA)
• Allelic: Parkinson disease, late-onset, susceptibility to (GBA)
• Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratod. + woolly hair (DSC2)
• Arthrogryposis, renal dysfunction + cholestasis 1 (VPS33B)
• Basan syndrome (SMARCAD1)
• CHILD syndrome (NSDHL)
• CHIME syndrome (PIGL)
• Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (SNAP29)
• Chanarin-Dorfman syndrome (ABHHD5)
• Cole disease (ENPP)
• Dermatopathia pigmentosa reticularis (KRT14)
• Ectodermal dysplasia 2, Clouston type (GJB6)
• Epidermolysis bullosa simplex, Dowling-Meara type (KRT14)
• Epidermolysis bullosa simplex, Koebner type (KRT14)
• Epidermolysis bullosa simplex, Weber-Cockayne type (KRT14)
• Epidermolysis bullosa simplex, recessive 1 (KRT14)
• Epidermolysis bullosa, lethal acantholytic (DSP)
• Epidermolytic hyperkeratosis (KRT1)
• Epidermolytic hyperkeratosis (KRT10)
• Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis + hyper IgE (DSG1)
• Erythrokeratodermia variabilis et progressiva 1 (GJB3)
• Erythrokeratodermia variabilis et progressiva 2 (GJB4)
• Erythrokeratodermia variabilis et progressiva 3 (GJA1)
• Erythrokeratodermia variabilis et progressiva 4 (KDSR)
• Gaucher disease, perinatal lethal (GBA)
• Gaucher disease, type I, II, III, IIIC (GBA)
• Huriez syndrome (SMARCAD1)
• IFAP syndrome with or without BRESHECK syndrome (MBTPS2)
• 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 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, congenital, Ar 13 (SDR9C7)
• Ichthyosis, cyclic, with epidermolytic hyperkeratosis (KRT1)
• Ichthyosis, cyclic, with epidermolytic hyperkeratosis (KRT10)
• Ichthyosis, lamellar, AD (ASPRV1)
• Ichthyosis, leukocyte vacuoles, alopecia + sclerosing cholangitis (CLDN1)
• Ichthyosis, spastic quadriplegia + mental retardation (ELOVL4)
• Ichthyotic keratoderma, spasticity, hypomyelination + dysmorphic facies (ELOVL1)
• Keratitis-ichthyosis-deafness syndrome (GJB2)
• Keratoderma, palmoplantar, punctate type IA (AAGAB)
• Keratoderma, palmoplantar, with deafness (GJB2)
• Keratosis follicularis spinulosa decalvans, XL (MBTPS2)
• Keratosis linearis with ichthyosis congenita + sclerosing keratoderma (POMP)
• Keratosis palmoplantaris striata I, AD (DSG1)
• Keratosis palmoplantaris striata II (DSP)
• Keratosis palmoplantaris striata III (KRT1)
• MEDNIK syndrome (AP1S1)
• MEND syndrome (EBP)
• Meleda disease (SLURP1)
• Microcephaly, congenital cataract + psoriasiform dermatitis (MSMO1)
• Multiple sulfatase deficiency (SUMF1)
• Naegeli-Franceschetti-Jadassohn syndrome (KRT14)
• Naxos disease (JUP)
• Netherton syndrome (SPINK5)
• Olmsted syndrome 1 (TRPV3)
• Olmsted syndrome, XL (MBTPS2)
• Pachyonychia congenita 1 (KRT16)
• Pachyonychia congenita 2 (KRT17)
• Pachyonychia congenita 3 (KRT6A)
• Pachyonychia congenita 4 (KRT6B)
• Palmoplantar hyperkeratosis and true hermaphroditism (RSPO1)
• Palmoplantar hyperkeratosis with squamous cell carcinoma of skin + sex reversal (RSPO1)
• Palmoplantar keratoderma with congenital alopecia (GJA1)
• Palmoplantar keratoderma, Bothnian type (AQP5)
• Palmoplantar keratoderma, Nagashima type (SERPINB7)
• Palmoplantar keratoderma, epidermolytic (KRT1)
• Palmoplantar keratoderma, epidermolytic (KRT9)
• Palmoplantar keratoderma, nonepidermolytic (KRT1)
• Palmoplantar keratoderma, nonepidermolytic, focal (KRT16)
• Palmoplantar keratoderma, nonepidermolytic, focal 2 (TRPV3)
• Palmoplantar keratoderma, nonepidermolytic, focal or diffuse (KRT6C)
• Peeling skin syndrome 2 (TGM5)
• Peeling skin syndrome 3 (CHST8)
• Peeling skin syndrome 4 (CSTA)
• Peeling skin syndrome 6 (FLG2)
• Peeling skin with leukonychia, acral punctate keratoses, cheilitis + knuckle pads (CAST)
• Pityriasis rubra pilaris (CARD14)
• Refsum disease (PHYH)
• Sjogren-Larsson syndrome (ALH3A2)
• Skin fragility-woolly hair syndrome (DSP)
• Steatocystoma multiplex (KRT17)
• Trichothiodystrophy 1, photosensitive (ERCC2)
• Trichothiodystrophy 2, photosensitive (ERCC3)
• Trichothiodystrophy 3, photosensitive (GTF2H5)
• Trichothiodystrophy 4, nonphotosensitive (MPLKIP)
• Trichothiodystrophy 5, nonphotosensitive (RNF113A)
• Trichothiodystrophy 6, nonphotosensitive (GTF2E2)
• Tylosis with esophageal cancer (RHBDF2)
• Tyrosinemia, type II (TAT)
• Vohwinkel syndrome with ichthyosis (LORICRIN)
• Weill-Marchesani 4 syndrome, AR (ADAMTS17)