Lamellar ichthyosis (ORPHA:313)
A rare autosomal recessive congenital ichthyosis characterized by the presence of large scales all over the body without significant erythroderma.
Epidemiology
It is the most common variant of autosomal recessive congenital ichthyosis (ARCI). Prevalence in Europe is estimated at approximately 1/100,000-1/300,000 individuals.
Clinical description
Newborns are often encased in a collodion membrane (taut, shiny, translucent membrane appearing as an extra skin layer) with ectropion and eclabium. Once the membrane has been shed (after one to two weeks), scales covering the whole body become apparent. In classic lamellar ichthyosis (LI), scales are large, dark and plate-like. Milder forms with lighter and thinner scales are possible. Contrarily to congenital ichthyosiform erythroderma (CIE), there is no significant erythroderma. Nevertheless, LI and CIE are the two extremities of the same spectrum, with many patients exhibiting intermediate phenotypes. Furthermore, patients' phenotypes may change over time or under treatment. Skin is usually itchy or painful (with cracks), mobility can be reduced due to skin stiffness over the joints, and cutaneous barrier function is impaired, which can result in increased transepidermal water loss and a proneness to dehydration. Other associated features include: persistent ectropion and associated eye complications (keratitis, corneal scarring), nail dystrophy, scarring alopecia, palmoplantar keratoderma, failure to thrive, short stature, hypohidrosis with heat intolerance, and impaired hearing (due to the accumulation of scales in the external ear).
Etiology
LI is a genetically heterogeneous disease within the disease spectrum of autosomal recessive congenital ichthyosis (ARCI) generally due to mutations in the genes TGM1, ABCA12, ALOX12B, and NIPAL4. Most mutations are found in the TGM1 gene encoding transglutaminase 1, involved in the formation of the epidermal cornified cell envelope. ABCA12 encodes an ATP-binding cassette (ABC) transporter, involved in lipid transport, ALOX12B and NIPAL4 encode arachidonate 12(R)-lipoxygenase and ichthyn respectively and are involved in lipid metabolism. There is no clear genotype-phenotype correlation. There also exists an autosomal dominant lamellar ichthyosis with palmoplantar keratoderma due to mutations in ASPRV1, which encodes a protease involved in Filaggrin processing.
Diagnostic methods
The diagnosis is based on the clinical appearance of the skin and can be confirmed by genetic testing. Histological features include orthohyperkeratosis, a normal to slightly widened stratum granulosum, acanthosis, and papillomatosis of the epidermis. Immunohistochemistry using antibodies directed against transglutaminase 1 or transglutaminase 1 enzyme activity measurement is available in some centers. Molecular testing (such as gene panel diagnosis) is possible in national reference laboratories.
Differential diagnosis
Differential diagnosis includes syndromic forms of ichthyosis, recessive X-linked ichthyosis and semidominant ichthyosis vulgaris, and CIE in case of erythroderma.
Antenatal diagnosis
Prenatal diagnosis is based on DNA analysis of amniocentesis and chorion villus sampling materials.
Genetic counseling
Genetic counseling should be offered to the affected families.
Management and treatment
Newborns presenting with collodion baby are usually admitted to a neonatal intensive care unit for 2 to 4 weeks. In later life, management is based on daily applications of emollients and/or keratolytics. Oral retinoids are useful in severe forms. Acitretin is the only retinoid approved by the European Medical Agency (EMA). Usually dosages of 0.5 mg/kg/day are sufficient. Doses should be maintained as low as 10-25 mg/day.
Prognosis
Prognosis is variable. During the neonatal period, there is a risk of sepsis and electrolyte imbalance. The disease often remains stable throughout life, with periods of exacerbation. Life expectancy is normal after the somewhat critical neonatal period. LI has a strong impact on quality of life due to altered physical appearance, troublesome symptoms, and the many constraints due to the disease and its treatment.

                            Last update: 
                            December 2022


                            - Expert reviewer(s): 
                            Dr Kira SÜßMUTH | ERN-Skin*


                                * European Reference Network