NORD gratefully acknowledges Peri L. Cavusgil, MSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.
Summary
Lamellar ichthyosis (LI) is a rare genetic skin disorder that is present at birth. It is one of three genetic skin disorders called autosomal recessive congenital ichthyoses (ARCI). The other two are known as harlequin ichthyosis and congenital ichthyosiform erythroderma. All ARCI conditions are considered a clinical spectrum. There is overlap in symptoms between ARCI conditions. In LI, the body creates skin cells at a normal rate. However, they do not separate from each other at the surface of the skin the way they should. In addition, the body does not shed the skin fast enough, causing brown scales to form.
Babies born with LI are sometimes called “collodion babies.” They are covered in a clear membrane (collodion) so it looks like they are covered with plastic wrap. Their skin can look red or dark, tight, and split. These newborns can have skin that is so tight that it forces their lips to turn outward. Also, the skin on their hands may be tight, preventing them from extending their fingers. Newborns can have problems regulating their body temperature and preventing water loss. They may also be more likely to develop skin infections. The collodion membrane is usually shed a few days to a few weeks after birth. Once this happens, the newborn is covered with broad, dark scales. The space in between the scales may be shallow or deep.
Some people with LI cannot close their eyes because the skin is so tight. In some cases, the skin around the eyes pulls so tightly that it causes the eyelids to turn outward. It can lead to irritation of the inner eyelid and drying of the eyeball. Some doctors recommend surgery to prevent damage to the eyeball and vision problems. People with LI may also have thick nails and hair loss due to the thickness of the scales on their scalp. They may also have thick skin on the palms of the hands and soles of the feet.
LI can be caused by harmful changes in several genes. The most common gene related to this condition is TGM1. Other genes include NIPAL4, ALOX12B, and CYP4F22. These genes provide the instructions to make enzymes and proteins. These enzymes and proteins are important for normal development, function, and shedding of skin cells. There is also evidence that more genes are related to LI. The severity of the condition cannot always be determined based on genetic testing results.
The harmful changes that cause LI are recessively inherited. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and therefore have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
LI occurs in about one in 200,000 people. The condition can affect people of all genders, races, and ethnicities.
Treatment
LI is usually treated topically. Doctors use creams that help repair the skin barrier. These creams often contain ceramides or cholesterol. Moisturizers with petrolatum or lanolin may also be used. Sometimes, mild keratolytics or topical retinoids are used as treatment options. Doctors may treat severe LI with oral retinoids. Retinoids can be toxic to the body, so they are used with caution.
To diagnose and treat ARCI, including LI, people may need to see the following medical specialists:
Tests for temperature regulation problems and water loss as well as tests for infection may be needed.
Most current treatments do not address skin inflammation that some people with LI have. Researchers are exploring the use of anti-inflammatory medications used to treat psoriasis (a different type of skin condition) for those with LI. Researchers are also trying to personalize treatment to the specific harmful gene change a patient has. This approach could lead to better therapies for people with LI. Lastly, experimental studies are being conducted to determine if enzyme replacement therapy (ERT) could be a treatment option. However, ERT would only be an option for people with certain harmful gene changes.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials are also posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact:
http://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
For information about current research related to ichthyosis, contact the Foundation for Ichthyosis & Related Skin Types listed in the Resources section of this report.
JOURNAL ARTICLES
Vahlquist A, Fischer J, Törmä H. Inherited Nonsyndromic Ichthyoses: An Update on Pathophysiology, Diagnosis and Treatment. Am J Clin Dermatol. 2018;19(1):51-66.
Marukian NV, Choate KA. Recent advances in understanding ichthyosis pathogenesis. F1000Res. 2016;5.
Takeichi T, Akiyama M. Inherited ichthyosis: Non-syndromic forms. The Journal of Dermatology. 2016;43(3):242-251.
Dyer JA, Spraker M, Williams M. Care of the newborn with ichthyosis. Dermatologic Therapy. 2013;26(1):1-15.
Chaurasia S, Das S, Ramamurthy B. Microbial keratitis in a case of lamellar ichthyosis. Int Ophthalmol. 2008;28(5):367-368.
Small K, Ginsburg H, Greco MA, Sarita–Reyes C, Kupchik G, Blei F. More than Skin Deep: A Case of Congenital Lamellar Ichthyosis, Lymphatic Malformation, and Other Abnormalities. Lymphatic Research and Biology. 2008;6(1):39-44.
Kumar TS, Scott XJ, Simon A, Raghupathy P. Vitamin D deficiency rickets with Lamellar ichthyosis. Journal of Postgraduate Medicine. 2007;53(3):215.
DiGiovanna JJ, Robinson-Bostom L. Ichthyosis: Etiology, Diagnosis, and Management. American Journal of Clinical Dermatology. 2003;4(2):81.
Williams ML, Elias PM. Enlightened therapy of the disorders of cornification. Clinics in Dermatology. 2003;21(4):269-273.
Williams ML. Lamellar ichthyosis and Congenital Ichthyosiform Erythroderma (CIE). Ichthyosis Focus. Fall 2003; 22(3): 1-4.
Buxman M, Hickman J, Ragsdale W, Stretcher G, Krochmal L, Wehr RF. Therapeutic activity of lactate 12% lotion in the treatment of ichthyosis: Active versus vehicle and active versus a petrolatum cream. Journal of the American Academy of Dermatology. 1986;15(6):1253-1258.
INTERNET
Richard G. Autosomal Recessive Congenital Ichthyosis. 2001 Jan 10 [Updated 2017 May 18]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1420/ Accessed July 6, 2020.
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