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Diagnosis of X-Linked Recessive Ichthyosis
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Susquehanna University
Affected
I
Normal
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Based on the general symptoms, Psoriasis, Hyperkeratosis lenticularis perstans, and
Ichthyosis were considered to be three possible genetic diseases that the patient’s family members
could be diagnosed with. Psoriasis is an “inflammatory skin disease that affects 2% of the
population” (Matthews, 1996) and is characterized by “red, scaly skin patches.”(Matthews, 1996)
Hyperkeratosis lenticularis perstans, also known as Flegel’s Disease, is an autosomal dominant
disease in which lesions are mostly present on the lower extremities (Beveridge, 1973), however
they may be found all over the body. Hyperkeratosis lenticularis perstans is often associated with
the presence of skin tumors and mostly appears during the third and fourth decades of one’s life.
Ichthyosis is characterized as having large, dark brown scales (Hernandez-Martin, 2005) that are
first present between ages three to six months. Ichthyosis has multiple modes of inheritance.
Materials and Methods
• Once the symptoms were assessed, possible genetic diseases were considered.
• A family history was determined through a genetic questionnaire and a pedigree was created.
• DNA samples were taken from the patient, her mother and father, the maternal grandparents
and the paternal grandparents.
• These DNA samples were run through agarose gel electrophoresis.
The agarose gel, containing 5mLof EtBr, was poured and set into the gel mold. Once it was
set, a buffer solution was added.
The appropriate wells of the set gel were loaded with 5mL of the dyed DNA samples from
the family and gel was run.
The gel was removed from the buffer solution and viewed under UV light.
•The gel was analyzed and the carriers of the allele for the disease were determined.
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 patient
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III-4
II-3
II-4
I-1
Figure 1. Pedigree of patient’s family which revealed the genetic disease as an xlinked recessive trait. Family member I-3 and I-4 were identified to be XaY and
XAXa respectively. Family member II-3 and II-4 were identified to be XAY and XaXa
respectively. Family members III-1, III-2, and III-3 were identified to be XAXa, XaY,
and XaY. The patient, III-4, was determined to be XAXa and thus carries the allele.
1-4
None of the patient’s family members died from their symptoms, so it was assumed that the
genetic disease is not life-threatening. The symptoms were clinically examined and characterized to
be thick, dark scales with an irregular to rhombic shape. When the scales were removed, a bright
red base with pinpoint bleeding was revealed. The family members described the affected skin
areas as very dry with mostly mild itching and only the paternal grandfather reported basal cell
carcinomas. The first sign of symptoms in each case was approximated to be between birth and the
first four months of life.
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III
Marker
A 16-year-old woman from Syracuse, New York came to a genetic counselor with a history of
family members having scaly skin on the scalp, ears, neck, abdomen, legs and feet. She was
concerned with her likelihood of acquiring these symptoms and then someday passing them on to
her children. In order to address the patient’s concerns, the symptoms of the family members were
examined through a family history and several possible genetic diseases were considered and
compared.
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II
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Introduction
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I-2
Genetic testing is very important when determining the inheritance of a genetic disease. In
this case, a patient came to a genetic counselor explaining a possible disease appearing to run
through parts of her family. The symptoms were assessed, a family history was taken, a pedigree
was made from the family history, and a gel electrophoresis was run containing the DNA of several
family members to determine the alleles of those in the pedigree. Through analysis of the gel and
pedigree, the genetic disease was determined to be X-linked ichthyosis. Because of the
transmittance of this genetic disease, the patient was determined that she will never show signs of
the disease because she is only a carrier of the recessive allele, and she has no chance of having
an affected daughter, but a 50% chance of having a daughter carrying the gene. The patient also
would have a 50% chance of having a son with the disease and a 50% chance of having a son
without the gene.
Discussion & Conclusions
Results
I-3
Abstract
Figure 2. Agarose gel containing DNA of family members I-4, I-3, I-2, I-1, II-4, II-3,
and III-4. With the help of the pedigree, it was possible to identify the alleles of
those family members along with other family members who’s DNA were not run
through the gel. Family member 1-4 and III-4 both have two bands visible in the
gel, but do not express the trait in the pedigree, so are both heterozygous for Xlinked Recessive Ichthyosis. Family members I-3 and II-4 each only has one band
with the smaller allele visible on the gel and express the trait in the pedigree, so
both only have the recessive allele. Family members I-2, I-1, and II-3 all have only
one band on the gel with the larger allele and do not express the trait in the
pedigree, so all only have the dominant allele.
•The pedigree (Figure 1) showed an X-linked inheritance pattern for the disease with the
maternal grandfather, mother, and two sons showing symptoms of the disease, but the two
daughters of the affected mother showed no symptoms
•The gel (Figure 2) made it evident that the disease was recessive because family members that
showed symptoms of the disease only showed the recessive allele and carriers of the disease
had both alleles present
•The disease Ichthyosis was determined to be the correct disease based on the symptoms and
pattern of inheritance (X-linked recessive) because Psoriasis had no apparent form of inheritance
and Hyperkeratosis lenticularis perstans was an autosomal dominant inheritance
X-linked ichthyosis is a relatively common genetic genodermatosis with a recessive X-linked
mode of inheritance, affecting 1:6000 males. (Hernandez-Martin, 2005)
Most cases of X-linked ichthyosis are caused by deletions of the steroid sulfatase gene (STS).
(Hazan, 2005)
•Symptoms of X-linked ichthyosis include onset at birth, and scaling on the scalp, ears, neck,
abdomen, front of legs, and dorsum of feet (OMIM)
•Joanna is a carrier of the disease because her mother is homozygous recessive for the disease
(XaXa) and her father is unaffected, which means Joanna received a dominant allele from her
father and the recessive allele, which carries the disease, from her mother
•Joanna will never show symptoms of the disease, but it is a possibility that the recessive allele
will be passed onto her children
•Joanna has a 50% chance of having a daughter that is a carrier of the disease, but a daughter
would not be affected (Figure 3)
A son of Joanna has a 50% chance of being affected by the disease
•No known cure (Rubeiz & Kibbi, 2003)
•Social discrimination and psychological affects are common to those who suffer from the
disease (Rubeiz & Kibbi, 2003)
•Possible therapies/ treatments: (Traup & Burgdorf, 2007)
•Newborns in intensive care
watch skin for infection
monitor temperature and fluids (should be in lower temperatures)
apply non-medicated cream to body
check vision and hearing
•Infants
bathe in sodium bicarbonate
rub affected areas with a cloth or towel
apply non-medicated cream to rash area
keep external area of ear clean
physical therapy
•Children/Adults
same treatments as newborns and infants but a urea cream should be applied to the
affected area (stronger concentration on scalp)
on warm or hot days exposure to sun should be kept at a minimal, and avoid warm
climates
References
Beveridge, G.W. “Familial Hyperkeratosis Lenticularis Perstans Associated with Tumors of the Skin.” British Journal of
Dermatology, 88: Page 453-457. Department of Dermatology, The Royal Infirmary, Edinburgh. Nov. 1972
Hernandez-Martin, A. “X-linked Ichthyosis in a Girl: Strategy for Identifying the Casual Mechanism.” British Journal of
Dermatology, vol: 152, iss:1, page 191. 2005
XA
XA
Y
XAXA
XAY
Xa
XAXa
XaY
Figure 3. Punnet square revealing the probability of the patient passing the trait
on to her children. If she has a daughter, there is a 50% chance that she will carry
the gene and a 50% change she will not carry it at all. There is no chance of the
patient having a daughter expressing the disease. There is a 50% chance of the
patient having a son having the disease and a 50% chance that the son will only
have the dominant gene.
Hazan, C. “X-linked Recessive Ichthyosis.” Dermatology Online Journal, 11(4), page 12. Department of Dermatology, New York
University School of Medicine. Dec. 2005.
Matthews, D. “Evidence that a Locus for Familial Psoriasis Maps to Chromosome 4q.” Natural Genetics, 14(2): pages 231-233.
Department of Biochemistry and Molecular Genetics, Imperial College School of Medicine at St Mary’s, Paddington, London,
UK. Oct. 1996.
<http.//www.ncbi.nlm.nih.gov/
Online Mendelian Inheritance in Man. (2007). Ichthyosis, X-linked. National Center for Biotechnology Information. Retrieved
September 27, 2007, from http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=308100
Rubeiz, N. & Kibbi, A-G. (2003). Management of Ichthyosis in Infants and Children. Clinics in Dermatology, 21, 325-328.
Traup, H. & Burgdorf, W.H.C. (2007). Treatment of ichthyosis- There is always something you can do! In Memoriam: Wolfgang
Küster. Journal of American Academy of Dermatology, 57, 542-547.