Medical &
X-Linked Ichthyosis


Ichthyosis is a symptomatic description of a scaly skin appearance in humans which may vary in severity and extent.  The term "ichthyosis" means "fish like," referring to the scale-like appearance on the skin, similar to the scales on a fish.  There are many types of ichthyosis, with different causes, and ranging in severity from barely noticeable to very extensive and severe. 

Medical description tend to call Ichthyosis a genetic disease because it seems to run in families in a predictable pattern.  Some types of ichthyosis are debilitating and in some cases life threatening.  The root cause of ichthyosis appears to be a defect or mutation in the coding sequence of our DNA.  Mutations are occasionally helpful, though most are harmful.  I have yet to discover a helpful aspect to ichthyosis.


Humans have 46 chromosomes arranged in 23 cross-linked pairs. Each chromosome pair is a different type, and all 23 types are necessary to create a new human.  Each type of chromosomal pair looks the same in male and females, EXCEPT the 23rd Chromosomal pair.  The 23rd chromosomal pair (the gender-determinant chromosome pair) is different in males and females.  A female will have an X-X chromosome pair.  And a male will have an X-Y chromosome pair. 

Each chromosome pair is composed of a leg (segment) from the mother and a leg (segment) from the father.  Every cell in a person's body contains a complete copy of all 23 pairs of chromosomes, EXCEPT the ova (eggs) of a female, and the sperm cells of a male.  In the formation of ova and sperm cells, all 23 chromosome pair have split into two separate pieces in a "soup" from which the body selects a random leg of each type to form an ova (egg cell) in a female, or a sperm cell in a male.  This random selection process mixes the genetic contributions of preceding generations.

Each ova and each sperm cell so created has only one leg of each chromosome type.  In a female, the 23rd chromosome pair (X-X) splits into two separate X-legs, forming two eggs, each with only one X-chromosome.  In the male however, the 23rd chromosome pair splits into an X-leg sperm (gynosperm) and and a Y-leg sperm (androsperm.) 

On mating of a male and female, the union of a sperm and ova cell results in the individual leg-types from the father, and those from the mother, to connect into a new chromosome-type pair, each new pair containing half the DNA of each parent (and portions of preceding generations).  The new set of 23 chromosome pair set contains all the genetic coding that directs the formation, organization, growth, and appearance of a new human being.   

While an X-chromosome appears in both males and females, the Y-chromosome only exists  in males.  In fact, the Y-chromosome can only be passed from father to son, and does not pass through mothers or daughters.  In that sense, it is the "paternal-line" chromosome.

However our concern with X-linked ichthyosis is with a defective X-chromosome, which may be passed by either mother or father.


X-linked recessive ichthyosis is caused by a deficiency in the enzyme that produces steroid sulfatase, which is necessary for skin cells to be able to separate and shed normally.  The deficiency exists because of a mutation or defect on the STS gene located on the X-chromosome.  The defect is expressed as ichthyosis primarily in males with the defective gene on the X-chromosome.  However females with both X-chromosomes affected will also express ichthyosis. 

The visual expression of ichthyosis is a thickening of the skin (because the individual outer skin cells aren't separating and shedding as they should).  The thickening skin leads to a hardening and eventual cracking of the thickened skin, forming the characteristic pattern of scales. 

In the discussion that follows, we will designate the defective X-chromosome as a green X.  A normal X-chromosome will be designated as a white X, or another light color.  The X-chromosome, along with the Y-chromosome, are sex determinant chromosomes.   Normal females have an X-X set, and normal males have an X-Y set.   

A normal male will have an X-Y chromosome set.  An affected male will have an X-Y chromosome set.  Because the affected male does not have a normal X-chromosome, steroid sulfatase cannot be produced, and ichthyosis is expressed. 

A normal female will have an X-X chromosome set.  A carrier female has an X-X chromosome set.  An affected female has an X-X chromosome set.  The presence of a normal X-chromosome in the carrier female allows the production of steroid sulfate, so the carrier female does not express the thickening skin condition.  An affected female has no normal X-chromosome and cannot produce steroid sulfatase, resulting in ichthyosis being expressed.

An affected father and a carrier mother is required to produce an X-X affected female child.  An affected father and an affected mother will produce only affected children, male and female.  Generally these cases occur primarily in unions of closely related family members, such as in incest and in cousin marriages.  But it can also occur in unions of unrelated affected families.  Such unions reinforce the defective vector, and for this reason should be avoided. 

Other than being expressed in males, and only rarely in females, there are no known external characteristics which identify a female carrier.  Only a genetic test, or the existence of an affected father, or the birth of an affected son, (and rarely a daughter) confirms the female as a carrier.  A complete family history can suggest the possibility of a female being a carrier. 


The basic possible inheritance patterns are Cases A, B, C, & D are discussed and depicted below. 

Case A, consisting of a normal mother and an affected father, is where most genealogical investigations into origins will likely start.  Because the further back in time we go, the less information we can mine -- and an afflicted male is the most obvious to be recorded or remembered. 

For example The furthest back I can reach is my maternal grandfather, W. G. K..  I know from personal observation, and my mother's comments, that her father was afflicted with ichthyosis.  I have little to no information on W.G.K.'s antecedents.

I also know that none of my mother's brothers were afflicted, and none of the descendents of her brothers were afflicted. 

That I have ichthyosis is proof that my mother was a carrier.  There are no known cases from my father's side.  My grandfather fits perfectly into Case A -- where a daughter carrier occurs, but no sons suffer or carry the disease.

Case B, consisting of carrier mother and a normal father, is the normal successor generation to Case A. 

My mother fits  into Case B. Each of her male offspring had a fifty percent chance of inhering the disease and manifesting it.  In fact both of her sons manifested it, and at least two of my mother's three daughters were carriers.

X-linked recessive ichthyosis normally follows a pattern of alternating generations between case A and Case B.  Case A offspring are the skip generation -- no overt signs of ichthyosis manifest in the offspring.  Case B offspring are the afflicted generation -- overt signs of ichthyosis are displayed in male offspring.


Case C, consisting of a carrier mother and an affected father, introduces the possibility of producing an affected daughter.  While this occurs rarely, it does occur, primarily in closely related individuals within an affected family, or in the union of unrelated individuals from different affected families.

Case C begins the concern that closely related individuals with a family history of ichthyosis should seek genetic testing prior to forming a union that could produce children.


Case D, consisting of an affected mother and an affected father, raises the odds to 100% that all the offspring will be affected.  When this occurs, the union of very closely related affected individuals should be investigated, although it can also occur from the union of unrelated affected individuals.

Cases C&D gives impetus to couples with incidents of ichthyosis present within the both familial lines to seek genetic counseling, and testing.  Case D cries out that no progeny from such a union issue, as it would reinforce the defect within descendants. 



Manifestations of ichthyosis disappear in hot humid climates, except if air conditioning is habitually used.  It is also reduced or eliminated with prolonged exposure to sun, ocean humidity and the regular occurrence of sweating through physical exertion.  It is generally mild in summer and humid weather, unless air conditioning is used.  In dry and cold weather, and in air conditioned interior climates, manifestations of ichthyosis appear and are sustained.  The longer it goes without topical treatment, the thicker the skin platelets grow, and the stiffer the skin becomes, eventually developing cracks and fissures to accommodate the movement of limbs and muscles.


There is no known cure for the condition.  In the future, the possibility of gene therapy may offer some hope.  In case A, if there are no daughters, and only sons, the defect is purged from succeeding gene pool.  However, in Case B, C, and D, the defect can propagate unnoticed through successive generations of daughters. 


The epidermal manifestation of X-linked ichthyosis is the failure of outer skin cells to separate from each other laterally and from the adjacent layers underneath.  This causes the outer skin layers to become thicker and harder, and it also becomes more difficult for the inner skin layers to distribute moisture to the outer layers.  The result is that the outer skin layer becomes ever thicker as the inner layer continues to produce new skin cells.  The skin's thickness continues to interfere with moisture distribution and the skin becomes hard and brittle.  Movement of limbs and muscle cause the hard, brittle skin to break in irregular shaped platelets, giving the appearance of fish scales.  The layers of dead skin cells are bonded very strongly to each other.  If you try to pull off the "scales," it will likely pull off the new underlying developing skin cells, causing them to  bleed.

Topical exfoliating moisturizing lotions are the treatment of choice.  Exfoliation agents are necessary to induce the built up skin platelets to de-bond and flake off.  Moisturizing agents are necessary to soften the skin platelets so the exfoliating agents can penetrate through the built-up layers.

The two best commercial, over-the-counter product I have found are:
1) AmLactin (from Upsher-Smith), which contains 12% Ammonium lactate - a strong (though harsh) exfoliate, best for sever encrustations of the skin. 

2) Jergens Skin Smoothing Lotion (Jergens), which may contain about 1% Lactamide MEA - a light (and gentle) exfoliate with other exfoliating ingredients., beat for mild encrustations of the skin.     

AmLactin is the stronger exfoliate.  It both moisturizes and exfoliates.  It tends to darken the dead skin and make it look worse.  It is sold in Walgreen, Randall, WalMart, CVS, and COSTCO.  COSTCO has the best price, around $13 to $15  for the large size -- 17 oz. (500 gram) bottle.  The others sell the same bottle for around $24, or nearly twice as much.

Jergens Skin Smoothing Lotion is a much milder exfoliate, and primarily a moisturizer.  It does not darken the dead skin.  It is sold everywhere for less than a third the price of AmLactin.   

Another product is Lac-Hydrin.  It is a compounded by a pharmacists, or the pharmacy may have a ready-to-dispense supply.  It is more expensive than AmLactin, requires a prescription from a medical doctor (adding to the expense), has some adverse side effects because it is not properly buffered, and, in my opinion, it is inferior to AmLactin.

If your "scales" are fairly thick, it might take a few weeks of daily AmLactin use before you get down to normal-appearing skin.  You might even want to apply AmLactin more than once a day for really thick build ups.  Resist the temptation to pull off the scales.  It is better to scratch around the loose edges.  If the scale doesn't lift off easy, then leave it for later.  The best time to "scratch" is just after you have slopped on the lotion.  But scratch easy, and don't try to remove the scale build up all at once.      

Once you have used AmLactin, or an equivalent, long enough for your skin to appear normal, you may be able to cut back on your use of AmLactin, or switch to the more economical (and gentler) Jergens Skin Smoothing Lotion.  You can also mix the two to get a hybtid lotion with intermediate exfoliating strength.

Whichever you choose, you will want to use it often enough so that build up of layers don't re-occur.  You'll just have to experiment to see how often that is -- likely being daily in the winter, but perhaps much less often in the summer (unless your lot is in an air-conditioned building.)

CAUTION:  AmLactin, and also Lac-Hydrin, do not precisely imitate the body's natural process of exfoliating dead skin.  The over use of these two lotions will burn fresh skin.  If you (or the patient) is complaining of burning from the lotion, it is a sign that it is being applied too often.  When you have removed most or all the crust of dead skin, the daily application of AmLactin or Lac-Hydrin should be discontinued, and Jergens Skin Smoothing used instead, which will not burn fresh skin.

If the use of Jergens Skin Smoothing lotion results in a re-thickening of the skin, try mixing it with AmLactin before resuming AmLactin full strength, especially on children.    You will have to experiment a  little to discover the best application interval and/or mixture for yourself. 

Of the two commercial products, I much prefer Jergens over Am Lactin, both for cost and appearance.   Others may find Jergens ineffective. 

2010 Simon Revere Mouer III, PhD, PE, all rights reserved