Corpus callosum agenesis
mental Retardation
Adducted thumbs
Spastic Paraplegia
Hydrocephalus
(i.e. missing connection between the brain (cerebral) hemispheres, delays in mental development, thumbs bent inwards into the palm of the hands, uncoordinated voluntary movements, enlarged ventricles (cavities) of the brain i.e. too much water (cerebrospinal fluid) in them)

The symptoms of the MASA syndrome were first reported in 1974, but it took some time until the disease received its name.

As time went by researchers found out that the MASA syndrome, X-related hydrocephalus and X-related spastic paraplegia were related disorders, all of which were located on the same gene (L1CAM, location: Xq28).

More and more researchers nowadays tend to unite these diseases in the CRASH syndrome.

The MASA (CRASH) syndrome is a very rare disease. Its symptoms vary a lot and can be mild to severe. It mainly affects males and is passed on from mothers to 50% of their children, but as the gene for the disease is located on the X chromosome and females have two X chromosomes to determine their gender, the "healthy X" is normally dominating and the femails remain unafflicted in the vast majority of the cases. As males have only one X chromosome (and one Y chromosome) to determine their gender they automatically develop the disease when they inherit the MASA gene. So a male with this gene passes it on to every of his daughters but to none of his sons (because the male's Y chromosome and one of the two X chromosomes of the female dictate the - male - sex).

Sometimes, however, it seems that the number of afflicted persons in a family (kindred) lies clearly under the statistic level. For example we have seven children (five boys, two girls) with only one boy suffering from the MASA syndrome. (Three more boys were tested and do not have the disease gene!)

There have been many theories about the causes - even in medical opinion.

One of the hypotheses was a to be present mosaic form which means that the mutation appears during the mitosis during the embryonic development which means that the zygote is not yet afflicted. In Andy's case this would have happened then with me. Depending on the moment during maternal development in which this happened it could be theoretically possible that not every immature egg-cell was affected. In this case less than 50% contained the X-chromosome with the genetic trait.

Another hypothesis is a trigger function of my hypothyreosis details of which can be found here. There can not yet be said a lot about the probability for the accuracy of this hypothesis.

Which leaves the hypothesis that it was just a lot of luck!! In the end only one of the two X-chromosomes are affected which meant a 50% chance for each child to develop from the X that is not affected...)

I (personally) am wondering whether their is a correlation between my hypothyreosis as a predestinating factor and the development of the disease itself or of afflicted germ cells as my hypothyreosis was diagnosed only a short time after my pregnancy with my afflicted son. (Since then I receive a treatment.) In addition, I have been told by other mothers with children with very similar clinical findings (but not MASA) that they had been suffering from hypothyreosis as well.

One must note, however, that this possible correlation is not backed by most health professionals.

But as the MASA syndrome is such an extremely rare disorder the search for possible (co-)causes must be done in several directions...

It has been diagnosed in about 50 cases, according to NORD (National Organization for Rare Diseases Inc., USA, 1988).

MASA afflicts the coordination of the voluntary movements - especially those of the legs - as well as the development of intelligence.

The varriation of symptoms appearing is vast. Some children develop only mild symptoms while others show the full range of physical and mental findings.

The following symptoms may be diagnosed:

hydrocephalus
(=too much brain water in the caves of the brain (ventricles) - either as a result of a narrowing of the aquaeduct for drainage or due th an excessive production of brain water).; with or without an enlargened head; with or without the necessity of an operation; sometimes ventricles are only slightly enlarged (no operation needed).

drink / feeding problems in infants and children
(e.g. newborns micght be too week to be breastfed or even fed with a bottle (ask me for tips, if you like), small children might have eating difficulties due to a low muscle tone (hypotonus) in the tongue and in the mouth area.)

Adducted thumbs, i.e. thumbs that are bent inwards into the hand and neither th afflicted individual nor another person can move the thumb far enough out of the hand.

Thus the ability of grasping is usually diminished.

Generally both thumbs are adducted, but sometimes one thumb is more afflicted than the other one.

Physiotherapy and / or a splint (worn during the night in order not to disturb grasping practice during the day) may be helpful and able to improve the situation (when applied from an early stage).

Hypertonus, i.e. a rigidity in the muscels, is fond in certain regions of the body which can be the shoulder area in an infant or the legs in a child, for instance.

Agenesis of the corpus callosum, i.e. the lacking of the thick band of fibres connecting the two hemispheres of the brain which results in a lack of coordinated voluntary mobements, often in a diminished mental development etc.

Primitive tongue movements which, together with a hypotonus of the mouth area, can make drinking, eating and learning to speak more difficult. Physiotherapie (e.g. Castillo Morales) may be helpful.

Intelligence deficits with the result of diminished learning capabilities (early training is important).

Diminished speaking ability due to brain defects and a hypotone mouth region / tongue.

Prominent forhead

Flat feet

Diminished ability to learn holding the head, turning round, sitting up, standing up and walking.

Reduced length of the tendons, e.g. in the knees as a result of a retarded development of walking (a longer period of crawling -> longer period of bending of the knees).

Defects of the spine (abnormal bending in different directions)

Other skeletal defects

Diminished growth (normally slightly)

Slightly different facial expressions and excessive salivation as well as a normally slight hanging out of the tongue due to hypotone facial muscles.

Spacticity (e.g. of the legs) (Physiotherapy!)

Squinting and possible slightly diminished ability to see properly due to a weakness of the eye muscles. (Ask your physiotherapist and a specialized doctor for the best therapies.)

Shuffling gait due to weakness and / or increasing rigidity of the leg muscles. (Physiotherapy!)

Difficulties to understand (mainly) speech.

Problems with stomach and intestines (e.g. our son vomits very often and also needs more nappies than other children do).

Note:
The information on the question whether the MASA syndrome symptoms become worse and more prominent in the course of time is rather crucial. In our son's case they didn't, but Andy is obly two years of age...

Later statement, January 2005:
In Andy's case the symptoms regarding his legs have worsened (more spasticity) though, but meanwhile he only rarely vomits and in his mental development as well as his speech he has made more efforts than expected.

It is important to note that the symptoms vary a lot and that not every afflicted individual shows all of them. Moreover, some persons develop only mild symptoms while others are severly afflicted. Apart from that the vast majority of afflicted persons is male (due the-above-mentioned-way the disease is inherited).

For more information, e.g. on related syndromes part of which are located on the same gene, see Rare Disease Database of NORD.

Now I would like to introduce you to the course of our son's form of the MASA syndrome (as a kind of case study with additional information on e.g. treatment). Our son's nickname is Andy. -> Andy's Story