These vary enormously. At the mildest end of the spectrum the testicles may be undescended. The penis may be small and the scrotum poorly developed. The foreskin may be poorly developed or in part missing. Sometimes "hypospadias" is present, when the exit for the urine is not at the end of the penis but along the shaft. In a few children, the appearance of the genitalia makes the child's gender unclear or else appears to be female. The children do not have wombs or ovaries but small poorly formed testes may be found during exploratory surgery.
The development of the genitalia depends on the presence of the male sex hormones which are principally made by the testes. The problems of genital development seen in ATR-X syndrome are probably due to inadequate amounts of male hormones and this may also be the reason for some of the children not passing through puberty normally. Paradoxically, in a few children, sparse public hair may be present in early childhood and the cause of this is unclear.
These are rather diverse and may become apparent as the children grow. Occasionally a child may be born with a club-foot deformity. Some joints especially the fingers may be in a fixed, flexed position. Curvature of the spine can occur with age and should be checked for.
A few children are born with abnormalities of the heart. These may involve holes between the chambers of the heart, or abnormalities in the heart valves. Some, but not all of these, require surgical correction.
These are uncommon and sometimes are found incidentally. One of the commonest problems is "reflux", when on emptying the bladder some of the urine shoots back up towards the kidney. This may predispose to urinary tract infections. In the first few years of life the growing kidneys are very susceptible to damage from infections and it may be necessary for children with this sort of plumbing, to have antibiotics to prevent such infections developing when they are very young.
Early feeding may be problematic due to poor sucking reflex and generalised floppiness. Feeding via a tube passed into the stomach may be required during the early months. Very occasionally, especially if feeding difficulties are prolonged in childhood, a feeding tube has been used which passes through the abdominal wall into the stomach (feeding gastrostomy).
Frequent regurgitation of food or vomiting are common though this often improves as the child gets older. In a recent study involving a pair of affected non-identical twins, a barium meal revealed that both children had episodic gastric pseudovolvulus. In this condition the stomach does not have the normal system of peritoneal ligaments and has a propensity to twist around itself. This obstructions the normal gastric emptying and the stomach contents are forced back up the oesophagus. A number of children have had surgery to prevent this reflux of food back up the gullet - an operation known as a Nissen's fundoplication. One family informed us that changing to a macrobiotic diet caused a stop to the regurgitation of food. We would be interested to know of other treatments that have been successful.
Swallowing may be rather uncoordinated in ATR-X syndrome - some of the children show an apparent reluctance to swallow the food in their mouths and not infrequently it "goes down the wrong way" causing episodes of choking. Many burp prodigiously and the copious dribbling that is so commonly seen in this condition may be related to incoordinated swallowing. In one or two cases ducts from the salivary glands have been repositioned to further back in the mouth in an attempt to reduce dribbling.
Drug treatments to reduce the production of saliva are sometimes used, but these can reduce the muscular contractions of the gut and the boys may be particularly sensitive to this effect. A few children have had episodes when the gut appears to have "gone on strike" and stopped the normal contractions that propel the contents along the length of the gut (an ileus in medical terminology). This may be due to abnormalities that have been observed in the nervous system in the gut that is meant to help with coordinating the contraction of the gut. This may also explain why many of the children suffer constipation.
Many of the children have short stature and their growth is consistently behind that of others of a similar age. In a few, growth is within the normal range in childhood but they fall behind during the growth spurt of the early teens.
The children are usually described by their parents as content, of a happy disposition and an affectionate nature. They exhibit a wide range of emotions- joy, enthusiasm, excitement, grumpiness, sadness - depending on their circumstances. There have been some reports of apparently unprovoked emotional outbursts with sustained laughing or crying. Sometimes there may be sudden changes of mood from "highs" to "lows". Like most children they love attention and play, especially noisy games, rough and tumble, water play and musical toys. Some children exhibit quite repetitive behaviour. They often put their hands into their mouths and may bite their hands. In a few cases the children may push, squeeze or hit their face or neck with a hand. The children usually settle down well at night and sleep. In two or three reports from parents their children have become very withdrawn and quiet for days on end and often not eating. They may become quite distressed if disturbed. The cause of these episodes, and particularly whether they are associated with illness has not been resolved and we would be grateful to know of any similar situations.
About a third of boys have epileptic seizures. In the main they can be well controlled with drug therapy. Some children who have fits in early childhood appear to grow out of them. A number of parents have reported jerking movements which are not associated with abnormal brain wave activity on EEG.