Development and behaviour
Evaluation of developmental skills from infancy ensures that the appropriate intervention services are introduced as early as possible. Infant stimulation, early intervention and special education are important to optimise abilities. Affected individuals may show improvement in socialisation with one-to-one therapy. Anti-psychotic medication such as prochlorperazine may be effective in treating severe behaviour problems.
Feeding and gastro-intestinal problems
Infantile hypotonia is very common and is associated with considerable difficulty with sucking. Gavage feeding may be required for a number of weeks to assure adequate nutrition.
Recurrent vomiting, regurgitation or gastro-oesophageal reflux, particularly in early childhood, is a common finding and may be secondary to gastric pseudovolvulus. Evaluation of recurrent vomiting should include assessment for gastro-oesophageal reflux and there is a strong case for 24 hr pH monitoring and barium study of the upper gastro-intestinal tract. Initial treatment for gastro-oesophageal reflux should be conservative and standard. Nutrition consultation for assurance of adequate caloric intake may be needed. In severe cases, surgical treatment by fundoplication may be indicated, as well as the introduction of a feeding gastrostomy. If gastric pseudovolvulus is demonstrated this requires surgical correction.
Prolonged periods of food and drink refusal associated with considerable distress are frequently reported by parents. The cause is rarely obvious, but peptic ulceration, oesophagitis or ileus should be considered, as these are well documented in this condition.
Constipation can be a significant management problem and fecal impaction may occur if preventative measures are not undertaken. Adequate hydration is important in preventing constipation, as is the use of bulking agents in the diet and the regular use of osmotic laxatives such as lactulose. If the problem is resistant to conservative management then rectal biopsy should be considered to exclude ultra-short segment Hirshsprung's disease and colonic hypoganglionosis.
Drooling is very common in ATR-X, particularly in young children. Many mothers will describe their sons soaking several bibs during the course of the day. The open mouth associated with facial hypotonia no doubt is an important factor, as is their reluctance to swallow even with a mouth full of saliva. Numerous methods have been tried to control drooling. Feeding by mouth may help encourage the swallowing reflex and this may be supplemented by specialist training by a speech therapist. In other conditions in which there is drooling, anticholinergic drugs are commonly used to reduce production of saliva. However, these drugs cause reduced gastrointestinal motility (which may already be abnormal in ATR-X males) and may exacerbate constipation or provoke ileus. Botulinum toxin type A (Botox) injection of the salivary glands might be tried, but reports are scant and the treatment needs repeating. The surgical options of redirecting the submandibular ducts or removing the glands themselves may be considered.
Spasticity may increase with age. Regular evaluations of the need for physical therapy are needed and ongoing therapy may ameliorate spasticity.
Seizures occur in approximately one third of cases and most frequently are clonic/tonic or myoclonic in nature. In the majority of cases, seizures respond well to standard therapy. Some affected individuals exhibit jerking movements which, though appearing to be seizures, are not associated with epileptiform activity on EEG. Electroencephalogram may need to be carried out with video recording to correlate seizure activity and abnormal movements. Approach to seizure control is standard.
In ATR-X syndrome about 90% of cases have alpha thalassaemia. The anaemia, however, is mild and does not require treatment. Iron is not indicated unless iron stores are shown to be low.
Genital abnormalities are seen in 80% children. The possibility of cryptorchidism should be assessed in all affected children. Orchidopexy should be carried out as required at the standard age. Intra-abdominal testes, which are usually dysgenetic, should be removed because of the long-term risk of malignancy.
Structural abnormalities of the kidneys and ureters are well described and may predispose individuals to urinary tract infections. Renal abnormalities (hydronephrosis, renal hypoplasia or agenesis, polycystic kidney, vesico-ureteric reflux) may present with recurrent urinary tract infections. The urinary system should be imaged with ultrasound at diagnosis. Urine should be cultured when there is symptomatology such as fever or pain on urination. Prophylactic antibiotics are indicated if urinary tract anomalies are present to prevent long-term damage to the kidneys.
A wide range of relatively mild skeletal abnormalities have been noted, some of which are probably secondary to hypotonia and immobility [14
]. Foot deformities occur in 29% of cases and include pes planus, talipes equinovarus and talipes calcaneovalgus. Kyphosis and scoliosis are common and increase with age. A careful musculoskeletal exam should be done at diagnosis and throughout childhood. Treatment of musculoskeletal anomalies, when appropriate, is standard.
Hearing and vision
Sensorineural deafness may be present. Standard distraction tests and, if anomalies are suspected, evaluation of auditory evoked responses should be done. Hearing loss should be managed as for any infant.
Refractive abnormalities, in particular myopia, are common. Strabismus may be present. Rarely the children may be blind and this may be associated with optic atrophy. A formal ophthalmologic evaluation is appropriate at diagnosis and regularly thereafter. Ocular problems should be treated as in the general population.