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With a prevalence of approximately 1:4000 interstitial chromosome 22q11 deletion within the DiGeorge syndrome critical region is the commonest chromosome microdeletion syndrome. The better known clinical features of this disorder are cardiac abnormalities, short stature, palatal abnormalities or velopharangeal insufficiency, renal abnormality, hypocalcaemia, psychotic symptoms, learning difficulties, and developmental delay.1
There is wide variability in this clinical spectrum and many case reports drawing attention to new clinical features have been published. Alongside the larger studies of 22q11 cohorts these have proved useful in delineating this particular syndrome.
We present a family where the proband at 3 years of age exhibited the typical facial features of deletion of chromosome 22q11 (fig 1a) of low set posteriorly rotated ears, small mouth and mandible, short philtrum, and short palpebral fissures, as well as developmental delay. His height was on the fourth centile and he also had pectus carinatum. His mother (fig 1b) also had learning difficulties and delayed motor milestones as a child and subsequently developed an unusual movement disorder, which was first noted as a tremor at age 5 and was brought to medical attention in her teens. The movement disorder consisted of longstanding pronounced myoclonus of the head, trunk, and limbs, which is worsened by intention and exacerbated by startle. She had slow tongue movements. Eye movements were normal. Extensive neurological investigations were normal: caeruloplasmin, molecular testing for Huntington’s disease, myotonic dystrophy, mitochondrial mutations, muscle biopsy, electroencephalography, and magnetic resonance imaging of the brain. Echocardiography and renal ultrasound in both mother and son were also normal. Although standard cytogenetic testing showed a normal karyotype, fluorescence in situ hybridisation analysis with the probe for the DiGeorge syndrome critical region showed that both mother and son had a deletion in this region.
In the European collaborative study presenting data on 558 patients with deletions within the DiGeorge syndrome critical region of chromosome 22q111 neurological details were available for 548 patients and 8% had neurological abnormalities. Three per cent had structural brain abnormalities such as cerebral atrophy, cerebellar hypoplasia, cerebral vascular abnormality, septum pellucidum cyst, hydrocephalus, hypoplasia of the corpus callosum, and enlarged ventricles. Eleven patients had asymmetrical crying facies, three had seventh cranial nerve palsies, and two had facial asymmetry. Seizure information was available for 290 patients of whom 21% had seizures, and in 42 these were hypocalcaemic in origin. Nine per cent of children were reported to have either behavioural or psychiatric problems and 18% of adults had a psychiatric disorder.
There has been no previous association with a similar neurological disorder and microdeletion 22q11, although a parkinsonian-like movement disorder has been reported.2 In that case extrapyramidal symptoms (muscle rigidity, oral-buccal movements, and tremors of his tongue and upper extremities) predated the onset of psychotic symptoms at 15 years of age.
As the mother of our proband first exhibited signs of a movement disorder at age 5 it will be interesting to see how he develops. Despite extensive neurological testing for the cause of the myoclonus in the mother, no cause was found. Three mutated genes for myoclonus-dystonia have been described in the literature, the most recent in 2001,3 and are not available as a diagnostic service. However, the phenotype we describe is different from that described in these cases: alcohol sensitive jerks, dystonia, usually torticollis or writer’s cramp, and often showing prominent psychiatric abnormalities. 22q11 microdeletion syndrome is a variable disorder and even within families signs can be very different. It is possible that many patients with physical and psychiatric abnormalities have an unrecognised genetic disorder. Increased awareness and access to testing may show a widening of the phenotypic spectrum of these disorders. We believe myoclonic movement disorder may be a previously unreported clinical feature of the chromosome 22q11 deletion.
Competing interests: none declared
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