These results clearly show that array comparative genomic hybridisation should be considered to be an essential aspect of the genetic analysis of patients with syndromic ASD. Moreover, besides their importance for diagnosis and genetic counselling, they may allow the delineation of new contiguous gene syndromes associated with ASD. Finally, the detailed molecular analysis of the rearranged regions may pave the way for the identification of new ASD genes.

A lzheimer's disease, the most common cause of dementia in later life, is genetically heterogeneous. Mutations in three genes encoding the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are responsible for autosomal dominant early onset cases. A few families have been described in which PSEN1 mutations, usually exon 9 deletions, cause progressive dementia associated with spastic paraparesis. [1][2][3][4][5] We present a family in which another PSEN1 mutation causes disease that begins with spastic paraparesis and is associated with dementia that is not of the Alzheimer type.The index case first presented at the age of 54 with lower back pain and gait difficulties; he was unable to squat unaided and walked with caution. He complained of a memory deficit that he attributed to the Algerian war, 34 years ago. On examination, he had brisk reflexes in all four limbs and normal muscle tone. Blood cell counts, CSF glucose and protein levels, electromyography, and nerve conduction velocity were unremarkable. A lumbar CT scan and cervicothoracic MRI showed no signs of spinal compression. Brain MRI showed mild cortical atrophy.One year later, the patient had a bilateral extensor plantar reflex, with clonus of the patella and proximal muscle weakness in the lower limbs. There was no sign of cerebellar ataxia, and sensory modalities of the trunk and limbs were not affected. A second brain MRI showed mild cortico-subcortical atrophy. He was referred to our clinic at the age of 55 with the diagnosis of spastic paraparesis. He could not walk for more than one mile and complained of frequent falls. Gait was markedly spastic, but muscle tone at rest was normal. In addition to the pyramidal syndrome, there was gaze evoked nystagmus, saccadic ocular pursuit, and marked orthostatic hypotension. Dementia was evident, with a Mini Mental Status Examination (MMSE) score of 18/30 with deficits in visuospatial organisation and memory but no signs specific for Alzheimer's disease. Somatosensory evoked potentials and VLCFA (very long chain fatty acids) dosage were normal.At the age of 57, the neurological examination was stable. The patient had a single generalised tonic-clonic seizure when he was 58, a brain CT scan showed global atrophy, and EEG was normal. Examination at the age of 60 showed additional signs: fasciculations of the tongue, facial hypomimia, and cramps during the night. There was gestural apraxia without dressing apraxia and a sustained nasopalpebral reflex. A detailed neuropsychological examination was performed, showing decreased global efficiency, with an MMSE score of 14/30 (temporospatial subscore 2/10).There was a deficit in long term memory, without impairment of recognition capacity, but no short term anterograde memory with no alteration of retrograde memory. There was no aphasia, ideomotor apraxia, or agnosia. Only visuospatial abilities were affected. Finally, neither anosognosia nor frontal behaviour was evident.At the age of 61, he was able to walk with a walker and was able to...