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Lower motor neurone involvement is the main feature of several neurological disorders, including the various forms of spinal muscular atrophy (SMA). A distinct form of SMA is characterised by predominantly distal weakness and atrophy of the limbs.1 Various combinations of SMA with neural and extraneural defects, mainly pontocerebellar hypoplasia, have also been reported.2
We report a combination of distal SMA with Dandy-Walker complex and anterior polar cataracts in two brothers.
The patients were aged 25 and 23 years. Their parents, who originated from the same area of Greece, were unrelated and asymptomatic. Since the age of 10 years, both brothers presented with progressively deteriorating symmetrical distal muscle weakness and atrophy of the lower limbs, which affected mainly the anterior tibialis and peroneal muscles and, to a lesser degree, the gastrocnemius, resulting in an almost “stoke-like” appearance of the legs. Bilateral anterior polar cataracts had been diagnosed in both patients at the age of 9–11 months. Additional findings of the neurological examination in both patients were slight muscle strength reduction in both hands and forearms and decreased tendon reflexes in the upper and lower limbs, while the Achilles’ tendon reflexes could not be elicited. The plantar responses were normal. No sensory, cerebellar, or cognitive impairment was found. Dysmorphic features were not observed. The general physical examination was normal in both patients.
Extensive haematological, biochemical, and immunological investigation of both patients, including levels of creatine kinase, prolactin, hexosaminidase A, anti-GM1 and antisulphatide antibodies, cortisol, thyroid hormones, vitamin B12 and folic acid, immunoglobulin and lipoprotein electrophoresis, and cerebrospinal fluid examination, was normal.
The electrophysiological examination revealed findings compatible with anterior horns involvement in both patients. Specifically, the electromyogram showed chronic active denervation of distal muscles, with large amplitude motor unit potentials and presence of polyphasic potentials and spontaneous activity (fibrillations and positive waves), more pronounced in the lower limbs. Nerve conduction studies showed normal motor and sensory conduction velocities, with normal amplitudes, latencies, and F waves. No conduction blocks were recorded. Electrophysiological investigation of both parents was normal. Both patients refused consent for muscle biopsy.
Magnetic resonance imaging revealed the presence of Dandy-Walker complex in both patients. There was enlargement of the cisterna magna, with slight hypoplasia of the vermis and slight elevation of the tentorium (fig 1). No supratentorial or brainstem abnormalities were observed. The magnetic resonance imaging of the spine was normal in both brothers, as were visual and brainstem evoked responses. Ophthalmological examination confirmed the presence of anterior polar cataracts in both patients.
The karyotype was normal in both patients. Molecular genetic analysis for mutations in the survival motor neurone (SMN; exon 7 and 8 deletions), neuronal apoptosis inhibitory protein (NAIP; exon 5 and 6 deletions), and androgen receptor genes was negative.
Our patients were two brothers with almost identical clinical and laboratory findings. One of the main features was the involvement of the anterior horn cells, which was compatible with distal SMA, according to published criteria.1 Additional features were Dandy-Walker complex and bilateral anterior polar cataracts.
There are several reports of SMA with additional features (SMA plus), among them pontocerebellar hypoplasia. These cases, however, are characterised by proximal muscles involvement, early presentation with profound floppiness at birth, mental retardation, and cerebellar signs.3 There are also rare reports of recessive distal SMA with additional features: diaphragmatic paralysis or pyramidal signs.4 None of these cases of proximal or distal SMA plus has been linked to chromosome 5q.
Familial cases of Dandy-Walker complex are not uncommon; however, the combination of the disorder with SMA seems to be quite unusual. The aforementioned severe cases of pontocerebellar hypoplasia in SMA plus clearly constitute a different nosological entity.
The coexistence of early onset cataracts with neuromuscular disorders is also unusual. Apart from the well known occurrence of cataracts in myotonic dystrophy, there are some reports of cataracts in combination with spastic paraparesis, spinocerebellar degeneration or neuropathy, and facial dysmorphism.5 There is also a report of familial congenital cataracts and Dandy-Walker anomaly with lissencephaly. We were not able to locate in the literature any reports of distal SMA in combination with any form of Dandy-Walker variant and/or congenital cataracts.
In summary, our cases represent an unusual combination in distal SMA. This combination does not seem to fit in any of the already described syndromes and could be the result of pleiotropy, contiguous gene syndrome, or chance. The fact that the patients were first degree relatives and presented with identical phenotypes is a strong indication that the disorder is genetically determined. With the available information on the genetics of the main features of our patients, contiguous gene syndrome appears unlikely. We were not able to locate a genetic defect, a not altogether unexpected result, as most recessive distal SMA families remain to be genetically determined.2 Future investigation of similar cases should include genetic studies relevant to all three main features of the disorder.
Competing interests: none declared
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