Photomyoclonus, diabetes mellitus, sensorineural deafness with nephropathy

Herrmann , Aguilar, and Sacks described the syndrome in three generations of a family, with 13 members having photomyoclonic seizures and progressive deafness, which appeared in the third decade of life. Soon thereafter, mild diabetes and progressive dementia appeared.

Clinical data . Nervous system. In the proband, photomyoclonic seizures began at the age of 20 years, as well as in the youth of her 2 sisters and cousins. Sometimes there were also large convulsive seizures (grand mal). In the fourth decade of life, a fairly rapid breakdown of the psyche began, characterized by increased excitability, memory loss and depression. Over the next 10 years, these changes led to deep dementia. Later, the course of the disease was characterized by increasing deceleration and slurred speech, the appearance of one-sided focal symptoms, including progressive hemiparesis, decreased sensitivity to the hemitype, hemianopsia, as well as mild ataxia of the extremities.

The kidneys . In 4 patients, kidney disease was detected. Of the three, it was only written that they had “kidney damage or Bright’s disease.” In proband, despite normal urinalysis, interstitial nephritis was detected during autopsy.

Endocrine system . All patients with this syndrome had diabetes mellitus. In proband, the fasting blood sugar reached 200 mg%. In three other cases, diabetes was indicated by a glucose tolerance curve.

Organ of hearing . In the fourth decade of life, progressive sensorineural deafness was first noted. It was found in 9 out of 13 sick family members. In one of the patients, deafness, progressing, reached a pronounced degree over a seven-year period. Data audiometric studies are not described.
Vestibular system . The results of functional vestibular tests are not shown.

Laboratory data . Pneumoencephalograms of the proband showed a slight expansion of the ventricles. On intravenous pyelograms of 2 patients, a moderately expressed blunting of the renal calyces was found. As shown above, there was an increase in blood sugar and a pathological glucose tolerance curve.

In 4 patients, a urinalysis did not detect cells or proteinuria. In proband, in the study of urine by chromatography on paper, an increased content of valine and leucine was found. In 3 other patients, however, the level of these amino acids in the urine was normal. The electroencephalogram of the proband showed a generalized sharp disorganization of the curve. In 2 patients, generalized island-wave activity was accompanied by myoclonic discharges and was unconsciously produced during light stimulation. In 2 other patients with light stimulation with a maximum speed of 15 flashes per second, pronounced myoclonic and convulsive reactions were noted.  

Pathology . The kidneys were somewhat small and granular. Some glomeruli were atrophic and capsular fibrosis was visible. In the epithelium of the distal and collecting tubules were grains of PAS-positive substance. In the gaps contained numerous casts. In the interstitium, small foci of lymphocytes and foaming macrophages were noted. These changes are similar to those observed with Alport syndrome.

Brain pathology was manifested by mild atrophy of the cortex. There was a loss of nerve cells in the brain, as well as, possibly, in the cerebellar cortex, in the dentate nucleus, and in the nucleus of the lower olives. 

Heredity . It seems that all patients in this family had the same disease. All young patients had mild diabetes mellitus and photomyoclonus. All senior patients had deafness and mental decay. However, in 2 sisters of 28 and 40 years of age, intelligence and hearing were normal. Among patients there was an equal number of men and women. Inheritance appears to be autosomal dominant with complete penetrance and varying expressivity.

The diagnosis . Progressive renal failure and sensorineural deafness occur in Alport syndrome. However, with this disease, mental disorders or epilepsy are never observed, except for terminal conditions when they accompany uremia. Myoclonic epilepsy is noted with (1) Lafora disease, which is characterized by rapidly increasing dementia and convulsive seizures, with (2) Unierricht myoclonic epilepsy, characterized by a very slow course, rigidity, cerebellar symptoms and dementia, with 3 sclerosing panencephalitis with a rapidly progressing course and with (4) accumulation diseases affecting the nervous system, including ugly diseases. Pi in one of these diseases deafness is not a leading symptom.

Myoclonic epilepsy with sensorineural deafness on the basis of its recessive inheritance and deep congenital deafness should be distinguished from the syndrome considered here . Myoclonic epilepsy with ataxia and sensorineural deafness is very similar to the real syndrome. However, the breakdown of the psyche is not a leading symptom of this disease.    

Treatment . Anticonvulsants should be used to treat myoclonus and grand mal epilepsy. Hearing aid can help with hearing impairment.
Forecast . Until the breakdown of the psyche sets in, foreshadowing death in a few years, the prognosis does not seem so poor.

Conclusions . This syndrome is characterized by:
1) autosomal dominant inheritance with varying expressivity;
2) photomyoclonic epilepsy, starting in youth;
3) mild diabetes mellitus starting in adulthood;
4) nephropathy with accumulation of PLCS-positive substance in the cells of the renal tubules and
5) progressive sensorineural deafness.