SSBP Information Sheet
LOWE SYNDROME

Alternative names: Oculocerebrorenal Syndrome of Lowe, Oculo-cerebro-renal Syndrome.

First Description: In 1952, Lowe et al described three patients with abnormal renal function, bone disease, mental retardation and congenital glaucoma. They suggested that these patients may have been suffering from a previously unreported syndrome which arose from an inborn error in metabolism. Later studies confirmed the existence of an X linked disorder (Lowe Syndrome) which caused major abnormalities in the eyes, nervous system and kidneys.

Incidence / Prevalence: Prevalence is estimated at only a few cases per 100,000 males.

Genetic Aspects: Lowe Syndrome is caused by a mutation in the OCRL gene known as OCRL1 and located at Xq25-26. This gene encodes a protein localised to the Golgi complex and a deficiency of this protein leads to a defect in phosphatidylinositol metabolism (Nussbaum and Suchy, 2001). This defect is thought to be the origin of the various developmental abnormalities associated with Lowe Syndrome and it’s discovery means that a biochemical diagnosis of the syndrome is now possible.

Physical phenotype: The three main systems affected by this syndrome are the eye, central nervous system and kidney. Congenital cataracts are always present before birth and glaucoma occurs frequently. Visual acuity is almost always impaired and additional ocular abnormalities include corneal scarring and keloids. Both the central and peripheral nervous systems are affected with neonatal hypotonia and areflexia present in all cases. A delay in motor milestones is also seen and seizures occur in many cases. Abnormal kidney function is one of the criteria for diagnosis and usually manifests as postnatal proximal tubular acidosis, aminoaciduria, phosphaturia and proteinuria. Progressive renal failure also occurs during the second and third decades of life. Muscoloskeletal complications are also common and may be the result of hypotonia, renal failure or the underlying disorder itself.

Cognitive aspects: A diagnosis of Lowe Syndrome is compatible with normal intelligence and approximately 10% of patients have intelligence within the normal range (Nussbaum and Suchy, 2001). However intellectual impairment is a common feature with median IQ in the moderately impaired range. Estimates of intelligence may be depressed due to the employment of tests which are not suited to individuals with visual impairment.

Behavioural aspects: Behaviour disturbances can be the most problematic aspect of Lowe Syndrome for parents and carers. Maladaptive behaviours are seen in over 80% of cases and include self injurious behaviour, aggression and episodic outbursts (also called Lowe tantrum) (Kenworthy et al., 1993) . These outbursts along with negativism, stubbornness and stereotypies were found to be characteristic of Lowe Syndrome when age, gender, visual impairment and cognitive functioning were controlled for (Kenworthy and Charnas, 1995).

Life expectancy: With appropriate treatment patients may live to be 30-40 years old with death usually occurring as a result of renal failure, respiratory distress, status eplilpticus or infection.

Key References

Lowe, C. U., Terrey, M. and MacLachlan, E. A. (1952) Organic-Aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation – A clinical entity. American Journal of Diseases of Children, 83, 164-184

Nussbaum, R. L. and Suchy, S. F. The oculocerebrorenal Syndrome of Lowe (Lowe Syndrome) In The Metabolic and Molecular Basis of Inherited Disease, 8th edition, Volume 4 (eds. C. R. Scriver, W. S. Sly, B. Childs, A. L. Beaudet, D. Valle, K. W. Kinzler and B. Vogelstein), 2001, New York; London: McGraw-Hill.

Kenworthy, L., Park, T and Charnas, L. R. (1993) Cognitive and behavioral Profile of the Oculocerebrorenal Syndrome of Lowe. American Journal of Medical Genetics, 46, 297-303.

Kenworthy, L and Charnas, L. (1995) Cognitive Evidence for a Discrete Behavioral Phenotype in the Oculocerebrorenal Syndrome of Lowe. American Journal of Medical Genetics, 59, 283-290.

K Berg & C Oliver, 2004