OMIM ID:
Birk-Landau-Perez Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Patients have oculomotor apraxia, saccadic pursuits, lack of fixation, and ptosis. No pigmentary changes were seen in the fundi but the optic nerves have not been described.
Systemic Features
This is a progressive disorder in which psychomotor regression and loss of speech develop by 1 to 2 years of age, often appearing as the first sign of abnormalities. Cognitive impairment can progress to profound intellectual disability. Older patients have limb and truncal ataxia and experience frequent falls. Muscle tone in the limbs is increased and children often exhibit dyskinesia, dystonia, and axial hypotonia. General muscle weakness is often present. No abnormalities have been seen on brain imaging.
Some patients develop a nephropathy with renal insufficiency, hypertension, and hyperechogenic kidneys though deterioration of the renal disease is slow. Renal biopsy in one patient revealed tubulointerstitial nephritis but no individuals have reached end-stage renal failure.
Genetics
Inheritance
Homozygous mutations in the SLC30A9 gene (4p13) are responsible for this disorder. A single multigenerational consanguineous Bedouin family of 6 affected individuals has been reported with a transmission pattern consistent with autosomal recessive inheritance.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.