Nail-patella syndrome
chromosome 9
Nail-patella syndrome (NPS) is an autosomal dominant disorder characterized by variable nail, skeletal, renal, and ocular abnormalities. The causative gene has been identified to be LMX1B, but not all families have showed clinically significant variants within this gene. A previous paper has suggested that a conserved upstream binding site called Lmx1b-associated cis-regulatory module (LARM2-bidning domain) can manifest in a milder nail-patella syndrome phenotype when deleted. Francis et al. identify a second family of 4 affected individuals with a separate, but overlapping LARM2 deletion, that segregates with clinical features of nail-patella syndrome, which further highlights how LARM2 deletions are responsible for a subset of unsolved NPS families. Microarray analysis revealed a 4-kb heterozygous deletion at 9q33.3 that was 82 kb upstream of the LMX1B gene. The deletion is de novo in the mother of three affected children; the proband is the eldest child, a 6-year-old female. Her development was appropriate, apart for mild language delay. She presented with dysplastic nails, intoed gait, limited supination of the forearms bilaterally, alternating esotropia and hypermetropia, although it is not clear whether her eye abnormalities were related to NPS. She had no renal abnormalities upon workup. Her mother had dysplastic thumb nails since birth, a history of knee pain, small patellae, and increased carrying angle at the elbow bilaterally. Her renal ultrasound and ophthalmological examination were normal. The proband’s younger siblings are dizygotic twin boys who presented with bilateral nail dysplasia and had normal renal ultrasounds and ophthalmologic evaluation. The authors also highlight how the three children could have renal symptoms emerge in adulthood; however, as it stands, this family supports previous literature that deletions of LARM2 yield more mild forms of NPS, further elucidating its variable expressivity.
Francis et al. “De novo enhancer deletion of LMX1B produces a mild nail-patella clinical phenotype”. “Clinical Genetics” 2023, v. 105(2):214-219.
Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. For more information on any article please contact info@chromodisorder.org
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