12q14 microdeletion syndrome

Last revised by Arlene Campos on 12 Jan 2024

12q14 microdeletion syndrome or osteopoikilosis-short stature-intellectual disability syndrome is caused by heterozygous deletion at the region of 12q14. The microdeletion affects the LEMD3 gene which has already been implicated in osteopoikilosis.


Prevalence is <1 in 1 million live births. Whilst usually a spontaneous/de novo mutation, in <1% of cases both parents may have normal chromosomes noted on blood tests but few of their sperm or eggs carry the microdeletion. This would result in germline mosaicism and their subsequent children may have the same microdeletion. If inherited, it is passed on in a dominant pattern and the possibility of having another child with the microdeletion is up to 50% with each pregnancy (regardless of gender).

Clinical presentation

  • pregnancy

  • neonatal

    • feeding difficulties/failure to thrive

    • hypotonia that may contribute to poor latching

  • development

    • small for dates likely due to poor feeding

    • gastro-esophageal reflux

    • fine motor skills development have been reported, longer to grasp items or dress/feed themselves

    • delay in language development, learning difficulties

Other features include

  • osteopoikilosis: can be absent at birth and only develop in teenage years

  • irregular marks or lesions: yellowish areas of skin, increased pigmentation

  • cardiac pathology: VSD, ASD, PDA, hypertension, pulmonary stenosis

  • extremities: clinodactyly, joint laxity, single palm crease, large thumbs, short broad fingers

  • dental: late eruption of teeth

  • ocular: some reports of strabismus. hypermetropia

  • other: middle ear effusion requiring grommets, ectopic kidneys. scoliosis

  • neurodevelopmental: attention deficit hyperactivity disorder, autism spectrum disorder

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