Hasham Muhammad Jamil Trust (‘HMJ’ trust)
Registered Charity no: 1041708
LOC Syndrome
Laryngo-onycho-cutaneous (LOC) syndrome is a disorder that leads to abnormalities of the voicebox (laryngo), finger- and toenails (onycho), and skin (cutaneous).
Other names:
SHABBIR Syndrome (named after Professor Shabbir of King Edward VII hospital in Lahore Pakistan) who first observed the disease pattern.
LOGIC syndrome
JEB-LOC – this has been the most recent version of LOC – giving a nod to its link with Junctional Epidermolysis Bullosa – see below.
Occurrence:
Prevalence is unknown.
Fewer than 100 cases mostly in consanguineous families from the Punjabi region of Pakistan and India.
Clinical Features:
Many of the signs and symptoms of LOC are related to the abnormal growth of granulation tissue.
This red, angry, bumpy tissue is normally produced during wound healing and is eventually replaced by skin cells.
In LOC syndrome, this tissue grows even when there is no major injury and fails to completely heal
Signs often develop a few days after birth including:
Blisters and marks on the skin that are slow to heal or do not heal
Fragile skin that is easily bruised or peeled away causing blisters
Hoarse cry indicating involvement of the larynx which can lead to a blocked airway. This can sometimes lead to life-threatening breathing problems.
Chronic eye lesions causing gradual closure of the eyelids and adhesions to the eyeball. These can cause problems with vision and blindness if not treated surgically
Nails may fall off after being pushed up from the nail bed with abnormal healing (granulation) tissue leaving raw areas over the tips of the fingers.
Small abnormal teeth – the hard outer layer of each tooth (enamel) is thin and can cause cavities.
Problems with passing water – the urethra is often affected and can partially close. Children may need a catheter to be able to pass water comfortably.
Cause:
LOC syndrome is caused by mutations in the LAMA3 gene, which provides instructions for making one part (subunit) of a protein called laminin 332. This protein is made up of three subunits, called alpha, beta, and gamma. The LAMA3 gene carries instructions for the alpha subunit; the beta and gamma subunits are produced from other genes.
The Location of the gene is on the long arm (q) of chromosome 18 at position 11.2 (Specialists refer to this as 18q11.2)
The laminin 332 protein plays an important role in strengthening and stabilizing the skin by helping to attach the top layer of skin – the epidermis – to underlying layers. Studies suggest that laminin 332 is also involved in wound healing. Additionally, researchers have proposed roles for laminin 332 in the clear outer covering of the eye (the cornea) and in the development of tooth enamel.
The mutations involved in LOC syndrome alter the structure of one version of the alpha subunit of laminin 332 (called alpha-3a). Laminins made with the altered subunit cannot effectively attach the epidermis to underlying layers of skin or regulate wound healing. These abnormalities of laminin 332 cause the cutaneous erosions and overgrowth of granulation tissue that are characteristic of LOC syndrome. The inability of laminin 332 to perform its other functions leads to the nail and tooth abnormalities that occur in this condition.
Genetics:
LOC syndrome follows an autosomal recessive pattern of inheritance.
This means that if both parents carry the gene but are unaffected then there is a 1:4 chance of a child being born with the illness and 2:4 chance of a child being a carrier of the disease.
Most but not all of the effected children are from consanguineous marriages ie the parents are related eg cousins.
Long term prognosis
Prognosis is poor and many children die before the age of five.
However the severity of LOC tends to vary and some children do survive into adult hood and the disease seems to ‘burnout’.
Related Diseases
LOC is a subtype of Junctional Epidermolysis Bullosa (JEB). In this disorder individuals have very fragile skin that blisters easily. However unlike LOC syndrome they do not have overgrowth of granulation tissue in the eyes.
‘Debra’ is an international medical research charity dedicated to the curing of Epidermolysis Bullosa
For more advice and information of EB: