1. Mid-face Toddler Excoriation Syndrome (MiTES) can be caused by autosomal recessive biallelic mutations in a gene for congenital insensitivity to pain, PRDM12
C Moss1,2, SM Srinivas3, N Sarveswaran4, M Nahorski4, VK Gowda5, FM Browne6, G Woods4,7.
Birmingham Women’s and Children’s Hospital, Birmingham, UK.
University of Birmingham, Birmingham, UK.
Department of Pediatric Dermatology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India.
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India.
Department of Dermatology, Our Lady's Children's Hospital, Crumlin, Dublin, UK.
Department of Medical Genetics, University of Cambridge, Cambridge, UK.
British Journal of Dermatology. DOI: /bjd.16893

2. Celia Moss, Birmingham UK Sahana Srinivas, Bangalore India Fiona Browne, Dublin Ireland Geoff Woods, Cambridge UK

3. Introduction What’s already known?
MiTES is a newly recognised condition, described in 3 children, characterised by severe, chronic, scarring, self-inflicted, midface excoriations, commencing in infancy.
MiTES resembles fabricated and induced illness.
The gene PRDM12 is responsible for an autosomal recessive disorder, hereditary sensory and autonomic neuropathy type VIII (HSAN8), characterised by congenital insensitivity to pain with ulceration to extremities
A family with mild manifestations of HSAN8 and MiTES lesions had homozygous mutations in PRDM12.

4. Objective We previously coined the term MiTES in 3 children1
We aimed to delineate the condition more clearly and find the cause.
In particular we wanted to explore the possibility of mutations in the pain insensitivity gene, PRDM12, since it had been implicated in 5 siblings with “perinasal picking”2.
Srinivas SM, Vykuntaraju KG, Owen CM, Moss C, Hiremagalore R. .Mid-face Toddler Excoriation Syndrome (MiTES): a new paediatric diagnosis. Clin Exp Dermatol Jan;42(1):68-71
Chen Y-C, Auer-Grumbach M, Matsukawa S et al. Transcriptional regulator PRDM12 is essential for human pain perception. Nature Genetics 2015;47(7):

5. Methods
Five children with MiTES were diagnosed on the basis of their facial lesions
Family history and clinical features were documented
Genomic DNA was isolated from the children and their parents
Targeted Sanger sequencing was carried out of all 5 exons of PRDM12

6. Results: facial appearance

7. Results: clinical features and genetic results
Sex
Country of origin
Parental consanguinity
Age at presentation
Age of onset
Duration of follow up
Generalised pain insensitivity
Neurological features
Thrombocytosis
Iron deficiency anemia and
mutation
Male
India
yes
4yr 9m
1yr no
Nil 
Homozygous or hemizygous PRDM12 18x Ala expansion
Female
Homozygous or hemizygous PRDM12 18x Ala expansion
2yr 8m
Homozygous PRDM12 18x Ala expansion
3.6yr 1y
Developmental delay
None found
Ireland
No 
18m 
 2yr
 Delayed speech
Compound heterozygous PRDM12 18/17x Ala expansion

8. Discussion (1)
Transcriptional regulator PRDM12 is essential for pain perception.
The polyalanine tract in the final exon of PRDM12 is polymorphic.
In healthy individuals the tract does not exceed 14 alanine residues.
Homozygous expansion up to 18 or 19 alanine residues causes Hereditary and Sensory Neuropathy type 8, HASN8
Facial scratching has been reported in HSAN8, along with damage to extremities.

9. Discussion (2)
In MiTES the polyalanine tract is increased to 18 residues.
This can be due to duplication (see diagram).
Mites can be considered a localised variant of HSAN8.
From: Chen et al Nature Genetics 2015;47(7):

10. Discussion (3) One child with MiTES had no mutation in PRDM12.
This indicates that MiTES is probably genetically heterogeneous.
This child also had significant global delay.
Children with Mites presumably suffer from
Dysaesthesia resulting in an irresistible urge to scratch
Reduced pain sensitivity so that the scratching is not moderated by pain

11. Conclusions What does this study add?
A further 5 children with MiTES, in 4 families, are reported.
Mutation analysis revealed biallelic mutations in PRDM12 in 4 children in 3 families. No mutations were found in the fifth child.
This confirms MiTES as a recessive disorder of pain sensation which is probably genetically heterogeneous.
This new finding will improve our understanding of children presenting with this condition.  

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