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SHORT COMMUNICATION
Keratitis-Ichthyosis-Deafness Syndrome: Early Death Caused by the GJB2 Mutation p.Gly12Arg
Clothilde GODILLOT 1 , Maella SEVERINO-FREIRE 1# , Vincent MICHAUD 2# , Franck BORALEVI 2 , Christine LABREZE 2 , Vincent
GUIGONIS 3 , Giuliana ONNIS 1 , Fanny MORICE-PICARD 2 and Juliette MAZEREEUW-HAUTIER 1
Dermatology Department, Reference Centre for Rare Skin Diseases, 1 CHU Larrey, Université Paul Sabatier, 24 chemin de Pouvourville, FR-
31059 Toulouse Cedex 09 and 2 Hôpital Pellegrin, Bordeaux, and 3 Paediatric Department, Hôpital de la Mère et de l’Enfant, Limoges, France.
E-mail: [email protected]. # These authors contributed equally to the work.
Accepted May 16, 2019; E-published May 17, 2019
Keratitis-ichthyosis-deafness (KID) syndrome is a rare
disorder caused by mutations in GJB2 encoding connexin
(Cx) 26. Cxs are membrane proteins that are primarily
involved in intercellular communication. Six Cx molecu-
les are oligomerized to form a connexon (hemichannel),
which docks at cell–cell contact points to form a gap
junction intercellular channel that allows exchanges be
tween neighbouring cells. The p.Asp50Asn mutation is a
recurrent mutation (80% of patients), but other mutations
have also been reported, namely p.Gly12Arg, p.Asp50Tyr,
p.Ser17Phe, p.Gly45Glu, p.Gly12Cys and p.Ala88Val (1).
KID syndrome is an autosomal dominant condition with
some familial cases, but the majority of cases are sporadic.
Patients with KID syndrome present with vascularizing
keratitis and hearing loss in conjunction with various skin
manifestations (erythematous lesions, hyperkeratotic pla-
ques, palmoplantar keratoderma, inflammatory nodules),
alopecia and dystrophic nails. Patients also show increased
susceptibility to viral, bacterial and mycotic infections and
some types of skin cancer. Patients with a life-threatening
disease have occasionally been reported. We report here
a new case of KID syndrome with early childhood death
caused by the GJB2 mutation p.Gly12Arg.
CASE REPORT
of 7 years. Psychomotor development and height were normal, but
he was underweight (–1.5 standard deviation (SD)). He presented
severe hyperkeratosis, with areas of hypertrophic and inflamed skin
over the entire body, which was more pronounced on the feet, legs
and mouth. A characteristic “leather grain-like” appearance was
seen on his palms and soles, and his nails were dystrophic (Fig.
1). The skin was foul-smelling and skin surface swabs repeatedly
revealed numerous bacteria (Streptococcus agalactiae, Coryne-
bacterium striatum, Klebsiella pneumoniae, Providencia stuartii,
Citrobacter koseri (Citrobacter diversus), Proteus mirabilis and
Pseudomonas aeruginosa), but no human papilloma virus. A few
months later, his general condition deteriorated, with severe pain,
fever, malnutrition and exacerbation of the skin condition. He was
transferred to the intensive care unit, where he was diagnosed with
septicaemia (Corynebacterium and Staphylococcus aureus). He
was intubated and put on a ventilator. He received rehydration,
transfusions, intravenous antibiotics and antifungal drugs. He died
shortly afterwards from septic shock combined with renal failure.
DISCUSSION
We report here a new case of fatal childhood KID syn-
drome. In the literature, we found 21 other patients (from
19 families) with KID syndrome with a fatal outcome (1–7).
The characteristics of these patients (and our patient) are
reported in Table SI 1 . Of these 21 patients, 19 died in the
neonatal period (before reaching the age of 18 months),
none during late infancy and 2 in early adulthood (death at
The patient was the first child of healthy unrelated parents origina-
ting from Democratic Republic of Congo. He was born at term (37 th
https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3218
week of pregnancy), weighed 2.9 kg and measured 46.5
cm. He has 2 healthy half-sisters. His skin was normal
at birth and the first skin abnormality was noticed at
the age of 2 weeks in the form of generalized hyperke-
ratosis. Bilateral sensorineural hearing loss (negative
evoked oto-acoustic emissions) was diagnosed at the
age of 9 months and warranted hearing aids. Bilateral
keratitis with ulceration and corneal neovasculariza-
tion was diagnosed at 2 years of age. The diagnosis of
KID syndrome was suspected and confirmed by the
sequencing of the GJB2 gene, showing that the patient
was heterozygous for the c.34G>C (p.Gly12Arg) GJB2
mutation. No parental molecular analysis could be
performed. The hyperkeratosis gradually worsened
over time and the clinical course was complicated by
several episodes of fungal and bacterial cutaneous
infections requiring systemic therapy with antibiotics
or antifungal drugs. The patient was started on acitretin
(1 mg/kg/day) at the age of 5 years. This was deemed
ineffective and was discontinued at the age of 7 years.
He was then started on alitretinoin (0.5 mg/kg/day).
Again, this proved ineffective and was stopped after 6
Fig. 1. Massive hyperplasia and hyperkeratosis. On (a) the legs, (b and c)
months. He was first seen in our department at the age
extremities, and (d) umbilicus.
1
This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta
Journal Compilation © 2019 Acta Dermato-Venereologica.
doi: 10.2340/00015555-3218
Acta Derm Venereol 2019; 99: 921–922