[MIM 305 000, 127 550, 224 230]

(Zinsser-Cole-Ebert syndrome)

Rare. Association of anomalies of the skin and mucous membranes to medullary aplasia (90% of cases). Variable transmission mode: X-linked, autosomal dominant or recessive and numerous sporadic cases. Mutation of one of the genes involved in the maintenance of  thetelomeres (= long sequence of DNA with repeats of nucleotides associated to proteinic complexes, such as the telomerase or Sheltrin complex, located at the end of each chromosome). These telomeres shorten at the end of each cell division and are repaired by these proteinic complexes. The genes are TERT, TERC, DKC1 (X), NOLA2, NOLA3 and TINF2 (AD).

Clinical presentation varies with a median age of diagnosis at age 15 years:

-        diagnostic triad known as 'classic':  reticulated cutaneous pigmentation (face, neck, chest), leukoplakia of the mucous membranes (mostly oral, but sometimes conjunctival, genital, anal) and dystrophy of the nails ( flat, atrophic and longitudinally striated nails). Median age of onset: 6 to 8 years

-         nasolacrimal duct obstruction, sometimes: blepharitis, conjunctivitis, ectropion

-         premature falling of  teeth and caries

-         restrictive pulmonary syndrome (20%) due to progressive pulmonary fibrosis

-         sometimes: cirrhosis with or without portal hypertension, hepatopulmonary syndrome, osteoporosis, cardiomyopathy

-         hematologic involvement: cytopenia in 93 % of cases (median: 10 years); aplastic anemia of childhood or early adulthood; risk of malignant hemopathy (leukemia, Hodgkin)

-         major risk of solid tumours (squamous cell) of the oral cavity, in the head and neck region, anogenital or digestive tract.

Particular and very severe forms with early onset :

• Hoyeraal-Hreidarsson syndrome: onset before the age of one year: cerebellar hypoplasia, microcephaly and psychomotor retardation with intrauterine growth retardation and medullary aplasia. Mutation of the DKC1, TINF2, RTEL1 or TERT genes.
• Revesz syndrome : in young children: medullary aplasia and bilateral exudative retinopathy; sometimes: delayed intrauterine growth, cerebral calcifications; adult: pulmonary fibrosis, isolated cirrhosis, cancer. Mutation of the TERC, TINF2 or TERT genes.

Medullary impairment may be treated with a bone marrow transplantation (ideally with family donor). Conditioning must be reduced to avoid complications such as pulmonary fibrosis or veno-occlusive disease of the liver. The risk of digestive bleeding persists even after a successful transplantation.

Anesthetic implications: 

check blood count, lung function and chest XRay; risk of pulmonary hypertension and of esophageal stenosis  ("full esophagus"?); risk of digestive bleeding; esophageal varices, antral vascular dysplasia, vascular and erythematous dysplastic lesions of the small bowel; fragile teeth; strict asepsis

References : 

-        Mialou V, Leblanc T, Peffault de Latour R, Dalle J-H, Socié G. 
La dyskératose congénitale : mise au point. 
Arch Pédiatr 2013 ; 20 : 299-306.

-        Mitre CI, Corda DM, Dunca F, Iancu C. 
Anesthesia in a patient with dyskeratosis congenita presenting for urgent subtotal gastrectomy. 
J Clin Anesth 2015; 27:612-615 

-        Himes RW, Chiou EH, Queliza K, Shouval DS, Somech R et al.
Gastrointestinal hemorrhage : a manifestation of the telomere biology disorders.
J Pediatr 2021; 230: 55-61.

Updated: August 2021