(FRAXE syndrome, FRAXF syndrome, Martin Bell syndrome)

It is the most common form of transmissible mental retardation: 1/3700 boys and approximately 1/7000 girls of Caucasian race are heterozygous. Genetic syndrome with complex transmission requiring more than 200 repetitions of the CGG triplet of the FMR1 gene (Fragility Mental Retardation 1) or its hypermethylation at locus Xq27.3. Those 2 abnormalities render the FMR1 gene silent.

Association of a light or mild mental deficit, a hyperactive behavior with attention deficit (and irritability) or an autistic withdrawal behavior (speech delay), learning difficulties and facial dysmorphism (moderate macrocephaly  with a high forehead, a large nose root, dental anomalies, a  prominent lower jaw, prominent ears, an arched palate) . It is difficult to diagnose before puberty. Macroorchidy (increased testicular volume) is observed after puberty in 80 % of cases. A moderate hyperlaxity is common: hypermobility of joints, flat feet, scoliosis, congenital dislocation of the hip. Sometimes, pectus excavatum and mitral valve prolapse.

The premutation of the FMR1 gene (repeat of 50 to 200 CGG triplets) does not cause the syndrome but causes hyperproduction of mRNA leading to the sequestration of neurotropic proteins. This can cause:

• primary ovarian failure: menopause before 40 years of age
• psychiatric disorders: depression and anxiety
• migraines
• hypertension
• ataxia around 60 years of age: FXTAS syndrome (Fragile X- associated Tremor Ataxia Syndrome): cerebellar ataxia with intentional tremor, cognitive decline and hyperintensities of the white matter at MRI. Environmental factors, including general anesthesia (some cases of post-operative cognitive dysfunction), could promote the development of this syndrome.

Anesthetic implications:

behavioral disorder (autism). Epilepsy. Increased risk of obstructive sleep apnea. Echocardiography, especially in case of pectus excavatum.

References:

-         Hersh JH, Saul RA et al. 
Clinical report: health supervision for children with Fragile X syndrome. 
Pediatrics 2011; 127: 994-1006

-        Prottengeier J, Münster T, Pohmer S, Schmidt J. 
Anaesthesia and orphan disease: fragile X syndrome (Martin-Bell syndrome). 
Eur J Anaesthesiol 2015 ; 32 : 2157  

-        Ligsay A, El-Deeb M, Salcedo-Arellano MJ, Schloemerkemper N, Grayson JS, Hagerman R.
General anesthetic use in Fragile X spectrum disorders.
J Neurosurg Anesthesiol 2019; 31:285–90

Updated: December  2022