The Diagnosis of Infantile FSHD (IFSHD)
Early Onset or Infantile FSHD
FSHD also has a form called Infantile FSHD (IFSHD). IFSHD is a more severe course of` FSHD1A or FSHD1B. What makes the disease more severe has not yet been determined. Hearing loss (high frequency bilateral sensorineural), vision problems (Coats’ Disease and retinal telangiectasias), and seizures have been documented in IFSHD. There is no generally accepted estimate of its incidence, but it is rare.
Dr. O. Brouwer et. al. in the Netherlands defined early onset FSHD (IFSHD) as:
1. Signs or symptoms of facial weakness before age five; and
He identified only six patients who met those criteria, and their phenotypes did not differ significantly from patients with later onset. Only four of the six had documented 4q35 deletions. Brouwer’s population strongly favored familial cases (only 9 of 96 patients studied had sporadic disease).
Jardine, et. al. in the United Kingdom reported that patients with de novo 4q35 deletions tend to have larger deletions than familial cases, and also to have more severe disease. The mean age at onset of this population was 6.8 years, 30% used a wheelchair before 18 years of age, and three had congenital facial diplegia and sensorineural deafness. This age at wheelchair use contrasts sharply with the overall statistics reporting that 20% of FSHD patients require a wheelchair by age 50.
Arahata et. al. in Japan analyzed the data from 78 independent families with 4q35 FSHD. They found that 16-17% of the patients had early onset disease. Approximately one-half of these had EcoRI fragments of less than 11kb, the smallest fragments. All of the patients with these smallest fragments had early onset disease. In Japan 50% of the small fragment group of patients also had epilepsy and almost 90% had mental retardation.
Korf et. al. reported six patients with facial diplegia occurring in the first year. All had severe progressive disability prior to adolescence.
In Deymeer’s Neuromuscular Diseases from Basic Mechanism to Clinical Management, Dr. Lunt writes in his chapter “Facioscapulohumeral muscular dystrophy Diagnostic and Molecular Aspects” that “In more severe infantile onset cases, facial weakness is the earliest and most prominent sign. Thus, the infant may show little or no facial expression, appearing unable to smile, and may be initially misdiagnosed as having Mobius syndrome. Pelvic girdle weakness in the most severe cases can be prominent by age 10 years, leading to consideration of Xp2l or limb girdle types of muscular dystrophy, but unlike these conditions, FSHD is still characterized by an even greater degree of shoulder girdle weakness rather than pelvic weakness. FSHD is inevitably progressive, and an overall 20% of patients require a wheelchair by the fifth decade, although this can be required before age 20 years in many of the most severe new mutation cases."
This might suggest that very early onset FSHD patients are more likely to have de novo mutations and that the clinical manifestations may include congenital facial diplegia, congenital deafness, mental retardation or seizures. These patients are likely to require wheelchairs in childhood.
Some new ideas and emerging definitions and criteria being put forth by researchers working on IFSHD are:
• clinically severe FSHD; patients who report needing a wheelchair greater than 50% of the time by age 18 years; and
• those predicted to have severe FSHD; those patients with EcoRI fragments smaller than 15kb. This is a conservative value and is expected to identify patients with a milder phenotype in addition to the more severe. This corresponds to roughly three or fewer residual 3.3kb repeats.
The online database Online Mendelian Inheritance in Man (OMIM) is an excellent source for further information on the science and medicine of infantile facioscapulohumeral muscular dystrophy. OMIM was designed for use by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. OMIM is developed and maintained by the National Center for Biotechnology Information (NCBI). This database is a catalog of human genes and genetic disorders and has hyperlinks to MEDLINE and sequence records in the Entrez system, and links to additional related resources at NCBI and elsewhere.
To see the Online Mendelian Inheritance in Man pages on infantile facioscapulohumeral muscular dystrophy, Infantile FSHMD please click HERE.
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