Severe phenotype in infantile facioscapulohumeral muscular dystrophy

While much is known about the clinical course of adult FSHD, the third most common inherited muscular dystrophy, data on the "infantile phenotype" and especially on the progression of the disease in children are limited. We have followed a cohort of 7 patients with infantile FSHD for 9-25 years and here report the clinical and genetic findings in this group. Infantile FSHD is relatively rare, amounting to 4% of all of our FSHD patients. Despite some variability in the progression, infantile FSHD has a more consistent phenotype than adult FSHD. Although they had normal motor milestones, all patients showed facial weakness from early childhood, and subsequently were severely affected with rapid progression of the disease, marked muscular wasting, weakness, and hyperlordosis. None of the patients have shown signs of nocturnal hypoventilation or cardiomyopathy so far. No correlation was found between sex and the severity of phenotype whereas all but one patient had very short fragment sizes of the D4Z4 repeat. Only two patients had a de novo mutation: 3 patients inherited the mutation from a parent with somatic mosaicism, and one was inherited from a parent with classical adult FSHD. One patient was unusual in having one allele inherited from his father who showed somatic mosaicism and one allele with an additional de novo mutation. We conclude that infantile FSHD is a severe and rapidly progressive disease, and this needs to be taken into account in the advice given to patients diagnosed in early childhood. However, our data also suggest that the risk to an individual with classical FSHD of having a child with the infantile form is low.