spinal muscular atrophy ( sma ) is a neuromuscular disorder characterized by degeneration of the -motor neurons , leading to symmetrical muscle weakness and atrophy mainly of the lower limbs 1 . here
, we report on an infant with sma type 1 with a rare compound heterozygosity of the survival of motor neuron 1 gene ( smn1 ) and characteristic fasciculations of the tongue .
a 4-month old , caucasian boy with an unremarkable antenatal history ( first child of nonconsanguineous , healthy parents , no polyhydramnios ) was admitted to our hospital due to dyscataposia and mucus congestion with suspicion of a pulmonary infection .
a mild muscular hypotonia was observed by the family 's pediatrician during standard examinations by age 1  month .
our examination revealed a poor sucking reflex , failure to thrive , proximal and peripheral muscular weakness with a bell - shaped chest and arreflexia .
lower limbs were more strongly affected than upper limbs . on inspection , fasciculations of the tongue were observed 
most prominently at the periphery of the tongue ( video s1 ) . magnetic resonance imaging ( mri ) of the brain showed a mega - cisterna magna ( mcm , fig.1 ) . during hospitalization ,
molecular genetic testing showed a rare compound heterozygosity for a point mutation c.815a > g ( p.y272c ) in exon 6 of the smn1 gene ( omim 600354 ) on the paternal allele and a deletion of smn1 exon 7 and 8 on the maternal allele , in the presence of two copies of the smn2 gene ( omim 601627 ) confirming the diagnosis of sma . at parental request
spinal muscular atrophy is a heterogeneous neuromuscular disorder and the second most common lethal , autosomal recessive disease in caucasians after cystic fibrosis 2 .
three clinical subtypes depending on age of clinical onset and maximum motor function have been identified 1 .
type 1 ( werdnig - hoffmann , omim 253300 )  the most severe and common type of sma  has an early onset and progressive unrelenting course resulting in death due to respiratory insufficiency within the first 2  years 2 .
characteristic clinical features include profound hypotonia , symmetrical paralysis , little or no head control and areflexia 1,3 .
fasciculations and atrophy of the tongue affect roughly one - third to one - half of patients with sma , and may be noted during the first months of life , as in our patient 3 .
fasciculations of the tongue may also be seen in neonates with other medical conditions such as hypoxic - ischemic injury ( hie ) , mobius syndrome , and storage disorders ( pompe disease ) 3 .
usually , these distinct clinical entities can be differentiated from sma by taking a detailed birth history ( e.g. , for hie ) or taking into account other characteristic clinical findings ( e.g. , macroglossia in pompe disease ) .
in addition to tongue involvement , fasciculation of the eyelids may also be seen in children with sma .
several studies in infants have found an association between cerebrospinal fluid space abnormalities such as ventricular dilatation and congenital myotonic dystrophies 4 ; such abnormalities , like dilatation of the cisterna observed in our patient , may not result in serious complications and remain in most of the cases uninvestigated .
mcm is a controversial entity which is generally thought to be an anatomic variant with no clinical significance but may constitute part of several malformation syndromes such as dandy walker complex ( dwc ) . to the best of our knowledge , there is only one reported association between sma type i and blake 's pouch cyst , which along with mcm is regarded as a less severe malformation included in the dwc 5 .
the vast majority of patients display a homozygous absence of smn1 exons 7 or 8 or exon 7 only , whereas only a few ( approximately 4% ) show compound heterozygosity for a point mutation on one and a deletion on the other chromosome 2 .
unfortunately , in patients who do not present a homozygous disruption of the smn1 gene , adversities in terms of diagnosis , prognosis and genetic counseling still occur .
c.815a > g ( p.y272c ) , a missense mutation in a highly conserved region in exon 6 of smn1 
 68 , accounts for approximately 20% of sma patients with compound heterozygosity for a point mutation 2,6 .
p.y272c is found to result in almost complete reduction in the self - oligomerization capacity 9 , which suggests it to be a severe mutation8 and is in agreement with our case . in conclusion ,
muscular hypotonia is a common clinical sign in infants and may be associated with several conditions including neuromuscular disorders , connective tissue disorders , metabolic diseases , or even prematurity .
the presence of tongue fasciculations , although not pathognomonic , and in combination with a thorough history , may be suggestive of sma diagnosis .
additional supporting information may be found in the online version of this article : video s1 .
 key clinical messagemuscular hypotonia in infants may be associated with several conditions , such as spinal muscular atrophy ( sma ) . 
 we report on an infant with tongue fasciculations and a rare mutation of the smn1 gene . 
 the presence of tongue fasciculations in combination with a thorough history may be suggestive of sma . 
Introduction
Case Report
Discussion
Conflict of Interest
Supporting Information