Name of = speciality

Name of speciality =20 : =20 Pediatrics

Name of case=20 =20 : =20 The floppy neonate-SMA type 1

Name of expert : =20 Dr. Tejinder Singh, Dr. Monika Sharma

Name of Hospital =20 : =20 Christian Medical = College,=20 Ludhiana

=20 A 25 days old female neonate was referred to us with history of = poor=20 activity since birth and respiratory distress, for evaluation of = hypotonia. The=20 baby was born to a second gravid mother at term following an uneventful=20 pregnancy. There was no remarkable history during the antenatal period. = At birth=20 the baby was noted to have a drooping jaw with development of = generalized=20 hypotonia within few hours of birth. A diagnosis of sepsis with = meningitis was=20 entertained. The baby received antibiotics and underwent a neuroimaging = which=20 was normal. The child developed severe pneumonia and had to be = ventilated for=20 respiratory failure for 5 days. The child recovered from the pneumonia, = however=20 sever hypotonia with drolling of saliva persisted. Baby also had = difficulty in=20 breastfeeds and had to be tube fed. In neurologic examination, muscle = mass was=20 decreased, deep tendon reflexes were absent and intermittent tremulous = movements=20 were noted in the tongue and extremities. Apart from these, there were = no other=20 remarkable neurological findings.

Discussions: A meticulously taken history in = a=20 classical case of spinal muscle atrophy may reveal a history of = decreased fetal=20 movements antenatally. The severe infantile form, known as = Werdnig-Hoffmann=20 disease or SMA type 1 may present as a severely hypotonic neonate, with = thin=20 muscle mass, absent reflexes and involvement of the face, tongue and jaw = muscles. The muscles of eye movement and sphincters are unaffected. = Severe=20 hyptonia may result I respiratory distress and difficulty in feeding,=20 fasiculations are a specific clinical sign. Tremors may also be = noted.

=20 A sepsis workup was done revealing gram negative sepsis which = was=20 treated with the sensitive antibiotics. There was no evidence of = meningitis.=20 Neuroimaging was normal. A metabolic profile including blood sugar and = serum=20 calcium were normal. CPK-MB was within normal limits.

=20 Electromyography showed occasional fasciculatins. Nerve = conduction=20 studies showed absent H reflex, indicative of anterior horn cell = disease. Nerve=20 conduction latencies were normal.

Discussions: The serum Ck = levels are=20 generally normal or mildly elevated. Signs of denervation may be = observed in=20 electromyography in form of fibrillation potentials. Electromyogrpahy is = helpful=20 in differentiating central and peripheral forms of myopathies. = Electromyography=20 has high predictive value = for=20 infantile from of spinal muscle atrophy, though may not be so helpful in = myopathy. Some authors were able to accurately diagnose SMA in 65% of = neonates=20 with hypotonia.

=20 Nerve conduction studies shown slowing in motor nerves in later = stages of=20 the disease. Sensory nerve conduction is normal. Significant slowing may = be seen=20 in inherited sensorimotor neuropathies and neurodegenerative diseases. = Normal=20 electro diagnostic studies favor central causes of hypotonia.

Genetic analysis for = SMA consists=20 of detection of homozygous deletion of the 5q11-q13 locus on chromosome = 5,=20 involving the SMN(survivor motor neuron) gene. Another gene, neuronal = apoptosis=20 inhibitory gene(NAIP) is located close to the SMN gene, and may be = involved in=20 some cases of SMA. Molecualr diagnosis of the gene deletions can be done = by=20 polymerase chain reaction(PCR) followed by restriction fragment length=20 polymorphism(RFLP). Detection of the genetic defect can detect up to 95% = cases=20 of SMA.

3. Management : The neonate was managed for = sepsis.=20 Persistent accumulation of saliva necessitated frequent suctioning and = continued=20 oxygen requirement. The baby could not be put to breast and had to be = sent home=20 on tube feeds.

Comment: No definite medial = management=20 is available to prevent progression of the disease. 2/3rds of cases of = SMA type=20 1 die by 2 years of age and many die in early infancy as a result of=20 intercurrent infections. Therapy is supportive, addressing feeding = problems and=20 management of the complicating infections.

4. Other differential = diagnosis :=20 Floppiness or = hypotonia is=20 indicated by increased extensibility and passivity. Hypotonia may be = central or=20 peripheral in origin, and has an exhaustive list of differential = diagnosis. This=20 list include: developmental muscle disorders, such as myotubular = myopathy,=20 congenital muscle fiber disproportion, nemaline rod myopathy; brian=20 malformations such as cerebellar hypoplasia; muscular dystrophies such = as=20 myotonic muscular dystrophy and congential muscular dystrophy. = Endocrinal cases=20 such as hypothyroidism, mitochondrial myopathies and conditions = affecting the=20 transmission pathway of motor impulse can result in hypotonia. Spinal = muscular=20 atrophies are the classical example of the last group, which is caused = by=20 degenerarion of the motor neurons in fetal period. The severe infantile = form may=20 present in the neonatal period., Downs syndrome, Prader Willi syndrome = and=20 infantile autism may also present with hypotonia in early infancy. = Transient=20 hypotonia in a neonate may be noted with metabolic derangements such as=20 hypoglycemia, hypocalcemia, with meningitis, intracranial bleeds, = hydroephalus=20 and cenral hypoxia, These commoner causes are easy to exclude. Though an = algorithmic diagnosis may not always be available, detailed history = followed by=20 clinical examination and appropriate investigations is the key to = identifying=20 the cause.

5. Recent Advances : = Molecular genetic studies have = given rise=20 to the exciting possibilities of newer drugn treatments for SMA current=20 strategies modulate the genetic machinery to increase production of SMN = protein=20 from the genes.

=20 Recently, sodium butyrate has been found to increase the = production of=20 this protein in mouse tissue culture. Use of this chemical in humans is=20 presently a subject a research.

6. Genetic Counseling : = Risk of recurrence can be = predicted after=20 the genetic confirmation of the diagnosis. The risk of recurrence in = subsequent=20 pregnancies is 25% in autosomal recessive cases.

1. Sarnat HB. In Neuromusculr = disorders. Chp 603.2 Spinal Muscular Atrophies. In

Nelson=20 Textbook of Pediatrics. 17th edition. Editors Behrman RE, Kleigman RM, = Jenson=20 HB. Pg. 2075-76.

2. Russel JW, Afifi AK, Ross = MA.=20 Predictive value of electromyography in diagnosis

and prognosis of = the=20 hypotonic infant. J Child Neurol. 1992 Oct; 7(4):387-91

3. Renault F. The role of=20 electodiagnostic studies in the diagnosis of hypotonia in

4. Panigrahi I, Kesari A, = Phadke SR,=20 Mittal B. Clinical and molecular diagnosis of