Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1)

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare inherited disorder characterized by distal muscle weakness and respiratory failure. It is caused by mutations in the IGHMBP2 gene located on chromosome 11q13.2 (Grohmann et al., 2001) and is clinically and genetically distinct from classic spinal muscular atrophy type 1 (SMA). At birth, infants with SMARD1 are often noted to have a weak cry, inspiratory stridor, feeding difficulties, and congenital contractures, especially foot deformities. Intrauterine growth retardation, premature birth, and a history of decreased fetal movements are also common. Infants with SMARD1 typically develop progressive, severe respiratory distress within the first six weeks to six months of life, resulting in the need for irreversible mechanical ventilation (Grohmann et al., 2001; Guenther et al., 2007); however, several patients have been reported with juvenile onset of respiratory distress (Guenther et al., 2004; Guenther et al., 2009). The respiratory distress is due to diaphragmatic paralysis (diaphragmatic hernia observed on chest X-ray). As the disease progresses, autonomic dysfunction and tongue twitching develop, and deep tendon reflexes are absent. Electrophysiologic examinations may reveal reduced motor nerve conduction velocities. Ultrastructural studies may identify axonal and motor end-plate degeneration, and abnormal myelin formation (Kaindl et al., 2008; Diers et al., 2005). The muscle weakness caused by SMARD1 eventually leads to complete paralysis. Intelligence is not affected.

Tests Available

Forms and Documents

Test Details

IGHMBP2
  • Confirmation of the clinical diagnosis
  • Identification of at-risk family members
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

342
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 518.83 Chronic respiratory failure
  • 519.4 Disorders of diaphragm Diaphragmitis, Paralysis of diaphragm Relaxation of diaphragm
  • 335.1 Spinal muscular atrophy
* For price inquiries please email zebras@genedx.com

References

  1. Grohmann et al., (2001) Nat Genet 29:75-77
  2. Guenther et al., (2007) Hum Mutat 28:808-815
  3. Guenther et al., (2004) Hum Genet 115:319-326
  4. Guenther et al., (2009) J Mol Med 87:31-41
  5. Kaindl et al., (2008) J Child Neurol 23:199-204
  6. Diers et al., (2005) Acta Neuropathol 110:289-297
  7. Grohmann et al., (2003) Ann Neurol 54:719-724
  8. Basel-Vanagaite et al., (2008) Genet Testing 12:53-56

Forms and Documents

Test Details

AARS, ATL1, ATP7A, BSCL2, DNAJB2, DNM2, DNMT1, DYNC1H1, EGR2, FAM134B, FGD4, FIG4, GAN, GARS, GDAP1, GJB1, GLA, HINT1, HSPB1, HSPB8, IGHMBP2, IKBKAP, INF2, KIF1A, KIF5A, LITAF, LMNA, LRSAM1, MFN2, MPZ, MTMR2, NDRG1, NEFL, NGF, NTRK1, PLEKHG5, PMP22, PRPS1, PRX, RAB7A, REEP1 (C2ORF23), SBF2, SCN9A, SH3TC2, SLC12A6, SLC52A2, SPTLC1, SPTLC2, TFG, TRPV4, TTR, WNK1, YARS
  • Molecular confirmation of a clinical diagnosis
  • To assist with decisions about treatment and management of individuals with neuropathy
  • Testing of at-risk relatives for specific known mutation(s) previously identified in an affected family member
  • Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

737
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81325x1, 81404x1, 81405x4, 81406x4
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

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