myocardial remodeling, and cardiac conduction disturbances were not present. Other possible causes of cardiac dysfunction include peripartum cardiomyopathy and viral myocarditis. However, diagnostic criteria were not fulfilled for either of these differential diagnoses.7 Respiratory muscle involvement may have contributed to the clinical presentation, particularly because other symptoms of cardiac failure were subtle and results of pulmonary function tests during early pregnancy revealed moderate restrictive lung function. Familial predisposition, although unlikely, cannot be ruled out because the patient’s mother had myocarditis with transient conduction abnormalities at the age of 37 years, her maternal grandmother had died of cardiac insufficiency, and her maternal great-grandmother had died unexpectedly at the age of 62 years. Myocardial biopsy was not performed because of normal electrocardiogram results, absent signs of infection, and excellent and immediate recovery after delivery. In conclusion, we report a patient with progressive and transient cardiac dysfunction with Bethlem myopathy during pregnancy. We assume this finding to be related to the underlying myopathy rather than viral or obstetric causes. Therefore, we recommend close monitoring of these patients during pregnancy
because of the increased myocardial preload during pregnancy, which may unmask or worsen a hitherto subclinical myocardial disorder.
Obstetric Outcome in a Primigravid Patient With Autosomal-Recessive Multiminicore Myopathy
patients. Little is known about pregnancy outcomes, although patients with other neuromuscular disorders may experience a postpartum decline.
Caitlyn Klaska, BS, and Bernard Gonik,
MD
BACKGROUND: Multiminicore disease is a congenital myopathy characterized by muscle weakness and respiratory impairment. Predilection for the development of malignant hyperthermia has been reported in select
REFERENCES 1. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification. Eur J Echocardiogr 2006;7:79–108. 2. McClain PE. Characterisation of cardiac muscle collagen: molecular heterogeneity. J Biol Chem 1974;249:2303–11. 3. de Visser M, de Voogt WG, la Rivière GV. The heart in Becker muscular dystrophy, facioscapulohumeral dystrophy, and Bethlem myopathy. Muscle Nerve 1992;15:591–6. 4. van der Kooi AJ, de Voogt WG, Bertini E, Merlini L, Talim FB, Ben Yaou R, et al. Cardiac and pulmonary investigations in Bethlem myopathy. Arch Neurol 2006;63:1617–21. 5. Finsterer J, Stöllberger C. Cardiac involvement in Bethlem myopathy. Arch Neurol 2007;64:916. 6. Pepe G, Bertini E, Bonaldo P, Bushby K, Giusti B, de Visser M, et al. Bethlem myopathy (BETHLEM) and Ullrich scleroatonic muscular dystrophy: 100th ENMC international workshop, 2324 November 2001, Naarden, the Netherlands. Neuromuscul Disord 2002;12:984–93. 7. Johnson-Coyle L, Jensen L, Sobey A. Peripartum cardiomyopathy: review and practice guidelines. Am J Crit Care 2012;21:89–98. 8. Savu O, Jurcut R, Giusca S, van Mieghem T, Gussi I, Popescu BA, et al. Morphological and functional adaptation of the maternal heart during pregnancy. Circ Cardiovasc Imaging 2012;5:289–97.
CASE: We report a case of pregnancy associated with autosomal-recessive multiminicore disease. Genetic implications of this condition were addressed. Orthopedic complications were managed through physical medicine and rehabilitation consultation. Under epidural anesthesia, a healthy full-term neonate was delivered through spontaneous vaginal delivery. There was no evidence of malignant hyperthermia or functional decline in the puerperium. CONCLUSION: A successful pregnancy outcome was achieved in a patient with multiminicore myopathy by proactively addressing potential genetic, orthopedic, and anesthetic concerns associated with this condition.
From the Wayne State University School of Medicine and the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan.
(Obstet Gynecol 2014;123:438–40)
Corresponding author: Bernard Gonik, MD, 6071 West Outer Drive, Suite M541, Detroit, MI 48235; e-mail: [email protected].
ultiminicore disease is a congenital core myopathy. Classic multiminicore disease is associated with recessive mutations in the selenoprotein N gene (SEPN1) and is characterized by respiratory impairment.1 Other phenotypic variants of multiminicore disease are associated with recessive or dominant mutations
Financial Disclosure The authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
438
Klaska and Gonik
DOI: 10.1097/AOG.0000000000000003
M
Multiminicore Disease in Pregnancy
OBSTETRICS & GYNECOLOGY
Table 1. Genetic Variants in a Case of AutosomalRecessive Multiminicore Disease
Family member Unaffected father Unaffected mother Proband Affected sibling 1 Unaffected sibling 1 2 3 4 5 6 7 8 9
RYR1 p. M4881T
RYR1 p. E1643K+p. C3733Y
+ 2 + +
2 + + +
2 2 2 2 2 + 2 + 2
+ + 2 2 2 2 2 2 +
COMMENT
in the skeletal muscle ryanodine receptor gene (RYR1).1 Interestingly, RYR1 is linked to a trait conferring increased susceptibility to malignant hyperthermia.1 A PubMed search (multi+minicore+disease+myopathy+pregnancy) did not reveal any previously recorded cases of pregnancy in a patient with autosomal-recessive RYR1-linked multiminicore disease. Through this case and the following discussion, we present our suggestions for genetic, orthopedic, anesthetic, and obstetric management in a gravid patient with this condition.
CASE A 25-year-old Caucasian woman of Ashkenazi and Sephardi descent, gravida 1 para 0, presented for her first prenatal visit at 17 weeks of gestation. Her medical history was significant for congenital multiminicore disease diagnosed by skeletal muscle biopsy and genetic studies. Genetic investigations (Table 1) revealed clinically relevant variants in RYR1 suggestive of an autosomal-recessive inheritance pattern. She has undergone multiple surgeries to address complications of her condition, including temporary fundoplication, gastrostomy placement, traumatic hip fracture pinning, and contracture release through Achilles tenotomy. The patient completed both undergraduate and postgraduate degrees. On physical examination, she was found to be 4 feet 7 inches tall and weighed 91 pounds; body mass index (calculated as weight (kg)/[height (m)]2) was 21.1. The remainder of the examination was unremarkable apart from a waddling gait, scoliosis, and borderline clinical pelvimetry. Pulmonary function studies were within normal limits as was a baseline creatine phosphokinase level. The father of the neonate had been tested previously for the known variants in RYR1 and found to be negative. Fetal diagnostic testing was declined after genetic counseling.
VOL. 123, NO. 2 PART 2, FEBRUARY 2014
The patient noted ankle instability and difficulty with ambulation as the pregnancy progressed. The physical medicine and rehabilitation department was consulted, and lower extremity splinting was offered as treatment. Anesthesia consultation was obtained before the delivery. The patient had spontaneous onset of labor at term. Under epidural anesthesia, she delivered a 3,065-g (6 pounds 12 ounces) healthy boy through spontaneous vaginal delivery. A coccygeal fracture was suspected clinically; however, no diagnostic studies were performed. At 6 weeks postpartum, the patient was breast feeding and showed no evidence of disease progression.
The rarity of multiminicore disease necessitates that specific antenatal and intrapartum issues be addressed. In this case, a genetic pedigree (Table 1) was previously completed that demonstrated autosomal-recessive inheritance. Testing of the partner confirmed absence of the patient’s RYR1 variants. Prenatal diagnosis through DNA analysis from chorionic villus sampling or amniocentesis would be considered if the disease-causing RYR1 variants had been identified in both the proband and her partner. Without genetic testing, secondtrimester ultrasonography demonstrating absence of fetal movement, polyhydramnios, or absence of fetal movement and polyhydramnios in a gravida with multiminicore disease should raise suspicion for fetal involvement. A fetal akinesia syndrome has been associated with central core disease, which is also a congenital myopathy linked to variants in RYR1.2 The known physiologic changes that occur in pregnancy should be anticipated to have a compromising effect on gravidas with congenital myopathies. Patients with multiminicore disease exhibit a spectrum of phenotypes depending on the disease-causing lesion. In general, the condition is slowly or nonprogressive with a tendency to present early in life with delayed motor development.1 Axial and proximal muscle weakness is prominent.1 Respiratory impairment is a feature in classic multiminicore disease, although it is typically milder in RYR1related disease such as that found in our patient.1 On an empiric basis, spirometry should be considered in patients with multiminicore disease. The baseline forced vital capacity should be 1 L or greater. Pulmonology consultation should follow if an abnormality is identified or if the patient exhibits symptoms of respiratory compromise. Right-sided heart failure can develop secondary to severe lung disease; therefore, it is important to perform a detailed cardiac examination and proceed with additional testing as indicated.
Klaska and Gonik
Multiminicore Disease in Pregnancy 439
Musculoskeletal symptoms in pregnant patients with multiminicore disease should be monitored throughout gestation. Consultation with a physical medicine and rehabilitation specialist can help prepare these patients for labor with core-strengthening exercises that target the weak trunk flexors. Although the first stage of labor primarily involves smooth muscle that is unaffected by multiminicore disease, the maternal abdominal muscles contribute significantly to the second stage of labor. Additionally, supervised muscle strengthening can help prevent muscle breakdown, which is important because these patients are unable to rebuild muscle. We empirically obtained a baseline creatine phosphokinase level to act as a marker of potential muscle injury. Physical medicine and rehabilitation can also suggest support appliances for orthopedic symptoms. Our patient required an Achilles tendon boot as she gained weight and experienced changes in her body mechanics. Of interest, a study in pediatric patients with core myopathies demonstrated significant increases in muscle strength and forced vital capacity after 6 months of salbutamol administration.3 Because this class of drug is used in obstetrics, there may be an opportunity to examine similar agents in pregnant patients diagnosed with multiminicore disease. In addition to its etiologic role in some forms of multiminicore disease, RYR1 is associated with an increased risk of malignant hyperthermia in the heterozygous state.1 SEPN1-related multiminicore disease has no known association with malignant hyperthermia.1 Therefore, establishing the specific genetic abnormality in a gravid patient with multiminicore disease through DNA sequencing is important. It is also possible to do in vitro assays to assess malignant hyperthermia risk. An anesthesiologist can ensure that precautions such as avoidance of volatile inhaled anesthetics and depolarizing muscle relaxants are implemented. Early placement of an epidural catheter for delivery of local anesthesia is an acceptable approach to pain relief in the laboring patient with multiminicore disease. Optimal choice of anesthetic is unclear, although one report suggested ropivacaine may have advantages over bupivacaine in patients with muscle weakness.4 Several other considerations in obstetric management apply to gravidas with multiminicore disease. Because they may present with bony pelvis abnormalities, an assessment of clinical pelvimetry is warranted. If the pelvic dimensions suggest compromise such as in our patient, intrapartum monitoring for cephalopelvic disproportion or proceeding to cesarean delivery
440
Klaska and Gonik
should be considered. Magnesium sulfate, an agent often used in cases of preeclampsia, is contraindicated in these patients as a result of effects on respiratory and motor function. Patients should also be made aware of the possibility of earlier operative vaginal delivery if fatigue of the trunk flexors is limiting. Despite the paucity of data addressing pregnancy outcomes in multiminicore disease, it is not possible to draw firm conclusions based on a single case study. A case report by Osada et al5 described a pregnant patient with suspected autosomal-dominant multiminicore disease. However, this case lacked definitive genetic diagnosis and management recommendations primarily focused on anesthetic concerns. Examining other congenital myopathies, both Awater and RudnikSchoneborn et al6,7 demonstrated minimal increased risk for adverse outcomes or operative deliveries compared with the general population. However, Rudnik-Schoneborn et al7 did infer that women with neuromuscular disease who were severely underweight as a result of limited muscle mass were at higher risk for preterm delivery. Rudnik-Schoneborn et al7 also found that patients with earlier onset of their congenital myopathy tended to observe a worsening of symptoms after delivery. Given the lack of data specific to multiminicore disease, it would be prudent to include counseling regarding the possibility of disease progression and irreversible postpartum handicap. REFERENCES 1. Jungbluth H. Multi-minicore disease. Orphanet J Rare Dis 2007; 2:31. 2. Romero NB, Monnier N, Viollet L, Cortey A, Chevallay M, Leroy JP, et al. Dominant and recessive central core disease associated with RYR1 mutations and fetal akinesia. Brain 2003; 126:2341–9. 3. Messina A, Hartley L, Main M, Kinali M, Jungbluth H, Muntoni F, et al. Pilot trial of salbutamol in central core and multi-minicore diseases. Neuropediatrics 2004;35: 262–6. 4. Saito O, Yamamoto T, Mizuno Y. Epidural anesthetic management using ropivacaine in a parturient with multi-minicore disease and susceptibility to malignant hyperthermia. J Anesth 2007;21:113. 5. Osada H, Masuda K, Seki K, Sekiya S. Multi-minicore disease with susceptibility to malignant hyperthermia in pregnancy. Gynecol Obstet Invest 2004;58:32–5. 6. Awater C, Zerres K, Rudnik-Schoneborn S. Pregnancy course and outcome in women with hereditary neuromuscular disorders: comparison of obstetric risks in 178 patients. Eur J Obstet Gynecol Reprod Biol 2012;162:153–9. 7. Rudnik-Schoneborn S, Glauner B, Rohrig D, Zerres K. Obstetric aspects in women with facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, and congenital myopathies. Arch Neurol 1997;54:888–94.
Multiminicore Disease in Pregnancy
OBSTETRICS & GYNECOLOGY
because of the increased myocardial preload during pregnancy, which may unmask or worsen a hitherto subclinical myocardial disorder.
Obstetric Outcome in a Primigravid Patient With Autosomal-Recessive Multiminicore Myopathy
patients. Little is known about pregnancy outcomes, although patients with other neuromuscular disorders may experience a postpartum decline.
Caitlyn Klaska, BS, and Bernard Gonik,
MD
BACKGROUND: Multiminicore disease is a congenital myopathy characterized by muscle weakness and respiratory impairment. Predilection for the development of malignant hyperthermia has been reported in select
REFERENCES 1. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification. Eur J Echocardiogr 2006;7:79–108. 2. McClain PE. Characterisation of cardiac muscle collagen: molecular heterogeneity. J Biol Chem 1974;249:2303–11. 3. de Visser M, de Voogt WG, la Rivière GV. The heart in Becker muscular dystrophy, facioscapulohumeral dystrophy, and Bethlem myopathy. Muscle Nerve 1992;15:591–6. 4. van der Kooi AJ, de Voogt WG, Bertini E, Merlini L, Talim FB, Ben Yaou R, et al. Cardiac and pulmonary investigations in Bethlem myopathy. Arch Neurol 2006;63:1617–21. 5. Finsterer J, Stöllberger C. Cardiac involvement in Bethlem myopathy. Arch Neurol 2007;64:916. 6. Pepe G, Bertini E, Bonaldo P, Bushby K, Giusti B, de Visser M, et al. Bethlem myopathy (BETHLEM) and Ullrich scleroatonic muscular dystrophy: 100th ENMC international workshop, 2324 November 2001, Naarden, the Netherlands. Neuromuscul Disord 2002;12:984–93. 7. Johnson-Coyle L, Jensen L, Sobey A. Peripartum cardiomyopathy: review and practice guidelines. Am J Crit Care 2012;21:89–98. 8. Savu O, Jurcut R, Giusca S, van Mieghem T, Gussi I, Popescu BA, et al. Morphological and functional adaptation of the maternal heart during pregnancy. Circ Cardiovasc Imaging 2012;5:289–97.
CASE: We report a case of pregnancy associated with autosomal-recessive multiminicore disease. Genetic implications of this condition were addressed. Orthopedic complications were managed through physical medicine and rehabilitation consultation. Under epidural anesthesia, a healthy full-term neonate was delivered through spontaneous vaginal delivery. There was no evidence of malignant hyperthermia or functional decline in the puerperium. CONCLUSION: A successful pregnancy outcome was achieved in a patient with multiminicore myopathy by proactively addressing potential genetic, orthopedic, and anesthetic concerns associated with this condition.
From the Wayne State University School of Medicine and the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan.
(Obstet Gynecol 2014;123:438–40)
Corresponding author: Bernard Gonik, MD, 6071 West Outer Drive, Suite M541, Detroit, MI 48235; e-mail: [email protected].
ultiminicore disease is a congenital core myopathy. Classic multiminicore disease is associated with recessive mutations in the selenoprotein N gene (SEPN1) and is characterized by respiratory impairment.1 Other phenotypic variants of multiminicore disease are associated with recessive or dominant mutations
Financial Disclosure The authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
438
Klaska and Gonik
DOI: 10.1097/AOG.0000000000000003
M
Multiminicore Disease in Pregnancy
OBSTETRICS & GYNECOLOGY
Table 1. Genetic Variants in a Case of AutosomalRecessive Multiminicore Disease
Family member Unaffected father Unaffected mother Proband Affected sibling 1 Unaffected sibling 1 2 3 4 5 6 7 8 9
RYR1 p. M4881T
RYR1 p. E1643K+p. C3733Y
+ 2 + +
2 + + +
2 2 2 2 2 + 2 + 2
+ + 2 2 2 2 2 2 +
COMMENT
in the skeletal muscle ryanodine receptor gene (RYR1).1 Interestingly, RYR1 is linked to a trait conferring increased susceptibility to malignant hyperthermia.1 A PubMed search (multi+minicore+disease+myopathy+pregnancy) did not reveal any previously recorded cases of pregnancy in a patient with autosomal-recessive RYR1-linked multiminicore disease. Through this case and the following discussion, we present our suggestions for genetic, orthopedic, anesthetic, and obstetric management in a gravid patient with this condition.
CASE A 25-year-old Caucasian woman of Ashkenazi and Sephardi descent, gravida 1 para 0, presented for her first prenatal visit at 17 weeks of gestation. Her medical history was significant for congenital multiminicore disease diagnosed by skeletal muscle biopsy and genetic studies. Genetic investigations (Table 1) revealed clinically relevant variants in RYR1 suggestive of an autosomal-recessive inheritance pattern. She has undergone multiple surgeries to address complications of her condition, including temporary fundoplication, gastrostomy placement, traumatic hip fracture pinning, and contracture release through Achilles tenotomy. The patient completed both undergraduate and postgraduate degrees. On physical examination, she was found to be 4 feet 7 inches tall and weighed 91 pounds; body mass index (calculated as weight (kg)/[height (m)]2) was 21.1. The remainder of the examination was unremarkable apart from a waddling gait, scoliosis, and borderline clinical pelvimetry. Pulmonary function studies were within normal limits as was a baseline creatine phosphokinase level. The father of the neonate had been tested previously for the known variants in RYR1 and found to be negative. Fetal diagnostic testing was declined after genetic counseling.
VOL. 123, NO. 2 PART 2, FEBRUARY 2014
The patient noted ankle instability and difficulty with ambulation as the pregnancy progressed. The physical medicine and rehabilitation department was consulted, and lower extremity splinting was offered as treatment. Anesthesia consultation was obtained before the delivery. The patient had spontaneous onset of labor at term. Under epidural anesthesia, she delivered a 3,065-g (6 pounds 12 ounces) healthy boy through spontaneous vaginal delivery. A coccygeal fracture was suspected clinically; however, no diagnostic studies were performed. At 6 weeks postpartum, the patient was breast feeding and showed no evidence of disease progression.
The rarity of multiminicore disease necessitates that specific antenatal and intrapartum issues be addressed. In this case, a genetic pedigree (Table 1) was previously completed that demonstrated autosomal-recessive inheritance. Testing of the partner confirmed absence of the patient’s RYR1 variants. Prenatal diagnosis through DNA analysis from chorionic villus sampling or amniocentesis would be considered if the disease-causing RYR1 variants had been identified in both the proband and her partner. Without genetic testing, secondtrimester ultrasonography demonstrating absence of fetal movement, polyhydramnios, or absence of fetal movement and polyhydramnios in a gravida with multiminicore disease should raise suspicion for fetal involvement. A fetal akinesia syndrome has been associated with central core disease, which is also a congenital myopathy linked to variants in RYR1.2 The known physiologic changes that occur in pregnancy should be anticipated to have a compromising effect on gravidas with congenital myopathies. Patients with multiminicore disease exhibit a spectrum of phenotypes depending on the disease-causing lesion. In general, the condition is slowly or nonprogressive with a tendency to present early in life with delayed motor development.1 Axial and proximal muscle weakness is prominent.1 Respiratory impairment is a feature in classic multiminicore disease, although it is typically milder in RYR1related disease such as that found in our patient.1 On an empiric basis, spirometry should be considered in patients with multiminicore disease. The baseline forced vital capacity should be 1 L or greater. Pulmonology consultation should follow if an abnormality is identified or if the patient exhibits symptoms of respiratory compromise. Right-sided heart failure can develop secondary to severe lung disease; therefore, it is important to perform a detailed cardiac examination and proceed with additional testing as indicated.
Klaska and Gonik
Multiminicore Disease in Pregnancy 439
Musculoskeletal symptoms in pregnant patients with multiminicore disease should be monitored throughout gestation. Consultation with a physical medicine and rehabilitation specialist can help prepare these patients for labor with core-strengthening exercises that target the weak trunk flexors. Although the first stage of labor primarily involves smooth muscle that is unaffected by multiminicore disease, the maternal abdominal muscles contribute significantly to the second stage of labor. Additionally, supervised muscle strengthening can help prevent muscle breakdown, which is important because these patients are unable to rebuild muscle. We empirically obtained a baseline creatine phosphokinase level to act as a marker of potential muscle injury. Physical medicine and rehabilitation can also suggest support appliances for orthopedic symptoms. Our patient required an Achilles tendon boot as she gained weight and experienced changes in her body mechanics. Of interest, a study in pediatric patients with core myopathies demonstrated significant increases in muscle strength and forced vital capacity after 6 months of salbutamol administration.3 Because this class of drug is used in obstetrics, there may be an opportunity to examine similar agents in pregnant patients diagnosed with multiminicore disease. In addition to its etiologic role in some forms of multiminicore disease, RYR1 is associated with an increased risk of malignant hyperthermia in the heterozygous state.1 SEPN1-related multiminicore disease has no known association with malignant hyperthermia.1 Therefore, establishing the specific genetic abnormality in a gravid patient with multiminicore disease through DNA sequencing is important. It is also possible to do in vitro assays to assess malignant hyperthermia risk. An anesthesiologist can ensure that precautions such as avoidance of volatile inhaled anesthetics and depolarizing muscle relaxants are implemented. Early placement of an epidural catheter for delivery of local anesthesia is an acceptable approach to pain relief in the laboring patient with multiminicore disease. Optimal choice of anesthetic is unclear, although one report suggested ropivacaine may have advantages over bupivacaine in patients with muscle weakness.4 Several other considerations in obstetric management apply to gravidas with multiminicore disease. Because they may present with bony pelvis abnormalities, an assessment of clinical pelvimetry is warranted. If the pelvic dimensions suggest compromise such as in our patient, intrapartum monitoring for cephalopelvic disproportion or proceeding to cesarean delivery
440
Klaska and Gonik
should be considered. Magnesium sulfate, an agent often used in cases of preeclampsia, is contraindicated in these patients as a result of effects on respiratory and motor function. Patients should also be made aware of the possibility of earlier operative vaginal delivery if fatigue of the trunk flexors is limiting. Despite the paucity of data addressing pregnancy outcomes in multiminicore disease, it is not possible to draw firm conclusions based on a single case study. A case report by Osada et al5 described a pregnant patient with suspected autosomal-dominant multiminicore disease. However, this case lacked definitive genetic diagnosis and management recommendations primarily focused on anesthetic concerns. Examining other congenital myopathies, both Awater and RudnikSchoneborn et al6,7 demonstrated minimal increased risk for adverse outcomes or operative deliveries compared with the general population. However, Rudnik-Schoneborn et al7 did infer that women with neuromuscular disease who were severely underweight as a result of limited muscle mass were at higher risk for preterm delivery. Rudnik-Schoneborn et al7 also found that patients with earlier onset of their congenital myopathy tended to observe a worsening of symptoms after delivery. Given the lack of data specific to multiminicore disease, it would be prudent to include counseling regarding the possibility of disease progression and irreversible postpartum handicap. REFERENCES 1. Jungbluth H. Multi-minicore disease. Orphanet J Rare Dis 2007; 2:31. 2. Romero NB, Monnier N, Viollet L, Cortey A, Chevallay M, Leroy JP, et al. Dominant and recessive central core disease associated with RYR1 mutations and fetal akinesia. Brain 2003; 126:2341–9. 3. Messina A, Hartley L, Main M, Kinali M, Jungbluth H, Muntoni F, et al. Pilot trial of salbutamol in central core and multi-minicore diseases. Neuropediatrics 2004;35: 262–6. 4. Saito O, Yamamoto T, Mizuno Y. Epidural anesthetic management using ropivacaine in a parturient with multi-minicore disease and susceptibility to malignant hyperthermia. J Anesth 2007;21:113. 5. Osada H, Masuda K, Seki K, Sekiya S. Multi-minicore disease with susceptibility to malignant hyperthermia in pregnancy. Gynecol Obstet Invest 2004;58:32–5. 6. Awater C, Zerres K, Rudnik-Schoneborn S. Pregnancy course and outcome in women with hereditary neuromuscular disorders: comparison of obstetric risks in 178 patients. Eur J Obstet Gynecol Reprod Biol 2012;162:153–9. 7. Rudnik-Schoneborn S, Glauner B, Rohrig D, Zerres K. Obstetric aspects in women with facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, and congenital myopathies. Arch Neurol 1997;54:888–94.
Multiminicore Disease in Pregnancy
OBSTETRICS & GYNECOLOGY
