Case of the Month
Pamela Heaberlin, MS, RN, NNP-BC ❍ Section Editor
Nonlethal Multiple Pterygium Syndrome Escobar Syndrome Robin L. Bissinger, PhD, APRN, NNP-BC, FAAN; Frances R. Koch, MD
ABSTRACT Nonlethal Escobar is a rare disorder that is a variant of multiple pterygium syndromes. It is a form of arthrogryposis multiplex congenita characterized by excessive webbing (pterygia), congenital contractures (arthrogryposis), and scoliosis. It is usually diagnosed in utero on fetal ultrasound and then confirmed in the neonatal period. A case of nonlethal neonatal Escobar is reported in a 35-week-and-6-day old infant who presented in utero with decreased fetal movement, oligohydramnios, and arthrogryposis. The etiologies from maternal causes were excluded prior to birth. Subsequent workup after birth led to a highly suspected diagnosis of nonlethal Escobar by the geneticist. The diagnosis was confirmed by a positive CHRNG gene sequence analysis after discharge. The infant demonstrated contractures and bilateral hip subluxation but was feeding well and was discharged home with outpatient follow-up. Treatment after discharge has been extensive secondary to difficulties associated with this disease.The clinical presentation of nonlethal Escobar, as well as diagnosis and treatment strategies, is provided with caregiving strategies. Key Words: arthrogryposis, contractures, Escobar, fetus, multiple pterygium syndrome, neonate, nonlethal Escobar
E
scobar syndrome is the nonlethal type of the rare congenital multiple-anomaly disorder, multiple pterygium syndrome (MPS). It is a rare inherited disorder that was first described in 1902 on the basis of observed malformations but was not identified as a distinct syndrome until 1978.1 This disorder affects both the fetus and newborn and is characterized by the following cardinal features: pterygia (webbing) of the neck, antecubital and popliteal areas; syndactyly and camptodactyly of the fingers; flexion contractures of multiple joints; distinct facial abnormalities (ptosis, antimongoloid eye slant, a prominent nasal bridge, micrognathia); Author Affiliations: College of Nursing (Dr Bissinger) and Division of Neonatology, Department of Pediatrics (Dr Koch), Medical University of South Carolina, Charleston. The authors declare no conflict of interest. Correspondence: Frances R. Koch, MD, Division of Neonatology, Medical University of South Carolina, 165 Ashley Ave, MSC 917, Charleston, SC 29425 (kochf@ musc.edu). Copyright © 2014 by The National Association of Neonatal Nurses DOI: 10.1097/ANC.0000000000000039 24
foot deformities (rocker-bottom feet), kyphoscoliosis, vertebral anomalies, and short stature.2 (See Table 1 for further definitions.) The pattern of malformations after birth directs the diagnosis. Although phenotypically and genetically heterogeneous, a prenatally lethal type of MPS also exists. Usually infants with nonlethal Escobar are first diagnosed in utero with arthrogryposis multiplex congenita (AMC), which is characterized by multiple severe joint contractures and decreased motility found throughout the body at birth. It is a group of disorders that involve the muscular, neurologic, and connective tissue. The incidence of AMC is 1 in 3000 births and is diagnosed on the basis of decreased fetal movement, joint contractures, and skeletal deformities seen prenatally.3 The major cause of AMC is decreased fetal movement (akinesia) in utero caused by either fetal or maternal disorders. Normal development of the joints cannot occur without fetal movement. Extra connective tissue will develop around the joints, further limiting movement and worsening the contractures.4 With the limited movement, the limbs and the ligaments themselves do not grow to normal length and can make outcomes after birth more difficult. Many genetic and nongenetic disorders can lead to arthrogryposis (Table 2). Arthrogryposis (bilateral curved or Advances in Neonatal Care • Vol. 14, No. 1 • pp. 24-29
Copyright © 2014 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
ANC-D-13-00032R1.indd 24
18/01/14 9:46 AM
Nonlethal Escobar Syndrome
TABLE 1. Terms and Definitions Pterygium
Wing-like structure, webbing, or triangular membrane forming across a body joint
Ptosis
Droopy eyelids
Kyphoscoliosis
Abnormal curvature of the spine in 2 directions
Syndactyly
Webbing of hands and/or feet
Camptodactyly
Permanent flexion of 1 or more fingers
Akinesia
Decreased fetal movement
Arthrogryposis
Bilateral hooked or curved joints
Arthrogryposis multiple congenita
Fixed joints in many areas of the body at birth
hooked joints) in the fetus can encompass several disease entities, and the formulation of a differential diagnoses presents a challenge to the clinician. Decreased fetal movement often leads to oligohydramnios and subsequent pulmonary hypoplasia, micrognathia, ocular hypertelorism, and short umbilical cord. The earlier it appears in gestation, the worse the disease and outcome. Arthrogryposis is now used as a descriptive term because it is often the actual physical finding that leads to other clinical signs seen in other syndromes or conditions. The term arthrogryposis is used to describe multiple types of congenital contractures caused by more than 150 specific disorders.5 Understanding the differential and making an accurate diagnosis are critical for treatment and improved outcomes. The differential diagnosis of Escobar syndrome is made by first separating the findings in the infant into 3 categories: (1) primarily limb involvement; (2) limb involvement as well as another body area; and (3) limb involvement with central nervous system disorder.5 Multiple pterygium syndrome is an example of limb involvement with other body areas and is an autosomal recessive condition. It is extremely rare with only a few reported case studies. The following case describes a 35–week-and-6day-old infant who presented at birth with webbing of the skin at her neck, knees, and elbows as well as multiple contractures. There are numerous types of pterygium syndromes with different features and forms of heritance. Baby M was subsequently diagnosed with neonatal nonlethal Escobar.
CASE REPORT Baby girl M was delivered by cesarean section for breech presentation and oligohydramnios at 35 weeks and 6 days old to a Caucasian 25-year-old
25
TABLE 2. Factors Contributing to Arthrogryposis Multiplex Congenitala A. Fetal (genetic, neurogenic, muscle, or connective tissue abnormalities; mechanical limitations to movement) • Genetics ○
X-linked (Xp11.3-q11.2; Xq23-27)
○
Autosomal recessive (chromosome 5 qter between D5S394 and D5S2069; distal arthrogryposis 9p 12.3, 11p15.5, 17q13.1)
Trisomies 13, 18, 21; Turner syndrome and triploidy Space: Insufficient room in the uterus for normal movement (twins, oligohydramnios, ovarian cyst, fibroids or abnormally shaped uterus) Muscle: Muscular atrophy, connective tissue abnormality, muscular dystrophy, mitochondrial disturbances Neuropathic: Central nervous system malformations (migrational brain disorder; CNS calcifications); structural anomalies Connective tissue: Diastrophic dysplasia (dwarfing); abnormal tendon attachment Other ○
•
•
•
• •
○
Ectodermal dysplasia (Cote Adamopoulos, Pantelakis syndrome, Trichooculodermovertebral [Alves] syndrome)
○
Kuskokwim disease
○
Van Bervliet syndrome
○
Arthrogryposis multiplex congenita distal
○
Gordon syndrome (distal IIA)
○
Freeman-Sheldon syndorme (whistling face syndrome)
○ Oculogelic amyoplasia • Illum syndrome (whistling face) • Oculmelic amyoplasia B. Maternal (infection, drugs, trauma, or maternal illness) • Maternal exposure to medications • Maternal hyperthermia in the first semester (fever or prolonged hot tubs use) • Maternal disease (diabetes mellitus, multiple sclerosis, myotonic dystrophy) • Viral infections (rubella, varicella, equine encephalitis) • Maternal autoantibodies to fetal antigens (myasthenia gravis) • Vascular compromise: lack of circulating blood leading to loss of neurons Abbreviation: CNS, central nervous system. a Data from Staheli et al.5
Advances in Neonatal Care • Vol. 14, No. 1 Copyright © 2014 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
ANC-D-13-00032R1.indd 25
18/01/14 9:46 AM
26
Bissinger and Koch
gravida 1, para 1, abortions 0. Prenatal labs were type A, Rh-positive blood along with hepatitis B surface antigen, group B streptococcus, HIV, Gonorrhea, Chlamydia, and quadruple screen all negative. The mother was rubella nonimmune. Her medical history was uncomplicated except for a history of depression 4 years before this pregnancy. The social history was negative for alcohol or drug abuse but included tobacco use that was stopped early in pregnancy. Family history was negative for birth defects or genetic disorders. This pregnancy was complicated by an abnormal routine anatomy scan at 21 weeks that revealed a nuchal fold of 8 mm, rocker bottom feet versus clubbed, anomalies of both hands held in a clenched position with a prominent fifth digit of the left and right hand as well as renal pyelectasis of the left kidney. The fetus appeared to be well grown. The mother was then referred to the Medical University of South Carolina Prenatal Wellness Center for genetic consultation. An amniocentesis revealed a normal alpha-fetoprotein of 0.75 MoM, a fetal karyotype of 46XX (normal female), and a negative FISH for Trisomy 13, 18, and 21. Repeat fetal ultrasounds showed a continued thickened nuchal fold as well as arthrogryposis of upper and lower extremities with possible sparing of the shoulder and hip joints by 27 weeks’ gestation. The parents were counseled during the entire pregnancy as to possible prognosis and etiology of the arthrogryposis that was to be determined after delivery. The prenatal workup for the arthrogryposis included a prenatal history that did not reveal any prior affected infants in other family members. There was no history of teratogen exposure, uterine anomalies, or maternal fever early in the pregnancy. The prenatal workup ruled out maternal diabetes, myasthenia gravis, and myotonic dystrophy. The mother had no reported viral illness during the pregnancy and workup for rubella, and coxsackie and enterovirus were negative. Final ultrasound prior to delivery showed oligohydramnios; therefore, 2 doses of betamethasone were given and the infant was delivered by scheduled cesarean section 2 days later. Arthrogryposis multiplex congenita can include complications such as lung hypoplasia, and other respiratory problems and jaw variations; therefore, a full stabilization team was available for the delivery. Pediatric ear, nose, and throat (ENT) were on standby to scope and obtain an airway if needed. At delivery, the infant presented with cyanosis, no respiratory effort, and a heart rate less than 60 beats per minute that did not respond to bag-valve-mask ventilation. Chest compressions were initiated for 1 minute and once intubated by ENT the heart rate was maintained above 100 beats per minute. Intubation was difficult secondary to micrognathia. The infant’s birth weight was 2200 g (
Pamela Heaberlin, MS, RN, NNP-BC ❍ Section Editor
Nonlethal Multiple Pterygium Syndrome Escobar Syndrome Robin L. Bissinger, PhD, APRN, NNP-BC, FAAN; Frances R. Koch, MD
ABSTRACT Nonlethal Escobar is a rare disorder that is a variant of multiple pterygium syndromes. It is a form of arthrogryposis multiplex congenita characterized by excessive webbing (pterygia), congenital contractures (arthrogryposis), and scoliosis. It is usually diagnosed in utero on fetal ultrasound and then confirmed in the neonatal period. A case of nonlethal neonatal Escobar is reported in a 35-week-and-6-day old infant who presented in utero with decreased fetal movement, oligohydramnios, and arthrogryposis. The etiologies from maternal causes were excluded prior to birth. Subsequent workup after birth led to a highly suspected diagnosis of nonlethal Escobar by the geneticist. The diagnosis was confirmed by a positive CHRNG gene sequence analysis after discharge. The infant demonstrated contractures and bilateral hip subluxation but was feeding well and was discharged home with outpatient follow-up. Treatment after discharge has been extensive secondary to difficulties associated with this disease.The clinical presentation of nonlethal Escobar, as well as diagnosis and treatment strategies, is provided with caregiving strategies. Key Words: arthrogryposis, contractures, Escobar, fetus, multiple pterygium syndrome, neonate, nonlethal Escobar
E
scobar syndrome is the nonlethal type of the rare congenital multiple-anomaly disorder, multiple pterygium syndrome (MPS). It is a rare inherited disorder that was first described in 1902 on the basis of observed malformations but was not identified as a distinct syndrome until 1978.1 This disorder affects both the fetus and newborn and is characterized by the following cardinal features: pterygia (webbing) of the neck, antecubital and popliteal areas; syndactyly and camptodactyly of the fingers; flexion contractures of multiple joints; distinct facial abnormalities (ptosis, antimongoloid eye slant, a prominent nasal bridge, micrognathia); Author Affiliations: College of Nursing (Dr Bissinger) and Division of Neonatology, Department of Pediatrics (Dr Koch), Medical University of South Carolina, Charleston. The authors declare no conflict of interest. Correspondence: Frances R. Koch, MD, Division of Neonatology, Medical University of South Carolina, 165 Ashley Ave, MSC 917, Charleston, SC 29425 (kochf@ musc.edu). Copyright © 2014 by The National Association of Neonatal Nurses DOI: 10.1097/ANC.0000000000000039 24
foot deformities (rocker-bottom feet), kyphoscoliosis, vertebral anomalies, and short stature.2 (See Table 1 for further definitions.) The pattern of malformations after birth directs the diagnosis. Although phenotypically and genetically heterogeneous, a prenatally lethal type of MPS also exists. Usually infants with nonlethal Escobar are first diagnosed in utero with arthrogryposis multiplex congenita (AMC), which is characterized by multiple severe joint contractures and decreased motility found throughout the body at birth. It is a group of disorders that involve the muscular, neurologic, and connective tissue. The incidence of AMC is 1 in 3000 births and is diagnosed on the basis of decreased fetal movement, joint contractures, and skeletal deformities seen prenatally.3 The major cause of AMC is decreased fetal movement (akinesia) in utero caused by either fetal or maternal disorders. Normal development of the joints cannot occur without fetal movement. Extra connective tissue will develop around the joints, further limiting movement and worsening the contractures.4 With the limited movement, the limbs and the ligaments themselves do not grow to normal length and can make outcomes after birth more difficult. Many genetic and nongenetic disorders can lead to arthrogryposis (Table 2). Arthrogryposis (bilateral curved or Advances in Neonatal Care • Vol. 14, No. 1 • pp. 24-29
Copyright © 2014 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
ANC-D-13-00032R1.indd 24
18/01/14 9:46 AM
Nonlethal Escobar Syndrome
TABLE 1. Terms and Definitions Pterygium
Wing-like structure, webbing, or triangular membrane forming across a body joint
Ptosis
Droopy eyelids
Kyphoscoliosis
Abnormal curvature of the spine in 2 directions
Syndactyly
Webbing of hands and/or feet
Camptodactyly
Permanent flexion of 1 or more fingers
Akinesia
Decreased fetal movement
Arthrogryposis
Bilateral hooked or curved joints
Arthrogryposis multiple congenita
Fixed joints in many areas of the body at birth
hooked joints) in the fetus can encompass several disease entities, and the formulation of a differential diagnoses presents a challenge to the clinician. Decreased fetal movement often leads to oligohydramnios and subsequent pulmonary hypoplasia, micrognathia, ocular hypertelorism, and short umbilical cord. The earlier it appears in gestation, the worse the disease and outcome. Arthrogryposis is now used as a descriptive term because it is often the actual physical finding that leads to other clinical signs seen in other syndromes or conditions. The term arthrogryposis is used to describe multiple types of congenital contractures caused by more than 150 specific disorders.5 Understanding the differential and making an accurate diagnosis are critical for treatment and improved outcomes. The differential diagnosis of Escobar syndrome is made by first separating the findings in the infant into 3 categories: (1) primarily limb involvement; (2) limb involvement as well as another body area; and (3) limb involvement with central nervous system disorder.5 Multiple pterygium syndrome is an example of limb involvement with other body areas and is an autosomal recessive condition. It is extremely rare with only a few reported case studies. The following case describes a 35–week-and-6day-old infant who presented at birth with webbing of the skin at her neck, knees, and elbows as well as multiple contractures. There are numerous types of pterygium syndromes with different features and forms of heritance. Baby M was subsequently diagnosed with neonatal nonlethal Escobar.
CASE REPORT Baby girl M was delivered by cesarean section for breech presentation and oligohydramnios at 35 weeks and 6 days old to a Caucasian 25-year-old
25
TABLE 2. Factors Contributing to Arthrogryposis Multiplex Congenitala A. Fetal (genetic, neurogenic, muscle, or connective tissue abnormalities; mechanical limitations to movement) • Genetics ○
X-linked (Xp11.3-q11.2; Xq23-27)
○
Autosomal recessive (chromosome 5 qter between D5S394 and D5S2069; distal arthrogryposis 9p 12.3, 11p15.5, 17q13.1)
Trisomies 13, 18, 21; Turner syndrome and triploidy Space: Insufficient room in the uterus for normal movement (twins, oligohydramnios, ovarian cyst, fibroids or abnormally shaped uterus) Muscle: Muscular atrophy, connective tissue abnormality, muscular dystrophy, mitochondrial disturbances Neuropathic: Central nervous system malformations (migrational brain disorder; CNS calcifications); structural anomalies Connective tissue: Diastrophic dysplasia (dwarfing); abnormal tendon attachment Other ○
•
•
•
• •
○
Ectodermal dysplasia (Cote Adamopoulos, Pantelakis syndrome, Trichooculodermovertebral [Alves] syndrome)
○
Kuskokwim disease
○
Van Bervliet syndrome
○
Arthrogryposis multiplex congenita distal
○
Gordon syndrome (distal IIA)
○
Freeman-Sheldon syndorme (whistling face syndrome)
○ Oculogelic amyoplasia • Illum syndrome (whistling face) • Oculmelic amyoplasia B. Maternal (infection, drugs, trauma, or maternal illness) • Maternal exposure to medications • Maternal hyperthermia in the first semester (fever or prolonged hot tubs use) • Maternal disease (diabetes mellitus, multiple sclerosis, myotonic dystrophy) • Viral infections (rubella, varicella, equine encephalitis) • Maternal autoantibodies to fetal antigens (myasthenia gravis) • Vascular compromise: lack of circulating blood leading to loss of neurons Abbreviation: CNS, central nervous system. a Data from Staheli et al.5
Advances in Neonatal Care • Vol. 14, No. 1 Copyright © 2014 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
ANC-D-13-00032R1.indd 25
18/01/14 9:46 AM
26
Bissinger and Koch
gravida 1, para 1, abortions 0. Prenatal labs were type A, Rh-positive blood along with hepatitis B surface antigen, group B streptococcus, HIV, Gonorrhea, Chlamydia, and quadruple screen all negative. The mother was rubella nonimmune. Her medical history was uncomplicated except for a history of depression 4 years before this pregnancy. The social history was negative for alcohol or drug abuse but included tobacco use that was stopped early in pregnancy. Family history was negative for birth defects or genetic disorders. This pregnancy was complicated by an abnormal routine anatomy scan at 21 weeks that revealed a nuchal fold of 8 mm, rocker bottom feet versus clubbed, anomalies of both hands held in a clenched position with a prominent fifth digit of the left and right hand as well as renal pyelectasis of the left kidney. The fetus appeared to be well grown. The mother was then referred to the Medical University of South Carolina Prenatal Wellness Center for genetic consultation. An amniocentesis revealed a normal alpha-fetoprotein of 0.75 MoM, a fetal karyotype of 46XX (normal female), and a negative FISH for Trisomy 13, 18, and 21. Repeat fetal ultrasounds showed a continued thickened nuchal fold as well as arthrogryposis of upper and lower extremities with possible sparing of the shoulder and hip joints by 27 weeks’ gestation. The parents were counseled during the entire pregnancy as to possible prognosis and etiology of the arthrogryposis that was to be determined after delivery. The prenatal workup for the arthrogryposis included a prenatal history that did not reveal any prior affected infants in other family members. There was no history of teratogen exposure, uterine anomalies, or maternal fever early in the pregnancy. The prenatal workup ruled out maternal diabetes, myasthenia gravis, and myotonic dystrophy. The mother had no reported viral illness during the pregnancy and workup for rubella, and coxsackie and enterovirus were negative. Final ultrasound prior to delivery showed oligohydramnios; therefore, 2 doses of betamethasone were given and the infant was delivered by scheduled cesarean section 2 days later. Arthrogryposis multiplex congenita can include complications such as lung hypoplasia, and other respiratory problems and jaw variations; therefore, a full stabilization team was available for the delivery. Pediatric ear, nose, and throat (ENT) were on standby to scope and obtain an airway if needed. At delivery, the infant presented with cyanosis, no respiratory effort, and a heart rate less than 60 beats per minute that did not respond to bag-valve-mask ventilation. Chest compressions were initiated for 1 minute and once intubated by ENT the heart rate was maintained above 100 beats per minute. Intubation was difficult secondary to micrognathia. The infant’s birth weight was 2200 g (
