Case Report 45
Early Postnatal Diagnosis of Costello Syndrome Costello Syndrom – frühe postnatale Diagnose
Authors
S. Kargl1, M. Meissl2, W. Pumberger1
Affiliations
1
2
Key words ▶ genetic disorder ● ▶ fetal tachycardia ● ▶ feeding difficulties ● ▶ cutaneous lesions ● ▶ cardiac defects ● ▶ cancer susceptibility ●
Abstract
Zusammenfassung
Costello syndrome is a rare congenital disease with typical craniofacial and musculoskeletal features, cutaneous lesions, cardiac defects and cancer susceptibility. Affected patients show severe feeding difficulties for the first years of life and developmental delay. We present the case of a patient, in whom fetal tachycardia, polyhdramnios and physical characteristics led to an early diagnosis of Costello syndrome. Based on this patient we describe challenges and problems of therapeutic management of infants with Costello syndrome.
Beim Costello Syndrom handelt es sich um eine äußerst seltene kongenitale Erkrankung. Auf grund eines genetischen Defekts auf Chromosom 11 kommt es neben Hautveränderungen, Herzerkrankungen und einem erhöhten Tumorrisiko zu typischen kraniofazialen und muskuloskeletalen Stigmata. Wir präsentieren den Fall eines Kindes, bei dem eine fetale Tachykardie, ein Polyhydramnion und typische äußere Merkmale zur frühen Diagnose eines Costello Syndroms führten. Anhand dieses Patienten skizzieren wir die Herausforderungen und Probleme bei der Behandlung von Kindern mit Costello Syndrome.
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Introduction
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Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1377028 Published online: July 25, 2014 Klin Padiatr 2015; 227: 45–47 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0300-8630 Correspondence Dr. Simon Kargl Department of Pediatric Surgery Women’s and Children’s Hospital Linz Krankenhausstrasse 26–30 4020 Linz Austria Tel.: + 43/505/546323 305 Fax: + 43/505/546323 354 [email protected]
RASopathy syndromes are congenital diseases caused by germline mutations in the RAS signaling pathway genes. The RAS (rat sarcoma) protoongogen plays an important role in cellular growth and differentiation. This RASopathy syndromes including Costello syndrome, Noonan syndrome, Legius syndrome, LEOPARD syndrome, neurofibromatosis 1 and the cardio-facio-cutane syndrome present with similar clinical signs such as cutaneous lesions, cardiac defects and cancer susceptibility. Early postnatal diagnosis can be challenging because of absent or uncharacteristic craniofacial features. The complete clinical picture may only evolve in the course of time. We report the case of a neonate in whom diagnostic work-up of polyhydramnios and fetal tachyarrythmia led to a diagnosis of Costello syndrome.
Case report
▼
In a pregnant 41-year-old woman (gravida 2, para 1) routine ultrasound examination at 20 weeks of gestation revealed polyhydramnios. Additionally, sub-
▼
sequent thorough ultrasound screening showed an intracardiac echogenic focus and cerebral plexus cysts. Because of these abnormalities and the maternal age amniocentesis was performed at 21 weeks of gestation: fluorescent in situ hybridization (FISH) was normal and no chromosomal anomalies were found. The further course of the pregnancy was monitored via regular ultrasound examinations, but did not reveal any additional abnormal findings. At 39 weeks of gestation routine cardiotocogram (CTG) suddenly revealed severe fetal tachyarrythmia leading to immediate cesarean section. The newborn girl was breathing spontaneously and had an APGAR score of 8/9/9. Initial oxygen requirements could be reduced and electrocardiogram (ECG) showed atrial flutter with 3:1 ▶ Fig. 1). Medical treatment with conduction ( ● Sotalol (Sotacor) and Propafenon (Rytmonorma) plus 2 cardioversions failed to achieve cardiac stabilization. Triple therapy with Sotalol, Propafenon and Metildigoxin (Lanitop) finally resulted in sinus rhythm. Repeated echocardiography did not reveal any structural heart defect, cerebral ultrasound examination was normal, too. In the first weeks of life the child developed a bulky forehead, full lips and a wide nasal bridge.
Kargl S et al. Early Postnatal Diagnosis of … Klin Padiatr 2015; 227: 45–47
Downloaded by: University of Queensland. Copyrighted material.
Schlüsselwörter ▶ genetische Erkrankung ● ▶ fetale Tachykardie ● ▶ Ernährungsschwierigkeiten ● ▶ Hautveränderungen ● ▶ Herzerkrankungen ● ▶ erhöhtes Tumorrisiko ●
Department of Pediatric Surgery, Women’s and Children’s Hospital Linz, Linz, Austria Department of Pediatrics, Women’s and Children’s Hospital Linz, Linz, Austria
Fig. 1 ECG showing atrial flutter at the first day of life.
▶ Fig. 3). The voice of the child was described as deviation ( ● hoarse. Because of these characteristic features combined with polyhydramnios and fetal tachycardia Costello syndrome was suspected. Genetic testing revealed a heterozygote missense-mutation {c.34 G > A (p.G12S)} in the HRAS gene on chromosome 11. Since birth the child did not tolerate oral feedings and repeatedly presented with massive abdominal distention and bowel movements were small and doughy. Contrast enema was performed and was consistent with Hirschsprung disease but rectal suction biopsies were normal. After 6 weeks of nasogastric tube feeding percutane endoscopic gastrostomy (PEG) was performed under general anesthesia. After resolution of local wound healing disorder the gastrostomy seemed to work well but the child still did not gain weight. Contrast enema depicted gastrocolic fistula which was divided via open surgical approach. Enteral alimentation was now ensured and the child gained weight but showed persistent growth retardation (
Early Postnatal Diagnosis of Costello Syndrome Costello Syndrom – frühe postnatale Diagnose
Authors
S. Kargl1, M. Meissl2, W. Pumberger1
Affiliations
1
2
Key words ▶ genetic disorder ● ▶ fetal tachycardia ● ▶ feeding difficulties ● ▶ cutaneous lesions ● ▶ cardiac defects ● ▶ cancer susceptibility ●
Abstract
Zusammenfassung
Costello syndrome is a rare congenital disease with typical craniofacial and musculoskeletal features, cutaneous lesions, cardiac defects and cancer susceptibility. Affected patients show severe feeding difficulties for the first years of life and developmental delay. We present the case of a patient, in whom fetal tachycardia, polyhdramnios and physical characteristics led to an early diagnosis of Costello syndrome. Based on this patient we describe challenges and problems of therapeutic management of infants with Costello syndrome.
Beim Costello Syndrom handelt es sich um eine äußerst seltene kongenitale Erkrankung. Auf grund eines genetischen Defekts auf Chromosom 11 kommt es neben Hautveränderungen, Herzerkrankungen und einem erhöhten Tumorrisiko zu typischen kraniofazialen und muskuloskeletalen Stigmata. Wir präsentieren den Fall eines Kindes, bei dem eine fetale Tachykardie, ein Polyhydramnion und typische äußere Merkmale zur frühen Diagnose eines Costello Syndroms führten. Anhand dieses Patienten skizzieren wir die Herausforderungen und Probleme bei der Behandlung von Kindern mit Costello Syndrome.
▼
Introduction
▼
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1377028 Published online: July 25, 2014 Klin Padiatr 2015; 227: 45–47 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0300-8630 Correspondence Dr. Simon Kargl Department of Pediatric Surgery Women’s and Children’s Hospital Linz Krankenhausstrasse 26–30 4020 Linz Austria Tel.: + 43/505/546323 305 Fax: + 43/505/546323 354 [email protected]
RASopathy syndromes are congenital diseases caused by germline mutations in the RAS signaling pathway genes. The RAS (rat sarcoma) protoongogen plays an important role in cellular growth and differentiation. This RASopathy syndromes including Costello syndrome, Noonan syndrome, Legius syndrome, LEOPARD syndrome, neurofibromatosis 1 and the cardio-facio-cutane syndrome present with similar clinical signs such as cutaneous lesions, cardiac defects and cancer susceptibility. Early postnatal diagnosis can be challenging because of absent or uncharacteristic craniofacial features. The complete clinical picture may only evolve in the course of time. We report the case of a neonate in whom diagnostic work-up of polyhydramnios and fetal tachyarrythmia led to a diagnosis of Costello syndrome.
Case report
▼
In a pregnant 41-year-old woman (gravida 2, para 1) routine ultrasound examination at 20 weeks of gestation revealed polyhydramnios. Additionally, sub-
▼
sequent thorough ultrasound screening showed an intracardiac echogenic focus and cerebral plexus cysts. Because of these abnormalities and the maternal age amniocentesis was performed at 21 weeks of gestation: fluorescent in situ hybridization (FISH) was normal and no chromosomal anomalies were found. The further course of the pregnancy was monitored via regular ultrasound examinations, but did not reveal any additional abnormal findings. At 39 weeks of gestation routine cardiotocogram (CTG) suddenly revealed severe fetal tachyarrythmia leading to immediate cesarean section. The newborn girl was breathing spontaneously and had an APGAR score of 8/9/9. Initial oxygen requirements could be reduced and electrocardiogram (ECG) showed atrial flutter with 3:1 ▶ Fig. 1). Medical treatment with conduction ( ● Sotalol (Sotacor) and Propafenon (Rytmonorma) plus 2 cardioversions failed to achieve cardiac stabilization. Triple therapy with Sotalol, Propafenon and Metildigoxin (Lanitop) finally resulted in sinus rhythm. Repeated echocardiography did not reveal any structural heart defect, cerebral ultrasound examination was normal, too. In the first weeks of life the child developed a bulky forehead, full lips and a wide nasal bridge.
Kargl S et al. Early Postnatal Diagnosis of … Klin Padiatr 2015; 227: 45–47
Downloaded by: University of Queensland. Copyrighted material.
Schlüsselwörter ▶ genetische Erkrankung ● ▶ fetale Tachykardie ● ▶ Ernährungsschwierigkeiten ● ▶ Hautveränderungen ● ▶ Herzerkrankungen ● ▶ erhöhtes Tumorrisiko ●
Department of Pediatric Surgery, Women’s and Children’s Hospital Linz, Linz, Austria Department of Pediatrics, Women’s and Children’s Hospital Linz, Linz, Austria
Fig. 1 ECG showing atrial flutter at the first day of life.
▶ Fig. 3). The voice of the child was described as deviation ( ● hoarse. Because of these characteristic features combined with polyhydramnios and fetal tachycardia Costello syndrome was suspected. Genetic testing revealed a heterozygote missense-mutation {c.34 G > A (p.G12S)} in the HRAS gene on chromosome 11. Since birth the child did not tolerate oral feedings and repeatedly presented with massive abdominal distention and bowel movements were small and doughy. Contrast enema was performed and was consistent with Hirschsprung disease but rectal suction biopsies were normal. After 6 weeks of nasogastric tube feeding percutane endoscopic gastrostomy (PEG) was performed under general anesthesia. After resolution of local wound healing disorder the gastrostomy seemed to work well but the child still did not gain weight. Contrast enema depicted gastrocolic fistula which was divided via open surgical approach. Enteral alimentation was now ensured and the child gained weight but showed persistent growth retardation (
