Fraser Syndrome – a Dilemma to Parents

CASE REPORT tal care from a local rural hospital. In first pregnan- According to the revised Fraser syndrome criteria, no specific methods to prevent this condition, but Figure 1 & 2: show multiple gross malformations. cy, there was oligohydramnios delivered at 30 our findings in this case, and based on previous genetic testing may help to identify families at risk. Including anopthalmia, dysmorphic face and limb weeks of gestation, the hospital report indicates pregnancy outcomes our patient fulfills the criteria defects. (Parents of the newborn had given written FRASER SYNDROME – A DILEMMA TO limb defects and anophthalmia, child died immedi- of Fraser syndrome. Couple, who have diagnosis of Fraser syndrome at consent to take the pictures shown above) ately after birth. In second pregnancy, the parents first pregnancy, should have genetic counseling. PARENTS opted for a termination at 20 weeks due to inade- There is no difference in incidence of Fraser Mother with Fraser syndrome neonatal history REFERENCES quate amniotic fluid. In the recent pregnancy, they syndrome in female and male children. Some racial should be kept on critical prenatal ultrasound 2 Shazia Sultana¹ Rubina Hussain¹Natasha Lateef ¹ Aijaz Ali Leena Hani³ received regular antenatal care at local Hospital, predisposition has been observed, as it seems to be checking that may be helpful for diagnosis during 1. Narang M, Kumar M, Shah D. Fraser-crypthohthal- ¹ Department of Obstetrics and Gynecology, Ziauddin University but due to oligohydramnios, she was referred to a more common in gypsy families as well as in families early pregnancy. Further research should be mos syndrome with colonic atresia. Indian J pedi- 2Registrar in Department of Pediatrics, Ziauddin Hospital tertiary-care hospital. Here at Ziauddin Hospital with history of the same malformation 6. The exact 3 Fifth Year Medical Student, Ziauddin University conducted to help provide treatment to such atr.2008;75:189-91 ultrasound was requested which revealed; a single etiology is unknown, and it is believed that most of parents. 2. Adnan AS, Sorath NS. Fraser Syndrome – Case live fetus corresponding to gestational age of 32±2 the anomalies are due to defects in programmed Report. JCPSP.2015;25:S124-S126 weeks breech presentation with an amniotic fluid cell death and apoptosis as well as in metabolism of 3. Vogel MJ, Van Zon P, Brueton L, Gijzen M, Van Tuil ABSTRACT index (AFI) of 2.3 cm. Umbilical artery Doppler retinoid 7. The manifestation of autosomal recessive MC, Cox P, Schanze D, kariminejad A, Ghaderi –Sohi showed normal indices. Previous prenatal disorders occurs when the affected child receives S, Blair E et al. Mutations in GRIP1 cause Fraser In this case report the patient belongs to rural Sindh, with poor prenatal care. She came with her third preg- ultrasound could not be documented due to the abnormal genes for the same trait from both syndrome. J Med Genet. 2012 May;49(5):303-6. nancy to Ziauddin Hospital referred from interior of Sindh, with the history of previous two premature deliver- unavailability.. In view of her gynecological history a parents. If the individual receives one normal and 4. Slavotinek, A., Li, C., Sherr, E. H., Chudley, A. E. ies due to oligohydramnios. cesarean section was planned. The neonate was a one defective gene, the neonate will only be a Mutation analysis of the FRAS1 gene demonstrates limp male, who did not cry, had no spontaneous carrier and will not show any symptoms. Therefore, new mutations in a propositus with Fraser syndrome. Fraser syndrome is a rare congenital condition that includes multi-organ abnormalities and usually has a breathing and was bradycardic. He was aggres- the risk of a diseased child is 25% when both parents Am. J. Med Genet. 140A: 1909-1914, 2006. sively resuscitated and intubation was attempted, carry defective genes, 50% of their offspring will be poor prognosis. The most obvious deformities noted are cryptophthalmos, syndactyly, laryngeal stenosis, 5. Van Haelst MM, Scambler PJ. Fraser syndrome which was unsuccessful due to severe laryngeal carriers, and 25% will have normal genes. Hence, in collaboration group. Fraser syndrome: a clinical and bilateral renal agenesis, displacement of umbilicus, undescended testes and clitoromegaly. The trans- stenosis. Ventilator support was provided with the consanguineous marriages, there is more risk of the study of 59 cases and evaluation of diagnostic mission of the syndrome is autosomal recessive and is caused by a mutation in the FRAS1, FREM2 or GRIP1 assistance of a neonatal laryngeal mask. same defective genes and the subsequent transfer criteria. Am J Med Genet A2007;143:3194-203. genes. The pathology, however, is unclear, but the mutations are known to alter programmed cell death, to their children. 6. Fraser Syndrome- Review Article. DoveMed. com. causing defects in the metabolism of retinoid. Gross examination revealed a male baby weighing 8,2015(http://www.dovemed.com/fraser-syn- 1.5 kg. Craniofacial examination revealed left In our case, the patient has suffered from the same drome/) The details of the case are the patient was of a 20-year-old female presented in her 3rd pregnancy at 34 cryptophthalmos with an eye ball palpable disorder thrice. The literature reviews suggest that 7. Hambire SD, Bhavsar PP. Meenakshi B. Jayakar AV. weeks of gestational amenorrhea which was complicated with severe oligohydramnios. She delivered an beneath. His right eye had a narrow palpebral consanguinity is in 15–24% of cases and the recur- Freser-crypthalmos syndrome with cardiovascular 8 underweight baby via cesarean section who had a poor cry and bradycardia at the time of birth. His struc- fissure and normal eyeball but a deformed pinna. rence rate among siblings is 25% . malformations: A rare case. Indian Pediatr. Besides these findings, he had bilateral syndactyly, tural defects included bilateral syndactly, laryngeal stenosis and undescended testes. The patient also had 2003;888-90. laryngeal stenosis, multiple skeletal defects and Fraser syndrome can be diagnosed by ultrasound 8. Kalaniti K, Sandhya V. Fraser syndrome in three a history of two cesarean sections. Her first child was born with limb defects and anophthalmia and died undescended testes. Thus, the diagnosis of Fraser during pregnancy, which may show hyper echoic consecutive siblings. Oman J Ophthalmol. 2011; immediately after birth. Her second child was terminated due to severely reduced amniotic fluid. Patients syndrome was made. Conventional karyo typing lungs, oligohydramnios and microphthalmia. It can 4(2): 87-9. with a previous history should have genetic counseling beforehand and prenatal ultrasound based diagno- done of both parents, and did not show any chro- also be detected based on the previous pregnancy 9. Leung E, Diaz-Barbosa M, Alabiad C, Hodapp E, sis. mosomal abnormalities. losses owing to still birth, oligohydramnios, and renal Tse D, Murray TG, et al. Pre-natal ultrasonographic agenesis. In our case, the patient received subopti- detection of ophthalmic disease. J Pediatr Opthal- KEYWORDS: Fraser Syndrome, Cryptophthalmos, Syndactyly DISCUSSION mal antenatal care and had no ultrasound report mol strabismus 2012;49:26-9 showing any abnormality. Also, her previous history 10. C. Berg, a. Geipel, u. germer, a. pertersen-han- Corresponding Author Fraser syndrome was previously known as cryptoph- of fetal loss was not considered as a high risk for any sen*. m. koch-dorfler and u. gembruch. prenatal thalmos syndrome. Later, it was revised and noted genetic disorder. Each time she underwent a cesar- Dr. Shazia Sultana detection of freser sundrome without cryptophthal- that cryptophthalmos may not be a compulsory ean section and hysterectomy, it affected her mos: case report and review of the literature. INTRODUCTION Assistant Professor, Ziauddin University Hospital feature. It can be caused by a homozygous or potential chances of conceiving. When the patient ultrasound obstet gynecol 2001; 18:7 CASE REPORT Email: [email protected] compound heterozygous mutation in the FRAS1 was received, her ultrasound scans identified an AFI The most common organisms causing Infective gene (607830) on chromosome 4q21, the FREM2 of about 2 cm, because of which it was not possible endocarditisis Staphylococcus Aureus. Incidence A case of 24 year old gentleman, known intrave- gene (608945) on chromosome 13q13, or the GRIP1 to identify any anomaly. With the intention to save of IE in intravenous drug abusers is 2 to 4 cases per nous drug abuser, presented with the sudden onset gene (604597) on chromosome 12q14. Therefore, the fetus, a delivery was planned immediately; the 1000 years of intravenous drug abuse.It is more of bilateral visual loss for few hours. No associated INTRODUCTION recessive condition. At least five mutations were 3,4 Fraser syndrome is an optimal term. It is a rare auto- born child had multiple anomalies including common in males (3:1) Another review of 105 ocular symptoms of redness, lacrimation, peri-orbit- identified in the FRAS1 gene, which encodes a somal recessive disorder with variable expressivity 4. syndactyly, cryptophthalmos and laryngeal atresia. patients of infective endocarditis in intravenous al pain, headache, diplopia or proptosis were Fraser syndrome is a clinical condition that affects putative extracellular matrix protein 3. As an autoso- In 1986, Thomas et al established major and minor Even after resuscitation efforts, it was not possible to drug abuser at a tertiary care hospital in Vancouver, found. There was no history of visual impairment in multiple organs. The fetus or newborn has a very mal recessive disorder, this condition should only criteria to diagnose Fraser syndrome. It was modi- save the child. A subsequent diagnosis of Fraser revealed that 86% involve right side, while 14% had the past. He was having high grade, intermittent poor survival rate. The major malformation includes occur when defective genes are inherited from 5 fied by Van Haelstetal.5 in 2007 as; Major criteria syndrome was made. It is imperative that the left sided involvement. Septic embolization is a fever for 3 weeks. Fever was associated with joints an eye defect called cryptophthalmos, which is both parents. 1 were Syndactyly, Cryptophthalmos spectrum, mother receives adequate antenatal care, includ- common complication of IE. Visual complications pain and there was also significant pain at the tips present in 93% of cases. Syndactyly is present in 54% Urinary tract abnormalities, Ambiguous genitalia, ing an ultrasound scan in early pregnancy 9. Other due to micro-embolization and staphylococcal of his fingers. He denied any history of rash or oral of cases. Other defects include urinary anomalies, CASE REPORT Laryngeal and tracheal anomalies, Positive family symptoms like syndactyly, ear and facial abnormali- bacteremia are common in patients with infective ulcers. laryngeal stenosis or displacement, along with 2 history. The minor criteria were Anorectal defects, ties can also be found on an ultrasound. Therefore, endocarditis. We present a case of young, intrave- skeletal deformities 1. The main causes of death are Our patient was a 20-year-old female, married for Dysplastic ears, Skull ossification defects, Umbilical in the case of oligohydramnios, fluid instillation in nous drug abuser with vision loss. In our case, the On examination, his temperature was 100 degree laryngeal atresia and renal agenesis. four years to her first cousin. Both parents were abnormalities, Nasal anomalies. amniotic cavity can be considered to improve the likely cause of vision impairment is microemboliza- Fahrenheit, heart rate 110 beats/minute & regular, healthy with no family history of any known abnor- visualization of the kidney, face, ears, and limbs 10. tion of bacteria in the basilar artery, leading to Respiratory rate 18 breaths/minute, Blood pressure: The incidence is 0.043 per 10,000 live-born infants malities. She was in her third pregnancy, para 1+1, Diagnosis of Fraser syndrome is based on either 3 vasospasm of posterior circulation.Early reversibility 110/70 mm Hg. His general physical examination and 1.1 in 10,000 stillbirths, making it a rare syndrome referred from rural area with 34 weeks of gestational major criteria, 2 major and 2 minor criteria, or 1 In conclusion, Fraser syndrome is a lethal genetic is due to appropriate administration of antibiotics. revealed Osler’s nodes(tender lesions found on 2. About 15% of cases were born to consanguineous amenorrhea, along with severe oligohydramnios. In major and 3 minor criteria. disorder with a poor prognosis. Currently, there are partners, which is a sign that this is an Autosomal her previous pregnancies also, she sought antena-

42 PAKISTAN JOURNAL OF MEDICINE AND DENTISTRY 2017, VOL. 6 (03)

finger pulps). Ophthalmological examination infective endocarditis, embolic events occur in as 3 .Tung MK, Light M, Giri R, Lane S, Appelbe A, showed visual acuity of light perception only. Pupils many as 50% of all patients.Embolic stroke can result Harvey C, Athan E. Evolving epidemiology of inject- were 3 mm in size, bilaterally equal and reactive to from embolization of an artery in the central circula- ing drug use‐associated infective endocarditis: A light.There were few pale-centered hemorrhagic tion from a variety of sources. In infective endocar- regional centre experience. Drug and alcohol areas seen on the retina (Roth spots). (Figure 1) ditis, besides clot, fibrin, and pieces of atheroma- review. 2015 ;34(4):412-7. Fundi and maculae were normal. Neurological tous plaque, emboli include bacterial clumps. 4.Slipczuk L, Codolosa JN, Davila CD, Romero-Corral assessment was unremarkable. On auscultation of Superficial branches of cerebral and cerebellar A, Yun J, Pressman GS, Figueredo VM. Infective heart, there was early systolic murmur of grade 2/6 arteries are the most frequent targets of emboli. endocarditis epidemiology over five decades: a on tricuspid area. Most emboli lodge in the middle cerebral artery systematic review. PloS one. 2013 ;8(12):e82665. distribution because 80% of the blood carried by 5. Moss R, Munt B. Injection drug use and right sided His lab workup showed hemoglobin of 12.8 mg/dl, the large neck arteries flow through the middle endocarditis. Heart. 2003 ;89(5):577-81. Total leukocyte count of 26,000 /cu mm(4-11), Plate- cerebral arteries, this is contrary to our case. 6.Dickerman SA, Abrutyn E, Barsic B, Bouza E, lets were 150,000/ cu mm(150-400,000), Urea: Cecchi E, Moreno A, Doco-Lecompte T, Eisen DP, 53mmol/L(<40), Creatinine: 1.59 mg/dl, SGPT: The neurological outcome from strokecaused by Fortes CQ, Fowler VG, Lerakis S. The relationship 115units/liter (up to40 units/liter),Gamma GT:226 septic embolization depends not only on the between the initiation of antimicrobial therapy and units/liter (11-50), Alkaline phosphatase:167 IU/liter occluded vascular territory but also on the ability of the incidence of stroke in infective endocarditis: an (39-117), ESR:79 mm/hour (1-12), CRP:183 mg/liter the embolus to cause vasospasm by acting as a analysis from the ICE Prospective Cohort Study (5), Urine detailed report revealed Red cells:10 vascular irritant. Septic emboli in infective endocar- (ICE-PCS). American heart journal. 2007 a. Left parieto-occipital area of diffusion restriction mg/dl, no casts.Ultrasound abdomen was normal. ditis are very irritant to the vessel and at times can ;154(6):1086-94. Chest x ray showed multiple heterogenous opaci- cause necrotic arteritis. The vasospasm can occur ties propagating alikely possibility of septic emboli. in the vascular segment where the embolus lodges MRI brain showed focal areas of hyperintensities or can involve the entire arterial tree. Vasospasm seen in the left occipital lobe and right centrum tends to occur in younger patients, probably semiovale location on diffusion weighted sequenc- because the vessels are more pliable and less es, few hyperintense foci appreciated on flair atherosclerotic.Degree of damage by embolic images seen in the right parieto-occipital lobe. occlusion depends on the time emboli remained in Likely possibility is of multiple ischemic areas due to cerebral circulation and richness of collateral circu- cardio-embolization (figure 2). Echocardiography lation. Although MRI brain was done after 24 hours showed intracardiac vegetation seen attached to in our case, it showed multiple areas of diffusion anterior mitral leaflet (10mm), mild Mitral regurgita- restriction in parieto-occipital areas and centrum tion and Tricuspid regurgitation was also noted. semiovale, with the impression of cerebral septic Three sets of blood cultures were sent and treat- emboli. In our case, likely possibility of vision impairment started empirically for native valve endocardi- ment is micro embolization of bacteria to basilar tis. His blood culture showed growth of Staphylo- artery leading to vasospasm of posterior circulation. coccus Aureus.HIV serology’s, hepatitis profile and As mentioned earlier, in our case there was a delay fungal cultures were negative. Patient was man- in neuro imaging so MRA brain failed to show any aged on broad spectrum antibiotics by the team of vascular stenosis or occlusion. Our case clearly Figure 1: EYE FUNDUS SHOWING ROTH SPOTS b) Right centrum semiovale area of diffusion restric- general physician, cardiologist, Infectious disease delineates the thought of cerebral embolic tion expert, pulmonologist and neurologist. Cardiotho- phenomenon and its reversibility due to appropri- racic surgery input was taken and they advise ate and timely administration of antibiotics leading Figure 2(a&b): MRI BRIAN (DWI SEQUENCES) conservative management. His vision improved to reversal of vasospasm as proven in international after 18 hours of hospital stay, although his fever collaboration on endocarditis. A prospective remained for another week. Antibiotics were cohort study showed that the crude incidence of continued for total of 4 weeks. Follow up echocardi- stroke in patients receiving appropriate antimicrobi- ography revealed reduction in size of vegetation al therapy was 4.82/1,000 patient days in the first from 10 mm to 6 mm. week of therapy and decreased to 1.71/1,000 patient days in the second week. This rate contin- DISCUSSION ued to decline with additional therapy6.So our case emphasizes the importance of early identification Sudden simultaneous, bilateral visual loss is rare and and management of infective endocarditis has a restricted differential diagnosis which includes patients with septic embolization to brain. bilateral occipital lobe infarction or hemorrhage, pituitary apoplexy, bilateral sequential ischemic REFERENCES optic neuropathy, bilateral acute glaucoma, bilateral optic neuritis, bilateral retinal detachments, 1. Klig JE. Ophthalmologic complications of system- bilateral central retinal artery and vein occlusions. In ic disease. Emergency medicine clinics of North our case, examination findings of normal bilaterally America. 2008 ;26(1):217-31. equal and reactive pupils, normal optic discs, with 2. Jung J, Lee J, Yu SN, Kim YK, Lee JY, Sung H, Kim the normal angiography of retinal vessels, exclude MN, Kim SH, Lee SO, Choi SH, Woo JH. Incidence all other possibilities of bilateral visual loss and local- and risk factors of ocular infection caused by Staph- ized the lesion at visual cortex. ylococcus aureus bacteremia. Antimicrobial agents Septic embolization is a common complication of and chemotherapy. 2016 ;60(4):2012-7. SHAZIA SULTANA, RUBINA HUSSAIN, NATASHA LATEEF, AIJAZ ALI, LEENA HANI

tal care from a local rural hospital. In first pregnan- According to the revised Fraser syndrome criteria, no specific methods to prevent this condition, but Figure 1 & 2: show multiple gross malformations. cy, there was oligohydramnios delivered at 30 our findings in this case, and based on previous genetic testing may help to identify families at risk. Including anopthalmia, dysmorphic face and limb weeks of gestation, the hospital report indicates pregnancy outcomes our patient fulfills the criteria defects. (Parents of the newborn had given written limb defects and anophthalmia, child died immedi- of Fraser syndrome. Couple, who have diagnosis of Fraser syndrome at consent to take the pictures shown above) ately after birth. In second pregnancy, the parents first pregnancy, should have genetic counseling. opted for a termination at 20 weeks due to inade- There is no difference in incidence of Fraser Mother with Fraser syndrome neonatal history REFERENCES quate amniotic fluid. In the recent pregnancy, they syndrome in female and male children. Some racial should be kept on critical prenatal ultrasound received regular antenatal care at local Hospital, predisposition has been observed, as it seems to be checking that may be helpful for diagnosis during 1. Narang M, Kumar M, Shah D. Fraser-crypthohthal- but due to oligohydramnios, she was referred to a more common in gypsy families as well as in families early pregnancy. Further research should be mos syndrome with colonic atresia. Indian J pedi- tertiary-care hospital. Here at Ziauddin Hospital with history of the same malformation 6. The exact conducted to help provide treatment to such atr.2008;75:189-91 ultrasound was requested which revealed; a single etiology is unknown, and it is believed that most of parents. 2. Adnan AS, Sorath NS. Fraser Syndrome – Case live fetus corresponding to gestational age of 32±2 the anomalies are due to defects in programmed Report. JCPSP.2015;25:S124-S126 weeks breech presentation with an amniotic fluid cell death and apoptosis as well as in metabolism of 3. Vogel MJ, Van Zon P, Brueton L, Gijzen M, Van Tuil index (AFI) of 2.3 cm. Umbilical artery Doppler retinoid 7. The manifestation of autosomal recessive MC, Cox P, Schanze D, kariminejad A, Ghaderi –Sohi showed normal indices. Previous prenatal disorders occurs when the affected child receives S, Blair E et al. Mutations in GRIP1 cause Fraser ultrasound could not be documented due to the abnormal genes for the same trait from both syndrome. J Med Genet. 2012 May;49(5):303-6. unavailability.. In view of her gynecological history a parents. If the individual receives one normal and 4. Slavotinek, A., Li, C., Sherr, E. H., Chudley, A. E. cesarean section was planned. The neonate was a one defective gene, the neonate will only be a Mutation analysis of the FRAS1 gene demonstrates limp male, who did not cry, had no spontaneous carrier and will not show any symptoms. Therefore, new mutations in a propositus with Fraser syndrome. breathing and was bradycardic. He was aggres- the risk of a diseased child is 25% when both parents Am. J. Med Genet. 140A: 1909-1914, 2006. sively resuscitated and intubation was attempted, carry defective genes, 50% of their offspring will be 5. Van Haelst MM, Scambler PJ. Fraser syndrome which was unsuccessful due to severe laryngeal carriers, and 25% will have normal genes. Hence, in collaboration group. Fraser syndrome: a clinical stenosis. Ventilator support was provided with the consanguineous marriages, there is more risk of the study of 59 cases and evaluation of diagnostic assistance of a neonatal laryngeal mask. same defective genes and the subsequent transfer criteria. Am J Med Genet A2007;143:3194-203. to their children. 6. Fraser Syndrome- Review Article. DoveMed. com. Gross examination revealed a male baby weighing 8,2015(http://www.dovemed.com/fraser-syn- 1.5 kg. Craniofacial examination revealed left In our case, the patient has suffered from the same drome/) cryptophthalmos with an eye ball palpable disorder thrice. The literature reviews suggest that 7. Hambire SD, Bhavsar PP. Meenakshi B. Jayakar AV. beneath. His right eye had a narrow palpebral consanguinity is in 15–24% of cases and the recur- Freser-crypthalmos syndrome with cardiovascular fissure and normal eyeball but a deformed pinna. rence rate among siblings is 25% 8. malformations: A rare case. Indian Pediatr. Besides these findings, he had bilateral syndactyly, 2003;888-90. laryngeal stenosis, multiple skeletal defects and Fraser syndrome can be diagnosed by ultrasound 8. Kalaniti K, Sandhya V. Fraser syndrome in three undescended testes. Thus, the diagnosis of Fraser during pregnancy, which may show hyper echoic consecutive siblings. Oman J Ophthalmol. 2011; syndrome was made. Conventional karyo typing lungs, oligohydramnios and microphthalmia. It can 4(2): 87-9. done of both parents, and did not show any chro- also be detected based on the previous pregnancy 9. Leung E, Diaz-Barbosa M, Alabiad C, Hodapp E, mosomal abnormalities. losses owing to still birth, oligohydramnios, and renal Tse D, Murray TG, et al. Pre-natal ultrasonographic agenesis. In our case, the patient received subopti- detection of ophthalmic disease. J Pediatr Opthal- DISCUSSION mal antenatal care and had no ultrasound report mol strabismus 2012;49:26-9 showing any abnormality. Also, her previous history 10. C. Berg, a. Geipel, u. germer, a. pertersen-han- Fraser syndrome was previously known as cryptoph- of fetal loss was not considered as a high risk for any sen*. m. koch-dorfler and u. gembruch. prenatal thalmos syndrome. Later, it was revised and noted genetic disorder. Each time she underwent a cesar- detection of freser sundrome without cryptophthal- that cryptophthalmos may not be a compulsory ean section and hysterectomy, it affected her mos: case report and review of the literature. INTRODUCTION feature. It can be caused by a homozygous or potential chances of conceiving. When the patient ultrasound obstet gynecol 2001; 18:7 CASE REPORT compound heterozygous mutation in the FRAS1 was received, her ultrasound scans identified an AFI The most common organisms causing Infective gene (607830) on chromosome 4q21, the FREM2 of about 2 cm, because of which it was not possible endocarditisis Staphylococcus Aureus. Incidence A case of 24 year old gentleman, known intrave- gene (608945) on chromosome 13q13, or the GRIP1 to identify any anomaly. With the intention to save of IE in intravenous drug abusers is 2 to 4 cases per nous drug abuser, presented with the sudden onset gene (604597) on chromosome 12q14. Therefore, the fetus, a delivery was planned immediately; the 1000 years of intravenous drug abuse.It is more of bilateral visual loss for few hours. No associated INTRODUCTION recessive condition. At least five mutations were 3,4 Fraser syndrome is an optimal term. It is a rare auto- born child had multiple anomalies including common in males (3:1) Another review of 105 ocular symptoms of redness, lacrimation, peri-orbit- identified in the FRAS1 gene, which encodes a somal recessive disorder with variable expressivity 4. syndactyly, cryptophthalmos and laryngeal atresia. patients of infective endocarditis in intravenous al pain, headache, diplopia or proptosis were Fraser syndrome is a clinical condition that affects putative extracellular matrix protein 3. As an autoso- In 1986, Thomas et al established major and minor Even after resuscitation efforts, it was not possible to drug abuser at a tertiary care hospital in Vancouver, found. There was no history of visual impairment in multiple organs. The fetus or newborn has a very mal recessive disorder, this condition should only criteria to diagnose Fraser syndrome. It was modi- save the child. A subsequent diagnosis of Fraser revealed that 86% involve right side, while 14% had the past. He was having high grade, intermittent poor survival rate. The major malformation includes occur when defective genes are inherited from 5 fied by Van Haelstetal.5 in 2007 as; Major criteria syndrome was made. It is imperative that the left sided involvement. Septic embolization is a fever for 3 weeks. Fever was associated with joints an eye defect called cryptophthalmos, which is both parents. 1 were Syndactyly, Cryptophthalmos spectrum, mother receives adequate antenatal care, includ- common complication of IE. Visual complications pain and there was also significant pain at the tips present in 93% of cases. Syndactyly is present in 54% Urinary tract abnormalities, Ambiguous genitalia, ing an ultrasound scan in early pregnancy 9. Other due to micro-embolization and staphylococcal of his fingers. He denied any history of rash or oral of cases. Other defects include urinary anomalies, CASE REPORT Laryngeal and tracheal anomalies, Positive family symptoms like syndactyly, ear and facial abnormali- bacteremia are common in patients with infective ulcers. laryngeal stenosis or displacement, along with 2 history. The minor criteria were Anorectal defects, ties can also be found on an ultrasound. Therefore, endocarditis. We present a case of young, intrave- skeletal deformities 1. The main causes of death are Our patient was a 20-year-old female, married for Dysplastic ears, Skull ossification defects, Umbilical in the case of oligohydramnios, fluid instillation in nous drug abuser with vision loss. In our case, the On examination, his temperature was 100 degree laryngeal atresia and renal agenesis. four years to her first cousin. Both parents were abnormalities, Nasal anomalies. amniotic cavity can be considered to improve the likely cause of vision impairment is microemboliza- Fahrenheit, heart rate 110 beats/minute & regular, healthy with no family history of any known abnor- visualization of the kidney, face, ears, and limbs 10. tion of bacteria in the basilar artery, leading to Respiratory rate 18 breaths/minute, Blood pressure: The incidence is 0.043 per 10,000 live-born infants malities. She was in her third pregnancy, para 1+1, Diagnosis of Fraser syndrome is based on either 3 vasospasm of posterior circulation.Early reversibility 110/70 mm Hg. His general physical examination and 1.1 in 10,000 stillbirths, making it a rare syndrome referred from rural area with 34 weeks of gestational major criteria, 2 major and 2 minor criteria, or 1 In conclusion, Fraser syndrome is a lethal genetic is due to appropriate administration of antibiotics. revealed Osler’s nodes(tender lesions found on 2. About 15% of cases were born to consanguineous amenorrhea, along with severe oligohydramnios. In major and 3 minor criteria. disorder with a poor prognosis. Currently, there are partners, which is a sign that this is an Autosomal her previous pregnancies also, she sought antena-

PAKISTAN JOURNAL OF MEDICINE AND DENTISTRY 2017, VOL. 6 (03) 43

tal care from a local rural hospital. In first pregnan- According to the revised Fraser syndrome criteria, no specific methods to prevent this condition, but Figure 1 & 2: show multiple gross malformations. cy, there was oligohydramnios delivered at 30 our findings in this case, and based on previous genetic testing may help to identify families at risk. Including anopthalmia, dysmorphic face and limb weeks of gestation, the hospital report indicates pregnancy outcomes our patient fulfills the criteria defects. (Parents of the newborn had given written limb defects and anophthalmia, child died immedi- of Fraser syndrome. Couple, who have diagnosis of Fraser syndrome at consent to take the pictures shown above) ately after birth. In second pregnancy, the parents first pregnancy, should have genetic counseling. opted for a termination at 20 weeks due to inade- There is no difference in incidence of Fraser Mother with Fraser syndrome neonatal history REFERENCES quate amniotic fluid. In the recent pregnancy, they syndrome in female and male children. Some racial should be kept on critical prenatal ultrasound received regular antenatal care at local Hospital, predisposition has been observed, as it seems to be checking that may be helpful for diagnosis during 1. Narang M, Kumar M, Shah D. Fraser-crypthohthal- but due to oligohydramnios, she was referred to a more common in gypsy families as well as in families early pregnancy. Further research should be mos syndrome with colonic atresia. Indian J pedi- tertiary-care hospital. Here at Ziauddin Hospital with history of the same malformation 6. The exact conducted to help provide treatment to such atr.2008;75:189-91 ultrasound was requested which revealed; a single etiology is unknown, and it is believed that most of parents. 2. Adnan AS, Sorath NS. Fraser Syndrome – Case live fetus corresponding to gestational age of 32±2 the anomalies are due to defects in programmed Report. JCPSP.2015;25:S124-S126 weeks breech presentation with an amniotic fluid cell death and apoptosis as well as in metabolism of 3. Vogel MJ, Van Zon P, Brueton L, Gijzen M, Van Tuil index (AFI) of 2.3 cm. Umbilical artery Doppler retinoid 7. The manifestation of autosomal recessive MC, Cox P, Schanze D, kariminejad A, Ghaderi –Sohi showed normal indices. Previous prenatal disorders occurs when the affected child receives S, Blair E et al. Mutations in GRIP1 cause Fraser ultrasound could not be documented due to the abnormal genes for the same trait from both syndrome. J Med Genet. 2012 May;49(5):303-6. unavailability.. In view of her gynecological history a parents. If the individual receives one normal and 4. Slavotinek, A., Li, C., Sherr, E. H., Chudley, A. E. cesarean section was planned. The neonate was a one defective gene, the neonate will only be a Mutation analysis of the FRAS1 gene demonstrates limp male, who did not cry, had no spontaneous carrier and will not show any symptoms. Therefore, new mutations in a propositus with Fraser syndrome. breathing and was bradycardic. He was aggres- the risk of a diseased child is 25% when both parents Am. J. Med Genet. 140A: 1909-1914, 2006. sively resuscitated and intubation was attempted, carry defective genes, 50% of their offspring will be 5. Van Haelst MM, Scambler PJ. Fraser syndrome which was unsuccessful due to severe laryngeal carriers, and 25% will have normal genes. Hence, in collaboration group. Fraser syndrome: a clinical stenosis. Ventilator support was provided with the consanguineous marriages, there is more risk of the study of 59 cases and evaluation of diagnostic assistance of a neonatal laryngeal mask. same defective genes and the subsequent transfer criteria. Am J Med Genet A2007;143:3194-203. to their children. 6. Fraser Syndrome- Review Article. DoveMed. com. Gross examination revealed a male baby weighing 8,2015(http://www.dovemed.com/fraser-syn- 1.5 kg. Craniofacial examination revealed left In our case, the patient has suffered from the same 1 drome/) cryptophthalmos with an eye ball palpable disorder thrice. The literature reviews suggest that 7. Hambire SD, Bhavsar PP. Meenakshi B. Jayakar AV. beneath. His right eye had a narrow palpebral consanguinity is in 15–24% of cases and the recur- Freser-crypthalmos syndrome with cardiovascular fissure and normal eyeball but a deformed pinna. rence rate among siblings is 25% 8. malformations: A rare case. Indian Pediatr. Besides these findings, he had bilateral syndactyly, 2003;888-90. laryngeal stenosis, multiple skeletal defects and Fraser syndrome can be diagnosed by ultrasound 8. Kalaniti K, Sandhya V. Fraser syndrome in three undescended testes. Thus, the diagnosis of Fraser during pregnancy, which may show hyper echoic consecutive siblings. Oman J Ophthalmol. 2011; syndrome was made. Conventional karyo typing lungs, oligohydramnios and microphthalmia. It can 4(2): 87-9. done of both parents, and did not show any chro- also be detected based on the previous pregnancy 9. Leung E, Diaz-Barbosa M, Alabiad C, Hodapp E, mosomal abnormalities. losses owing to still birth, oligohydramnios, and renal Tse D, Murray TG, et al. Pre-natal ultrasonographic agenesis. In our case, the patient received subopti- detection of ophthalmic disease. J Pediatr Opthal- DISCUSSION mal antenatal care and had no ultrasound report mol strabismus 2012;49:26-9 showing any abnormality. Also, her previous history 10. C. Berg, a. Geipel, u. germer, a. pertersen-han- Fraser syndrome was previously known as cryptoph- of fetal loss was not considered as a high risk for any sen*. m. koch-dorfler and u. gembruch. prenatal thalmos syndrome. Later, it was revised and noted genetic disorder. Each time she underwent a cesar- detection of freser sundrome without cryptophthal- that cryptophthalmos may not be a compulsory ean section and hysterectomy, it affected her mos: case report and review of the literature. INTRODUCTION feature. It can be caused by a homozygous or potential chances of conceiving. When the patient ultrasound obstet gynecol 2001; 18:7 CASE REPORT compound heterozygous mutation in the FRAS1 was received, her ultrasound scans identified an AFI The most common organisms causing Infective gene (607830) on chromosome 4q21, the FREM2 of about 2 cm, because of which it was not possible 2 endocarditisis Staphylococcus Aureus. Incidence A case of 24 year old gentleman, known intrave- gene (608945) on chromosome 13q13, or the GRIP1 to identify any anomaly. With the intention to save of IE in intravenous drug abusers is 2 to 4 cases per nous drug abuser, presented with the sudden onset gene (604597) on chromosome 12q14. Therefore, the fetus, a delivery was planned immediately; the 1000 years of intravenous drug abuse.It is more of bilateral visual loss for few hours. No associated INTRODUCTION recessive condition. At least five mutations were 3,4 Fraser syndrome is an optimal term. It is a rare auto- born child had multiple anomalies including common in males (3:1) Another review of 105 ocular symptoms of redness, lacrimation, peri-orbit- identified in the FRAS1 gene, which encodes a somal recessive disorder with variable expressivity 4. syndactyly, cryptophthalmos and laryngeal atresia. patients of infective endocarditis in intravenous al pain, headache, diplopia or proptosis were Fraser syndrome is a clinical condition that affects putative extracellular matrix protein 3. As an autoso- In 1986, Thomas et al established major and minor Even after resuscitation efforts, it was not possible to drug abuser at a tertiary care hospital in Vancouver, found. There was no history of visual impairment in multiple organs. The fetus or newborn has a very mal recessive disorder, this condition should only criteria to diagnose Fraser syndrome. It was modi- save the child. A subsequent diagnosis of Fraser revealed that 86% involve right side, while 14% had the past. He was having high grade, intermittent poor survival rate. The major malformation includes occur when defective genes are inherited from 5 fied by Van Haelstetal.5 in 2007 as; Major criteria syndrome was made. It is imperative that the left sided involvement. Septic embolization is a fever for 3 weeks. Fever was associated with joints an eye defect called cryptophthalmos, which is both parents. 1 were Syndactyly, Cryptophthalmos spectrum, mother receives adequate antenatal care, includ- common complication of IE. Visual complications pain and there was also significant pain at the tips present in 93% of cases. Syndactyly is present in 54% Urinary tract abnormalities, Ambiguous genitalia, ing an ultrasound scan in early pregnancy 9. Other due to micro-embolization and staphylococcal of his fingers. He denied any history of rash or oral of cases. Other defects include urinary anomalies, CASE REPORT Laryngeal and tracheal anomalies, Positive family symptoms like syndactyly, ear and facial abnormali- bacteremia are common in patients with infective ulcers. laryngeal stenosis or displacement, along with 2 history. The minor criteria were Anorectal defects, ties can also be found on an ultrasound. Therefore, endocarditis. We present a case of young, intrave- skeletal deformities 1. The main causes of death are Our patient was a 20-year-old female, married for Dysplastic ears, Skull ossification defects, Umbilical in the case of oligohydramnios, fluid instillation in nous drug abuser with vision loss. In our case, the On examination, his temperature was 100 degree laryngeal atresia and renal agenesis. four years to her first cousin. Both parents were abnormalities, Nasal anomalies. amniotic cavity can be considered to improve the likely cause of vision impairment is microemboliza- Fahrenheit, heart rate 110 beats/minute & regular, healthy with no family history of any known abnor- visualization of the kidney, face, ears, and limbs 10. tion of bacteria in the basilar artery, leading to Respiratory rate 18 breaths/minute, Blood pressure: The incidence is 0.043 per 10,000 live-born infants malities. She was in her third pregnancy, para 1+1, Diagnosis of Fraser syndrome is based on either 3 vasospasm of posterior circulation.Early reversibility 110/70 mm Hg. His general physical examination and 1.1 in 10,000 stillbirths, making it a rare syndrome referred from rural area with 34 weeks of gestational major criteria, 2 major and 2 minor criteria, or 1 In conclusion, Fraser syndrome is a lethal genetic is due to appropriate administration of antibiotics. revealed Osler’s nodes(tender lesions found on 2. About 15% of cases were born to consanguineous amenorrhea, along with severe oligohydramnios. In major and 3 minor criteria. disorder with a poor prognosis. Currently, there are partners, which is a sign that this is an Autosomal her previous pregnancies also, she sought antena-

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