Larsen syndrome - lethal variety
http://www.100md.com
《美国医学杂志》
Department of Pediatrics, JJM Medical College, Davangere, Karnataka, India
Abstract
Larsen syndrome is a condition characterized by generalized defect in collagen formation. Autosomal dominant, autosomal recessive and even sporadic fresh mutations have been reported. Very few cases of lethal variety of Larsen syndrome have been reported in the world. The authors emphasize the importance of recognition of this condition which is often misdiagnosed
Keywords: Larsen syndrome; Lethal variety; Prenatal diagnosis
Larsen syndrome is a disease of generalized defect in collagen formation clinically characterized by multiple joint dislocations and characteristic facial abnormalities, first described in 1950.[1] The syndrome has variable inheritance, and both autosomal dominant and recessive modes of inheritance have been reported with peculiar features assigned to each of them.[2]
A rare lethal form of this disorder is characterized by flat facies, cleft palate, multiple joint dislocations, rhizomelic dwarfism and pulmonary hypoplasia. [3],[4],[5],[6] We report a lethal form of Larsen syndrome in a baby born to a consanguineously married couple.
Case report
A male child was born with a normal delivery to a consanganeously married couple. His birth weight was 2.7 kg, length was 46 cm and head circumference 32 cm. Antenatal scan in the third trimester revealed obstructive uropathy with bilateral hydronephrosis. The parents gave history of previous first trimester abortion. Physical examination revealed flat facies with prominent forehead, depressed nasal bridge and widely-spaced eyes. The child had unilateral cleft lip and palate with small chin Figure1. Neck was short with redundant skin over it and a narrow chest with distended abdomen. Limb abnormalities included bilateral dislocation of hip joints with excessive mobility at knee joints, proximal shortening of upper limbs, small hands with bilateral simian crease and small feet with bilateral club feet Figure2.
The baby had stridor and respiratory distress immediately after birth and died after 5 hr of delivery. This could have been secondary to pulmonary hypoplasia. Infantogram showed narrow bell shaped chest with bilateral dislocations at hip and knee joints and bilateral club feet Figure3. Based on the above clinical features and radiological findings, a diagnosis of lethal form of Larsen syndrome was made and the parents were counselled.
Discussion
Larsen syndrome has variable inheritance. Autosomal dominant, autosomal recessive and even sporadic fresh mutations have been reported.[2] It is a syndrome of multiple joint dislocations (hip, knee and elbow) and characteristic facies (prominent forehead, depressed nasal bridge, widely spaced eyes).[1] The above two abnormalities have been described to be universal to this syndrome.[7] Spine anomalies such as cervical vertebrae hypoplasia, scoliosis, kyphosis, wedge vertebrae, spondylolysis, spina bifida oculta also have been described.[8] Hands show cylindrical fingers, spatulate thumbs and short metacarpals. Feet may have talipes equinovalgus or equinovarus deformity along with short metatarsals. Cardiovascular anomalies include aortic dilatation, atrial septal defect, ventricular septal defect, patent ductus arteriosus, mitral valve prolapse and aneurysms of ductus arteriosus.[9] Abnormal laxity of cartilage in early infancy leading to respiratory difficulties such as bronchomalacia and tracheomalacia are also seen.[2], [10]
Very few cases of lethal variety of Larsen syndrome are reported Chen et al[4] reported 2 isolated cases of lethal form of Larsen syndrome; both of them died after birth with pulmonary insufficiency. The authors characterized the defect as 'collagen fiber dismaturity'. Mostello et al[5] provided the first evidence of recessive inheritance of the lethal variant of Larsen syndrome. Yamaguchi et al[6] reported another case and they speculated that the brain dysplasia, which had been described in previous Larsen like syndrome cases, may have been the result of systemic hypoxic-ischemic insults during the second half of gestation, but they did not rule out genetic factors. In the present case, antenatal scan revealed obstructive uropathy with bilateral hydronephrosis. A similar case was reported by Kurtoglu et al[11] with infantile type polycystic kidney disease, billiary dysgenesis and osteosclerosis in a severe form of Larsen syndrome. A bilateral cleft lip and palate was noted in the index case, which has been rarely reported in the available literature.[3]
Preferentially, a targeted antenatal ultrasonographic examination to look for the joint dislocations, facial anomalies, clubfoot etc.,[12],[13] will give a choice to parents whether to continue with pregnancy as well as help decide upon the management of such pregnancies. Many cases of Larsen syndrome are wrongly diagnosed as "arthrochalasis" or "arthrogryposis";[2] recognition of this syndrome is essential for genetic counseling, which helps in reducing the chances of parents having another baby with Larsen syndrome.
References
1. Larsen LJ, Schottstaedt ER, Bost FC. Multiple congenital dislocations associated with characteristic facial abnormality J Pediatr 1950; 37: 574-581.
2. Latta RJ, Graham CB, Aase J, Scham SM, Smith DW. Larsen's syndrome : A skeletal dysplasia with multiple joint dislocations and unusual facies. J Pediatr 1971; 78: 291-298.
3. Clayton SJ, Donnai D. A further patient with the lethal type of Larsen syndrome. J Med Genet 1988; 25: 499-500.
4. Chen H, Chang CH, Perrin E, Perrin J. A lethal, Larsen-like multiple joint dislocation syndrome. Am J Med Genet 1982; 13: 149-161.
5. Mostello D, Hoechstetter L, Bendon RW, Dignan PSJ, Oestreich AE, Siddiqi TA. Prenatal diagnosis of recurrent Larsen syndrome: further definition of a lethal variant. Prenatal Diag 1991; 11 : 215-225.
6. Yamaguchi K, Ogawa Y, Handa T. Brain dysplasia associated with Larsen like syndrome. Pediatr Neurol 1996; 14: 75-79.
7. Sathy N, Krishnamoorthy KM. Larsen syndrome with cardiac anomaly. Indian Pediatr 1992; 29: 783-785.
8. Bowen JR, Ortega K, Ray S, MacEwen GD. Spinal deformities in Larsen syndrome. Clin Orthop 1985; 197: 159-163.
9. Kiel EA, Frias JL, Victorica BE. Cardiovascular manifestation in the Larsen syndrome . Pediatrics 1983; 71: 942-946.
10. Rock MJ, Green CG, Pauli RM, Peters ME. Tracheomalacia and bronchomalacia associated with Larsen syndrome. Pediatr Pulmonol 1988; 5: 55-59.
11. Kurtoglu S, Dundar M, Hallac IK, Uzum K, Okumus Y, Oktem T. Polycystic kidney disease, biliary dysgenesis in a patient with Larsen syndrome. Clin Genet 1997; 51: 408-411.
12. Rochelson B, Petrikorsky B, Shmoys S. Prenatal diagnosis and obstetric management of Larsen syndrome. Obstet Gynecol 1993; 81 : 845-847.
13. Tonsong T, Wanapirak C, Pongsatha S, Sudasana J. Prenatal sonographic diagnosis of Larsen syndrome. J Ultrasound Med 2000; 19 : 419-421.(Kulkarni ML, Mohammed Zah)
Abstract
Larsen syndrome is a condition characterized by generalized defect in collagen formation. Autosomal dominant, autosomal recessive and even sporadic fresh mutations have been reported. Very few cases of lethal variety of Larsen syndrome have been reported in the world. The authors emphasize the importance of recognition of this condition which is often misdiagnosed
Keywords: Larsen syndrome; Lethal variety; Prenatal diagnosis
Larsen syndrome is a disease of generalized defect in collagen formation clinically characterized by multiple joint dislocations and characteristic facial abnormalities, first described in 1950.[1] The syndrome has variable inheritance, and both autosomal dominant and recessive modes of inheritance have been reported with peculiar features assigned to each of them.[2]
A rare lethal form of this disorder is characterized by flat facies, cleft palate, multiple joint dislocations, rhizomelic dwarfism and pulmonary hypoplasia. [3],[4],[5],[6] We report a lethal form of Larsen syndrome in a baby born to a consanguineously married couple.
Case report
A male child was born with a normal delivery to a consanganeously married couple. His birth weight was 2.7 kg, length was 46 cm and head circumference 32 cm. Antenatal scan in the third trimester revealed obstructive uropathy with bilateral hydronephrosis. The parents gave history of previous first trimester abortion. Physical examination revealed flat facies with prominent forehead, depressed nasal bridge and widely-spaced eyes. The child had unilateral cleft lip and palate with small chin Figure1. Neck was short with redundant skin over it and a narrow chest with distended abdomen. Limb abnormalities included bilateral dislocation of hip joints with excessive mobility at knee joints, proximal shortening of upper limbs, small hands with bilateral simian crease and small feet with bilateral club feet Figure2.
The baby had stridor and respiratory distress immediately after birth and died after 5 hr of delivery. This could have been secondary to pulmonary hypoplasia. Infantogram showed narrow bell shaped chest with bilateral dislocations at hip and knee joints and bilateral club feet Figure3. Based on the above clinical features and radiological findings, a diagnosis of lethal form of Larsen syndrome was made and the parents were counselled.
Discussion
Larsen syndrome has variable inheritance. Autosomal dominant, autosomal recessive and even sporadic fresh mutations have been reported.[2] It is a syndrome of multiple joint dislocations (hip, knee and elbow) and characteristic facies (prominent forehead, depressed nasal bridge, widely spaced eyes).[1] The above two abnormalities have been described to be universal to this syndrome.[7] Spine anomalies such as cervical vertebrae hypoplasia, scoliosis, kyphosis, wedge vertebrae, spondylolysis, spina bifida oculta also have been described.[8] Hands show cylindrical fingers, spatulate thumbs and short metacarpals. Feet may have talipes equinovalgus or equinovarus deformity along with short metatarsals. Cardiovascular anomalies include aortic dilatation, atrial septal defect, ventricular septal defect, patent ductus arteriosus, mitral valve prolapse and aneurysms of ductus arteriosus.[9] Abnormal laxity of cartilage in early infancy leading to respiratory difficulties such as bronchomalacia and tracheomalacia are also seen.[2], [10]
Very few cases of lethal variety of Larsen syndrome are reported Chen et al[4] reported 2 isolated cases of lethal form of Larsen syndrome; both of them died after birth with pulmonary insufficiency. The authors characterized the defect as 'collagen fiber dismaturity'. Mostello et al[5] provided the first evidence of recessive inheritance of the lethal variant of Larsen syndrome. Yamaguchi et al[6] reported another case and they speculated that the brain dysplasia, which had been described in previous Larsen like syndrome cases, may have been the result of systemic hypoxic-ischemic insults during the second half of gestation, but they did not rule out genetic factors. In the present case, antenatal scan revealed obstructive uropathy with bilateral hydronephrosis. A similar case was reported by Kurtoglu et al[11] with infantile type polycystic kidney disease, billiary dysgenesis and osteosclerosis in a severe form of Larsen syndrome. A bilateral cleft lip and palate was noted in the index case, which has been rarely reported in the available literature.[3]
Preferentially, a targeted antenatal ultrasonographic examination to look for the joint dislocations, facial anomalies, clubfoot etc.,[12],[13] will give a choice to parents whether to continue with pregnancy as well as help decide upon the management of such pregnancies. Many cases of Larsen syndrome are wrongly diagnosed as "arthrochalasis" or "arthrogryposis";[2] recognition of this syndrome is essential for genetic counseling, which helps in reducing the chances of parents having another baby with Larsen syndrome.
References
1. Larsen LJ, Schottstaedt ER, Bost FC. Multiple congenital dislocations associated with characteristic facial abnormality J Pediatr 1950; 37: 574-581.
2. Latta RJ, Graham CB, Aase J, Scham SM, Smith DW. Larsen's syndrome : A skeletal dysplasia with multiple joint dislocations and unusual facies. J Pediatr 1971; 78: 291-298.
3. Clayton SJ, Donnai D. A further patient with the lethal type of Larsen syndrome. J Med Genet 1988; 25: 499-500.
4. Chen H, Chang CH, Perrin E, Perrin J. A lethal, Larsen-like multiple joint dislocation syndrome. Am J Med Genet 1982; 13: 149-161.
5. Mostello D, Hoechstetter L, Bendon RW, Dignan PSJ, Oestreich AE, Siddiqi TA. Prenatal diagnosis of recurrent Larsen syndrome: further definition of a lethal variant. Prenatal Diag 1991; 11 : 215-225.
6. Yamaguchi K, Ogawa Y, Handa T. Brain dysplasia associated with Larsen like syndrome. Pediatr Neurol 1996; 14: 75-79.
7. Sathy N, Krishnamoorthy KM. Larsen syndrome with cardiac anomaly. Indian Pediatr 1992; 29: 783-785.
8. Bowen JR, Ortega K, Ray S, MacEwen GD. Spinal deformities in Larsen syndrome. Clin Orthop 1985; 197: 159-163.
9. Kiel EA, Frias JL, Victorica BE. Cardiovascular manifestation in the Larsen syndrome . Pediatrics 1983; 71: 942-946.
10. Rock MJ, Green CG, Pauli RM, Peters ME. Tracheomalacia and bronchomalacia associated with Larsen syndrome. Pediatr Pulmonol 1988; 5: 55-59.
11. Kurtoglu S, Dundar M, Hallac IK, Uzum K, Okumus Y, Oktem T. Polycystic kidney disease, biliary dysgenesis in a patient with Larsen syndrome. Clin Genet 1997; 51: 408-411.
12. Rochelson B, Petrikorsky B, Shmoys S. Prenatal diagnosis and obstetric management of Larsen syndrome. Obstet Gynecol 1993; 81 : 845-847.
13. Tonsong T, Wanapirak C, Pongsatha S, Sudasana J. Prenatal sonographic diagnosis of Larsen syndrome. J Ultrasound Med 2000; 19 : 419-421.(Kulkarni ML, Mohammed Zah)