Fibrochondrogenesis
http://www.100md.com
《美国医学杂志》
Department of Pediatrics, J.J.M. Medical College, Davangere, Karnataka, India
Abstract
Fibrochondrogenesis is a rare lethal short-limb skeletal dysplasia. Till now only fifteen cases have been reported since Lazzaroni-Fossati first described it in 1978. Hence reported a case of fibrochondrogenesis in a child born to a consanguineously married couple with characteristic physical and radiological features and discuss the incidence, inheritence, ultrasonographic, clinical, radiological and pathological characteristics of this disorder.
Keywords: Fibrochondrogenesis; Lethal skeletal dysplasia; Autosomal recessive
Fibrochondrogenesis is a distinct, neonatally lethal short-limb skeletal dysplasia characterised by a distinctive facial appearance and specific radiological changes.[1] It is considered to be inherited as an autosomal recessive disorder.[2],[3] A histologic study of growing cartilage shows fibrosis of the cartilage.[4] This condition was first described by Lazzaroni-Fossati in France in 1978.[4] Till date only fifteen cases are reported.[2] To the best of our knowledge no case of fibrochondrogenesis has been reported from India.
Case Report
A single, live, term, 3 kg male baby was delivered via naturalis by forceps delivery through thick meconium stained amniotic fluid. Baby had birth asphyxia and needed resuscitation. He was admitted to NICU for respiratory distress, which started at first hour of life. He was the first child born to a consanguineously married couple (uncle-niece). The antenatal period was uneventful. On examination, a one hour old male baby was found in respiratory distress with short limbed dwarfism. Anthropometric measurements were: length 39cm (<5 centile), head circumference 37cm (>95 centile), chest circumference 30cm, upper segment 24.5cm, lower segment 14.5 cm, with ratio of US/LS: 1.68/1 and arm span of 31.5 cm.
Physical abnormalities noted in him were short stature and macrocephaly Figure1. Facial features included hypertelorism, flat nasal bridge, short neck, low set small crumpled ears, prominent philtrum, small mouth and micrognathia Figure2. Limbs showed rhizomelic shortening, simian crease, hypoplastic finger and toe nails. Cardiovascular system examination was clinically normal. Abdominal examination showed moderate hepatosplenomegaly. Central nervous system was clinically normal. The child was in respiratory distress with respiratory rate of 60/min.
Radiological features in this case included long clavicle, narrow chest, short rib with cupping, flat vertebrae, short thickened long bones, rhizomelic shortening, dumbbell shaped femora, short fibulae, hypoplastic iliac bones, flat acetabulae, broad hypoplastic ischii, dislocation of elbow and hip joint. Figure3 and Figure4. On 2nd day of admission baby succumbed to respiratory distress.
Discussion
Fibrochondrogenesis was first described by Lazzaroni-Fossati in 1978.[4] Since then it has been reported from different countries like Spain[5], UAE[3], Germany[6], Japan[7], Switzerland[2] but none from India.
A study conducted in UAE showed 9.46/10,000 births had some type of skeletal dysplasia, in an inbred high risk population, out of which 4.7/10,000 births were of autosomal recessive type. For them the most common recessive type of dysplasia was fibrochondrogenesis with 1.05/10,000 births followed by chondrodysplasia punctata 0.78/10,000 births.[8] Another study in Germany showed an incidence of 1-3/10,000 births for lethal chondrodysplasias.[6]
Fibrochondrogenesis has been reported in twins at 24 weeks of gestation.[9] Two studies report its occurrence in siblings in a consanguineous couple, which confirms autosomal recessive inheritance of fibrochondrogenesis.[2],[3] The risk of recurrence is 25% and accurate diagnosis is necessary to enable genetic counselling.[10]
Fibrochondrogenesis has been diagnosed prenatally using ultrasonography. Ultrasound findings of this condition are intrauterine growth retardation, apparently large head, hypoplasia of thorax, prominent abdomen, rhizomelic limbs, wide metaphysis.[11] Youngest case reported is a 17-week fetus with micrognathia and bifid tongue which author opines that this has extended the phenotype of this rare condition.[12]
Histology of the growth plate cartilage shows abnormal organization of type II collagen.[13] It is grossly disorganized and has a dense fibrous collagenous matrix. Diaphyseal and metaphyseal trabecular bones are found to be normal.[14] Cartilage has unique interwoven fibrous septae and fibroblastic degeneration of chondrocytes.[15]
The characteristic features of this condition are short stature, widely open anterior fontanalle, sutures, protuberant eyes with large cornea, flat nasal bridge, anteverted nares, cleft palate, short neck, lowset malformed ears, small chest and omphalocele. Limbs show rhizomelic shortening, camptodactyly, fifth finger clinodactyly, hypoplastic finger and toe nails.
Radiological findings are flattened vertebrae with posterior vertebral hypoplasia and saggital midline cleft. Some authors report vertebrae to be pear shaped[15]. short thin ribs with anterior and posterior cupping, long thin clavicles, small chest, short dumbbell shaped long bones[14] with broad irregular metaphyses and prominent metaphyseal spurs. Other characters include short fibulae, hypoplastic ovoid ilia, irregular, flattened acetabula with metaphyseal spikes, narrow sacrosciatic notches and broad hypoplastic ischii.[16] The present case had majority of the radiological findings described except for vertebral midline cleft, vertebral hypoplasia and metaphyseal spurs. Almost all authors have stressed upon wide metaphyses which is present in the present case and is a major differentiating feature from other skeletal dysplasias.
References
1. Al Gazali LI, Bakalinova D, Bakir M, Dawodu A. Fibrochondrogenesis: Clinical and radiological feature. Clin Dysmorphol 1997; 6: 157-163.
2. Leeners B, Funk A, Cotarelo CL, Savur I. Two sibs with fibrochondrogenesis. Am J Med Genet 2004; 127(A): 318-320.
3. Al Gazali LI, Bkir M, Dawodu A, Haas D. Recurrence of fibrochondrogenesis in a consanguineous family. Clin Dysmorphol 1999; 8: 59-61.
4. Lazzaroni Fossati, Stanescu V, Stanescu R, Serra G, Magliano P, Marotcaux P. Fibrochondrogenesis. Arch Fr Pediatr 1978; 35: 1096-1104.
5. Martinez Frias ML, Garcia A, Luevas J, Rodriguez JI, Urioste M. A new case of fibrochondrogenesis from Spain. J Med Genet 1996; 33: 429-431.
6. Saver I, Klein B, Leener B, Cotarelo C, Heyl W, Funk A. Letale osteochondrodysplasien: Pranatale and postnatale differential diagnostik. Ultraschall Med 2000; 21: 112-121.
7. Nishimora G. Fibrochondrogenesis. Ryoiukibetsu Shokogun Shirizu 2001; 33: 712-713.
8. Al Gazali LI, Bakir MN, Hamid Z, Varady E, Varghes M, Haas D et al. Birth prevalence and pattern of osteochondrodysplasia in an inbred high risk population. Birth Defects Res Part A Clin Mol Teratol 2003; 67: 125-132.
9. Bankier A, Fortune D, Duke J, Sillence DO. Fibrochondrogenesis in male twins at 24 weeks gestation. Am J Med Genet 1991; 38: 95-98.
10. Randrianaivo H, Haddad G, Roman H, Lise A, Toutain A, Le Merer M et al. Fetal fibrochondrogenesis at 26 weeks gestation Prenat Diagnosis 2002; 22: 806-810.
11. Migarbane A, Haddad S, Berijaoui L. Prenatal ultrasonography: clinical and radiological findings in a boy with fibrochondrogenesis. Am J Perinatol 1998; 15: 403-407.
12. Hunt NC, Vujanic GM. Fibrochondrogenesis in a 17 week fetus: a case expanding the phenotype. Am J Med Genet 1998; 75: 326-329.
13. Stanecu V, Stanescu R, Pathogenic mechanisms in osteochondrodysplasias. J Bone Joint Surg Am 1984; 66: 817-836.
14. Eteson DT, Adomian GE, Orony A, Koide T, Sagiura Y, Calabro A et al. Fibrochondrogenesis: radiologic and histologic studies. Am J Med Genet 1984; 19: 277-290.
15. Whitley CB, Langer LO Jr, Ophoven J, Gilbert EF, Gonzalez CH, Mammel M et al. Fibrochondrogenesis: lethal autosomal recessive chondrodysplasia with distinctive cartilage histopathology. Am J Med Genet 1984; 19: 265-275.
16. Jones KL, ed. Smith's Recognizable Patterns of Human Malformations . 5th edn. Philadelphia; W.B. Saunders, 1997; 330-331.(Kulkarni ML, Matadh Praka)
Abstract
Fibrochondrogenesis is a rare lethal short-limb skeletal dysplasia. Till now only fifteen cases have been reported since Lazzaroni-Fossati first described it in 1978. Hence reported a case of fibrochondrogenesis in a child born to a consanguineously married couple with characteristic physical and radiological features and discuss the incidence, inheritence, ultrasonographic, clinical, radiological and pathological characteristics of this disorder.
Keywords: Fibrochondrogenesis; Lethal skeletal dysplasia; Autosomal recessive
Fibrochondrogenesis is a distinct, neonatally lethal short-limb skeletal dysplasia characterised by a distinctive facial appearance and specific radiological changes.[1] It is considered to be inherited as an autosomal recessive disorder.[2],[3] A histologic study of growing cartilage shows fibrosis of the cartilage.[4] This condition was first described by Lazzaroni-Fossati in France in 1978.[4] Till date only fifteen cases are reported.[2] To the best of our knowledge no case of fibrochondrogenesis has been reported from India.
Case Report
A single, live, term, 3 kg male baby was delivered via naturalis by forceps delivery through thick meconium stained amniotic fluid. Baby had birth asphyxia and needed resuscitation. He was admitted to NICU for respiratory distress, which started at first hour of life. He was the first child born to a consanguineously married couple (uncle-niece). The antenatal period was uneventful. On examination, a one hour old male baby was found in respiratory distress with short limbed dwarfism. Anthropometric measurements were: length 39cm (<5 centile), head circumference 37cm (>95 centile), chest circumference 30cm, upper segment 24.5cm, lower segment 14.5 cm, with ratio of US/LS: 1.68/1 and arm span of 31.5 cm.
Physical abnormalities noted in him were short stature and macrocephaly Figure1. Facial features included hypertelorism, flat nasal bridge, short neck, low set small crumpled ears, prominent philtrum, small mouth and micrognathia Figure2. Limbs showed rhizomelic shortening, simian crease, hypoplastic finger and toe nails. Cardiovascular system examination was clinically normal. Abdominal examination showed moderate hepatosplenomegaly. Central nervous system was clinically normal. The child was in respiratory distress with respiratory rate of 60/min.
Radiological features in this case included long clavicle, narrow chest, short rib with cupping, flat vertebrae, short thickened long bones, rhizomelic shortening, dumbbell shaped femora, short fibulae, hypoplastic iliac bones, flat acetabulae, broad hypoplastic ischii, dislocation of elbow and hip joint. Figure3 and Figure4. On 2nd day of admission baby succumbed to respiratory distress.
Discussion
Fibrochondrogenesis was first described by Lazzaroni-Fossati in 1978.[4] Since then it has been reported from different countries like Spain[5], UAE[3], Germany[6], Japan[7], Switzerland[2] but none from India.
A study conducted in UAE showed 9.46/10,000 births had some type of skeletal dysplasia, in an inbred high risk population, out of which 4.7/10,000 births were of autosomal recessive type. For them the most common recessive type of dysplasia was fibrochondrogenesis with 1.05/10,000 births followed by chondrodysplasia punctata 0.78/10,000 births.[8] Another study in Germany showed an incidence of 1-3/10,000 births for lethal chondrodysplasias.[6]
Fibrochondrogenesis has been reported in twins at 24 weeks of gestation.[9] Two studies report its occurrence in siblings in a consanguineous couple, which confirms autosomal recessive inheritance of fibrochondrogenesis.[2],[3] The risk of recurrence is 25% and accurate diagnosis is necessary to enable genetic counselling.[10]
Fibrochondrogenesis has been diagnosed prenatally using ultrasonography. Ultrasound findings of this condition are intrauterine growth retardation, apparently large head, hypoplasia of thorax, prominent abdomen, rhizomelic limbs, wide metaphysis.[11] Youngest case reported is a 17-week fetus with micrognathia and bifid tongue which author opines that this has extended the phenotype of this rare condition.[12]
Histology of the growth plate cartilage shows abnormal organization of type II collagen.[13] It is grossly disorganized and has a dense fibrous collagenous matrix. Diaphyseal and metaphyseal trabecular bones are found to be normal.[14] Cartilage has unique interwoven fibrous septae and fibroblastic degeneration of chondrocytes.[15]
The characteristic features of this condition are short stature, widely open anterior fontanalle, sutures, protuberant eyes with large cornea, flat nasal bridge, anteverted nares, cleft palate, short neck, lowset malformed ears, small chest and omphalocele. Limbs show rhizomelic shortening, camptodactyly, fifth finger clinodactyly, hypoplastic finger and toe nails.
Radiological findings are flattened vertebrae with posterior vertebral hypoplasia and saggital midline cleft. Some authors report vertebrae to be pear shaped[15]. short thin ribs with anterior and posterior cupping, long thin clavicles, small chest, short dumbbell shaped long bones[14] with broad irregular metaphyses and prominent metaphyseal spurs. Other characters include short fibulae, hypoplastic ovoid ilia, irregular, flattened acetabula with metaphyseal spikes, narrow sacrosciatic notches and broad hypoplastic ischii.[16] The present case had majority of the radiological findings described except for vertebral midline cleft, vertebral hypoplasia and metaphyseal spurs. Almost all authors have stressed upon wide metaphyses which is present in the present case and is a major differentiating feature from other skeletal dysplasias.
References
1. Al Gazali LI, Bakalinova D, Bakir M, Dawodu A. Fibrochondrogenesis: Clinical and radiological feature. Clin Dysmorphol 1997; 6: 157-163.
2. Leeners B, Funk A, Cotarelo CL, Savur I. Two sibs with fibrochondrogenesis. Am J Med Genet 2004; 127(A): 318-320.
3. Al Gazali LI, Bkir M, Dawodu A, Haas D. Recurrence of fibrochondrogenesis in a consanguineous family. Clin Dysmorphol 1999; 8: 59-61.
4. Lazzaroni Fossati, Stanescu V, Stanescu R, Serra G, Magliano P, Marotcaux P. Fibrochondrogenesis. Arch Fr Pediatr 1978; 35: 1096-1104.
5. Martinez Frias ML, Garcia A, Luevas J, Rodriguez JI, Urioste M. A new case of fibrochondrogenesis from Spain. J Med Genet 1996; 33: 429-431.
6. Saver I, Klein B, Leener B, Cotarelo C, Heyl W, Funk A. Letale osteochondrodysplasien: Pranatale and postnatale differential diagnostik. Ultraschall Med 2000; 21: 112-121.
7. Nishimora G. Fibrochondrogenesis. Ryoiukibetsu Shokogun Shirizu 2001; 33: 712-713.
8. Al Gazali LI, Bakir MN, Hamid Z, Varady E, Varghes M, Haas D et al. Birth prevalence and pattern of osteochondrodysplasia in an inbred high risk population. Birth Defects Res Part A Clin Mol Teratol 2003; 67: 125-132.
9. Bankier A, Fortune D, Duke J, Sillence DO. Fibrochondrogenesis in male twins at 24 weeks gestation. Am J Med Genet 1991; 38: 95-98.
10. Randrianaivo H, Haddad G, Roman H, Lise A, Toutain A, Le Merer M et al. Fetal fibrochondrogenesis at 26 weeks gestation Prenat Diagnosis 2002; 22: 806-810.
11. Migarbane A, Haddad S, Berijaoui L. Prenatal ultrasonography: clinical and radiological findings in a boy with fibrochondrogenesis. Am J Perinatol 1998; 15: 403-407.
12. Hunt NC, Vujanic GM. Fibrochondrogenesis in a 17 week fetus: a case expanding the phenotype. Am J Med Genet 1998; 75: 326-329.
13. Stanecu V, Stanescu R, Pathogenic mechanisms in osteochondrodysplasias. J Bone Joint Surg Am 1984; 66: 817-836.
14. Eteson DT, Adomian GE, Orony A, Koide T, Sagiura Y, Calabro A et al. Fibrochondrogenesis: radiologic and histologic studies. Am J Med Genet 1984; 19: 277-290.
15. Whitley CB, Langer LO Jr, Ophoven J, Gilbert EF, Gonzalez CH, Mammel M et al. Fibrochondrogenesis: lethal autosomal recessive chondrodysplasia with distinctive cartilage histopathology. Am J Med Genet 1984; 19: 265-275.
16. Jones KL, ed. Smith's Recognizable Patterns of Human Malformations . 5th edn. Philadelphia; W.B. Saunders, 1997; 330-331.(Kulkarni ML, Matadh Praka)