Yunis varon syndrome
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《美国医学杂志》
Department of pediatrics, JJM Medical College, Davangere, Karnataka, India
Abstract
In this communication is reported a neonate with Yunis Varon syndrome, a rare autosomal recessive disorder, born to a consanguineously married couple who had microcephaly, wide cranial sutures, prominent eyes, hypertelorism, dysplastic ears, sparse hairs, cupid bow like upper lip with median pseudocleft and labio-gingival retraction. Bilateral hypoplasia of thumbs, absent great toes, short phalanges were other features. Additional features in this case included median pseudocleft unreported earlier and C.T. findings of underdeveloped gyri, ischemic changes in temperoparietal region and bilateral lacunar infarcts in middle cerebral artery territory.
Keywords: Cleidocranialdysplasia; Distal aphalangea; Yunis-Varon syndrome (YVS)
Yunis Varon syndrome is an extremely rare autosomal recessive inherited multisystem disorder with defects affecting the skeletal, ectodermal and cardiorespiratory system. The striking characteristics are prenatal and postnatal growth deficiency, defective growth of bones of the skull, along with complete or partial absence of clavicles (cleidocranialdysplasia), characteristic facial features, hypoplasia or absence of thumbs and big toes and distal aphalangea. The first case was reported relatively recently in 1980 by Yunis et al[1] Since then less than 15 cases have been reported from different parts of the world.
Here is reported a 3-day-old child with typical phenotypic features and radiologic features of YVS, alongwith additional features like median pseudo cleft of upper lip and CT findings of underdeveloped gyri, ischemic changes in temporoparietal region and bilateral lacunar infarcts in MCA territory.
Case Report
A 3 day old female child with dysmorphic features was brought to the hospital by anxious grandparents for genetic counselling as there was recurrence in the family. The child was the second child born to a healthy consanguineously married couple. The mother was 22 year old gravida 2, with no antenatal history of polyhydramnios or history suggestive of intrauterine infection like fever, rash or 'flue like' illness. Birth events were normal. The parents confirmed that the previous sibling had features similar to the index (propositus) and expired on ninth day of life.
On examination the baby was short statured and dysmorphic Figure1, her weight was 2.5 Kg and length 45 cm and a head circumference was 28.5 cm, US to LS ratio 1.9:1.
The child had microcephaly, soft skull, wide anterior and posterior fontanelle. Eyes were prominent, and other features noticed were hypertelorism, dysplastic ears, sparse hairs, absent eyelashes and eyebrows, thin lower lip, narrow high arched palate, glossoptosis, cupid bow like upper lip with median pseudocleft and labiogingival retraction Figure2.
There was bilateral hypoplasia of thumb. Fingers were short and tapering. In the lower limbs great toes were absent and nails were hypoplastic. The skin over the neck was loose and joints were lax with generalized hypotonia and genitals were normal. Systemic examination was essentially normal.
Radiological examination revealed absence of first metacarpal bone and distal aphalangea of both hands and feet Figure3. Clavicles were hypoplastic typically on left side. The long bones were slender. With these typical features, the diagnosis of YVS was made. Echocardiogram was normal. CT scan of head revealed microcephaly, wide separated sutures, features of bilateral MCA lacunar infarcts, ischemic changes in temporo parietal region and underdeveloped gyri.
Discussion
Yunis Varon syndrome is a relatively recently described syndrome. It was first described in 1980 by Emilio Yunis and Humbuto Varon in five children from three Colombian families. The patients had multiple malformations, including cleidocranial dysostosis, micrognathia, absent thumbs and distal phalanges of fingers, hypoplasia of proximal phalanx and absence of distal phalanx of the big toes, pelvic dysplasia, bilateral hip dislocation and retracted and poorly deliniated lips. All died before the age of 10 weeks. Because of parental consanguinity and affection of both sexes the author suggested autosomal recessive inheritance.[1] The facial features of the present case were strikingly similar to these cases but had additional feature of median pseudocleft, not described earlier.
Hughes and Partington proposed the designation "the syndrome of Yunis and Varon".[2] Subsequently only few case reports numbering approximately fifteen have been reported.[3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]
Pfeiffer et al (1988) described a patient with consanguineous parents and emphasized aplasia of the thumbs and great toes as an outstanding feature.[3] Rabe and colleagues reported two affected sisters from a German family, one sister had severe hearing impairment and pyloric stenosis, features not previously described in the syndrome.[8] In some patients additional abnormalities have been described such as atrophy of left lobe of liver and anomalies of hepatic vessels,[9] congenital heart disease,[5] hypodontia, cardiomyopathy,[14] osteodysplasty,[6] spinal defects,[7] CNS defects (Aplasia of corpus callosum, arhinencephaly, hamartomatous lesion of the lateral ventricles, cerebellar hypoplasia, hydrocephalus).[11],[16] In the present case CT scan showed features of bilateral MCA lacunar infarcts, ischemic changes in temporo-parietal region and underdeveloped gyri.
Walch et al[11] reported a 15 week female infant with YVS with microcephaly, hydrocephalus and Dandy Walker malformation and hypertension. Qualitatively abnormal bands for oligosaccharides and neuraminic acid were seen on urine analysis by thin layer chromatography. Autopsy showed prominent intraneuronal inclusions with vacuolar degeneration mainly in the thalamic nuclei, dentate nuclei, cerebellar cortex and inferior olivary nuclei. Severe neurologic impairment associated with intraneuronal inclusions and vacuolar degeneration has been taken as evidence for a lysosomal storage disorder.[11]
Prognosis is uniformly poor, only three of the 13 patients survived the first year of life.[2],[5],[14] Two of the three survivors developed severe physical and mental retardation,[2],[5] one patient showed growth retardation with normal intelligence but this child had only few characteristics of the Yunis Varon syndrome.[14]
References
1. Yunis E, Varon H. Cleidocranial dysostois severe micrognathism bilateral absence of thumbs and first metatarsal bone and distal aphalangia : A new genetic syndrome. Am J Dis Child 1980; 134: 649-653.
2. Hughes HE, Partington MW. Brief clinical report : the syndrome of Yunis and Varon - report of a further case. Am J Med Genet 1983; 14: 539-544.
3. Pfeiffer RA, Diekmann L, Stock HJ. Aplasia of the thumbs and great toes as the outstanding features of Yunis and Varon syndrome. A new entity. A new observation. Ann Genet 1988; 31: 241-243.
4. Hennekam RCM, Vermeulen MC. Further delineation of the Yunis-Varon syndrome. J Med Genet 1989; 26: 55-58.
5. Ades LC, Moris LL, Richardson M, Pearson C and Haan EA. Congenital heart malformation in Yunis-Varon syndromes. J Med Genet 1993; 30: 788-792.
6. Garret C, Berry AC, Simpson RH and Hall CM. Yunis Varon syndrome with severe osteodysplasty. J Med Genet 1990; 27: 114-121.
7. Lapeer GL, Fansman SL. Hypodontia, impacted permanent teeth, spinal defects and cardiomegaly in a previously diagnosed case of the Yunis-Varon syndrome. Oral Surg Oral Med Oral Pathol 1992; 73 : 456-460.
8. Rabe H, Brune T, Rossi R, Steinhorst V, Jorch G, Horst J, Wittwer B. Yunis Varon syndrome : the first case of German origin. Clin Dysmorphol 1996; 5 : 217-222.
9. Christie J, Sacks S, Decorato D, Bergasa NV. Atrophy of the left lobe of the liver and anomalous hepatic vessel in a patient with Yunis-Varon syndrome. J Clin Gastroenterol 1999; 29: 210-211.
10. Jones KL. Smith's Recognizable Patterns of Human Malformation. 5th edition. Philadelphia. WB Saunders company . 1997; 410-411.
11. Walch E, Schmidt M, Brennes RE, Emons D, Dame C, Pontz B. Yunis Varon syndrome evidence for a lysoromal storage disease. Am J Med Genet 2000; 95: 157-160.
12. Dworzak F, Mora M, Borroni C, Cornelio F, Blasevich F, Capellini A et al. Generalized lysosomal storage in Yunis Varon syndrome. Neuromuscul Disord 1995; 5 : 423-428.
13. Oyer LE, Tatevoysants NG, Cortez SC, Homstein A, Wallad M. Cleidocranial dysplasia with neonatal death due to central nervous system injury in utero : case report literature review. Pediatr Dev Pathol 1998; 1: 314-318.
14. Partington MW. Cardiomyopathy added to the Yunis Varon syndrome. Proc Greenwood Genet 1988; 7: 224-225.
15. Bhatia S, Holla RG. Yunis-Varon Syndrome. Indian Pediatr 2005; 42: 373-375.
16. Garrett C, Berry AC, Simpson RH, Hall CM. Yunis-Varon Syndrome In Donnai D. Winter RM eds. Congenital Malformation Syndromes . edn. London; Chapman and Hall, 1995; 206-217.(Kulkarni ML, Vani HN, Nag)
Abstract
In this communication is reported a neonate with Yunis Varon syndrome, a rare autosomal recessive disorder, born to a consanguineously married couple who had microcephaly, wide cranial sutures, prominent eyes, hypertelorism, dysplastic ears, sparse hairs, cupid bow like upper lip with median pseudocleft and labio-gingival retraction. Bilateral hypoplasia of thumbs, absent great toes, short phalanges were other features. Additional features in this case included median pseudocleft unreported earlier and C.T. findings of underdeveloped gyri, ischemic changes in temperoparietal region and bilateral lacunar infarcts in middle cerebral artery territory.
Keywords: Cleidocranialdysplasia; Distal aphalangea; Yunis-Varon syndrome (YVS)
Yunis Varon syndrome is an extremely rare autosomal recessive inherited multisystem disorder with defects affecting the skeletal, ectodermal and cardiorespiratory system. The striking characteristics are prenatal and postnatal growth deficiency, defective growth of bones of the skull, along with complete or partial absence of clavicles (cleidocranialdysplasia), characteristic facial features, hypoplasia or absence of thumbs and big toes and distal aphalangea. The first case was reported relatively recently in 1980 by Yunis et al[1] Since then less than 15 cases have been reported from different parts of the world.
Here is reported a 3-day-old child with typical phenotypic features and radiologic features of YVS, alongwith additional features like median pseudo cleft of upper lip and CT findings of underdeveloped gyri, ischemic changes in temporoparietal region and bilateral lacunar infarcts in MCA territory.
Case Report
A 3 day old female child with dysmorphic features was brought to the hospital by anxious grandparents for genetic counselling as there was recurrence in the family. The child was the second child born to a healthy consanguineously married couple. The mother was 22 year old gravida 2, with no antenatal history of polyhydramnios or history suggestive of intrauterine infection like fever, rash or 'flue like' illness. Birth events were normal. The parents confirmed that the previous sibling had features similar to the index (propositus) and expired on ninth day of life.
On examination the baby was short statured and dysmorphic Figure1, her weight was 2.5 Kg and length 45 cm and a head circumference was 28.5 cm, US to LS ratio 1.9:1.
The child had microcephaly, soft skull, wide anterior and posterior fontanelle. Eyes were prominent, and other features noticed were hypertelorism, dysplastic ears, sparse hairs, absent eyelashes and eyebrows, thin lower lip, narrow high arched palate, glossoptosis, cupid bow like upper lip with median pseudocleft and labiogingival retraction Figure2.
There was bilateral hypoplasia of thumb. Fingers were short and tapering. In the lower limbs great toes were absent and nails were hypoplastic. The skin over the neck was loose and joints were lax with generalized hypotonia and genitals were normal. Systemic examination was essentially normal.
Radiological examination revealed absence of first metacarpal bone and distal aphalangea of both hands and feet Figure3. Clavicles were hypoplastic typically on left side. The long bones were slender. With these typical features, the diagnosis of YVS was made. Echocardiogram was normal. CT scan of head revealed microcephaly, wide separated sutures, features of bilateral MCA lacunar infarcts, ischemic changes in temporo parietal region and underdeveloped gyri.
Discussion
Yunis Varon syndrome is a relatively recently described syndrome. It was first described in 1980 by Emilio Yunis and Humbuto Varon in five children from three Colombian families. The patients had multiple malformations, including cleidocranial dysostosis, micrognathia, absent thumbs and distal phalanges of fingers, hypoplasia of proximal phalanx and absence of distal phalanx of the big toes, pelvic dysplasia, bilateral hip dislocation and retracted and poorly deliniated lips. All died before the age of 10 weeks. Because of parental consanguinity and affection of both sexes the author suggested autosomal recessive inheritance.[1] The facial features of the present case were strikingly similar to these cases but had additional feature of median pseudocleft, not described earlier.
Hughes and Partington proposed the designation "the syndrome of Yunis and Varon".[2] Subsequently only few case reports numbering approximately fifteen have been reported.[3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]
Pfeiffer et al (1988) described a patient with consanguineous parents and emphasized aplasia of the thumbs and great toes as an outstanding feature.[3] Rabe and colleagues reported two affected sisters from a German family, one sister had severe hearing impairment and pyloric stenosis, features not previously described in the syndrome.[8] In some patients additional abnormalities have been described such as atrophy of left lobe of liver and anomalies of hepatic vessels,[9] congenital heart disease,[5] hypodontia, cardiomyopathy,[14] osteodysplasty,[6] spinal defects,[7] CNS defects (Aplasia of corpus callosum, arhinencephaly, hamartomatous lesion of the lateral ventricles, cerebellar hypoplasia, hydrocephalus).[11],[16] In the present case CT scan showed features of bilateral MCA lacunar infarcts, ischemic changes in temporo-parietal region and underdeveloped gyri.
Walch et al[11] reported a 15 week female infant with YVS with microcephaly, hydrocephalus and Dandy Walker malformation and hypertension. Qualitatively abnormal bands for oligosaccharides and neuraminic acid were seen on urine analysis by thin layer chromatography. Autopsy showed prominent intraneuronal inclusions with vacuolar degeneration mainly in the thalamic nuclei, dentate nuclei, cerebellar cortex and inferior olivary nuclei. Severe neurologic impairment associated with intraneuronal inclusions and vacuolar degeneration has been taken as evidence for a lysosomal storage disorder.[11]
Prognosis is uniformly poor, only three of the 13 patients survived the first year of life.[2],[5],[14] Two of the three survivors developed severe physical and mental retardation,[2],[5] one patient showed growth retardation with normal intelligence but this child had only few characteristics of the Yunis Varon syndrome.[14]
References
1. Yunis E, Varon H. Cleidocranial dysostois severe micrognathism bilateral absence of thumbs and first metatarsal bone and distal aphalangia : A new genetic syndrome. Am J Dis Child 1980; 134: 649-653.
2. Hughes HE, Partington MW. Brief clinical report : the syndrome of Yunis and Varon - report of a further case. Am J Med Genet 1983; 14: 539-544.
3. Pfeiffer RA, Diekmann L, Stock HJ. Aplasia of the thumbs and great toes as the outstanding features of Yunis and Varon syndrome. A new entity. A new observation. Ann Genet 1988; 31: 241-243.
4. Hennekam RCM, Vermeulen MC. Further delineation of the Yunis-Varon syndrome. J Med Genet 1989; 26: 55-58.
5. Ades LC, Moris LL, Richardson M, Pearson C and Haan EA. Congenital heart malformation in Yunis-Varon syndromes. J Med Genet 1993; 30: 788-792.
6. Garret C, Berry AC, Simpson RH and Hall CM. Yunis Varon syndrome with severe osteodysplasty. J Med Genet 1990; 27: 114-121.
7. Lapeer GL, Fansman SL. Hypodontia, impacted permanent teeth, spinal defects and cardiomegaly in a previously diagnosed case of the Yunis-Varon syndrome. Oral Surg Oral Med Oral Pathol 1992; 73 : 456-460.
8. Rabe H, Brune T, Rossi R, Steinhorst V, Jorch G, Horst J, Wittwer B. Yunis Varon syndrome : the first case of German origin. Clin Dysmorphol 1996; 5 : 217-222.
9. Christie J, Sacks S, Decorato D, Bergasa NV. Atrophy of the left lobe of the liver and anomalous hepatic vessel in a patient with Yunis-Varon syndrome. J Clin Gastroenterol 1999; 29: 210-211.
10. Jones KL. Smith's Recognizable Patterns of Human Malformation. 5th edition. Philadelphia. WB Saunders company . 1997; 410-411.
11. Walch E, Schmidt M, Brennes RE, Emons D, Dame C, Pontz B. Yunis Varon syndrome evidence for a lysoromal storage disease. Am J Med Genet 2000; 95: 157-160.
12. Dworzak F, Mora M, Borroni C, Cornelio F, Blasevich F, Capellini A et al. Generalized lysosomal storage in Yunis Varon syndrome. Neuromuscul Disord 1995; 5 : 423-428.
13. Oyer LE, Tatevoysants NG, Cortez SC, Homstein A, Wallad M. Cleidocranial dysplasia with neonatal death due to central nervous system injury in utero : case report literature review. Pediatr Dev Pathol 1998; 1: 314-318.
14. Partington MW. Cardiomyopathy added to the Yunis Varon syndrome. Proc Greenwood Genet 1988; 7: 224-225.
15. Bhatia S, Holla RG. Yunis-Varon Syndrome. Indian Pediatr 2005; 42: 373-375.
16. Garrett C, Berry AC, Simpson RH, Hall CM. Yunis-Varon Syndrome In Donnai D. Winter RM eds. Congenital Malformation Syndromes . edn. London; Chapman and Hall, 1995; 206-217.(Kulkarni ML, Vani HN, Nag)