Short case report 163
Broadening the spectrum of Catania brachydactylous type of acrofacial dysostoses Rafael L. Aguirre-Guilléna,d, Rodolfo Santoyo-Duranb, Rodrigo Tapia-Hernándezb, Cesáreo González-Bernalb, Enrique A. Tostado-Rabagob, Marisol Díaz-Silvac, Diana L. Valero-Rodríguezb, E. Lizbeth Mellín-Sánchezd and J. Román Corona-Riverad,e Clinical Dysmorphology 2015, 24:163–165 a
b
c
Service of Genetics, Neonatology, Audiology, Esperanza Lopez-Mateos Maternity and Infant Hospital, Health Secretary, Government of Jalisco, dCenter for Registry and Research in Congenital Anomalies (CRIAC), Service of Genetics, Pediatric Division, Dr Juan I. Menchaca Civil Hospital of Guadalajara and e Dr Enrique Corona Rivera Institute of Human Genetics, Department of Molecular Biology and Genomics, Health Sciences University Centre, University of Guadalajara, Guadalajara, Jalisco, Mexico
Correspondence to Rafael L. Aguirre-Guillén, MD, Service of Genetics, Esperanza Lopez-Mateos Maternity and Infant Hospital, Health Secretary, Government of Jalisco, Av. Constituyentes 1075, Col. Moderna, Guadalajara, 44100 Jalisco, Mexico Tel: + 52 33 3619 0635 x146; e-mail: [email protected] Received 11 May 2014 Accepted 7 April 2015
Key features
Investigations
Micrognathia Brachydactyly Spinal dysraphism Downslanting palpebral fissures
The echocardiogram was normal; renal ultrasound reported right ectasia secondary to a neurogenic bladder. Cytogenetic analysis at the 550-band level showed a 46, XX karyotype. MRI of the brain and spinal cord indicated hypoplasia of the corpus callosum, cortical atrophy predominantly in the frontal region, cerebellar vermis hypoplasia, large cisterna magna Dandy–Walker like, syringomyelia, spina bifida occulta at the level of the fourth to fifth lumbar vertebrae, and tethered cord. Radiographs of the spine and extremities showed thoracolumbar scoliosis, protruding sacrum, shortened bilateral fourth and fifth metacarpal bones, and hypoplasia of the middle and distal phalanges of the fifth fingers. Brainstem auditory-evoked potentials were performed and reported as showing moderate to severe hearing loss.
Clinical summary The proposita was born of a 17-year-old primigravida mother and a 19-year-old father, both healthy. Family history did not indicate any malformations, abortions, nor consanguinity. There was no exposure to known teratogens during pregnancy. The female was born at 39 weeks’ gestation by vaginal delivery with a birth weight of 2310 g (fifth centile), length of 40 cm (below fifth centile), and head circumference of 32 cm (10th centile). Apgar scores were 8 and 8 at 1 and 5 min, respectively. At birth, the baby was noted to have severe generalized hypotonia, a weak cry, and absence of sucking reflex. Physical examination of the craniofacial region indicated a double posterior parietal swirl, a wide forehead, a triangular face, sparse eyebrows, short downslanting palpebral fissures, telecanthus, flat malar region, a prominent nasal bridge, a large nose, long philtrum, a narrow mouth, micrognathia, a short and webbed neck, low-set and posteriorly rotated ears, and a low posterior hairline. In the hands and feet, the metacarpals appeared short, the fifth fingers were also short with clinodactyly, and there were single palmar creases; bilateral varus club foot deformity was noted. In the lumbosacral region, there was a boney mass with palpable dysraphism. At 2 months of age, physical examination indicated a weight of 3200 g (− 3.69 SD), a length of 46 cm (− 4.97 SD), and occipitofrontal circumference of 36 cm (− 1.92 SD). New observations included severe bilateral palpebral ptosis and a deep philtrum (Fig. 1). At 5 months of age, the patient died because of asphyxiation caused by food aspiration (Fig. 2). 0962-8827 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Fig. 1
Proposita. (a) Frontal image: broad forehead, ptosis, short downslanting palpebral fissures, a prominent nose, deep philtrum, micrognathia, and a webbed neck. (b) Side view: low-set posterior rotated ear, micrognathia, and short neck.
DOI: 10.1097/MCD.0000000000000089
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
164 Clinical Dysmorphology
2015, Vol 24 No 4
Fig. 2
(a, b) Front and side view: short downslanting palpebral fissures, prominent nose, micrognathia, and ear anomalies. (c, e) Radiographs of the right and left hands; fifth finger brachydactyly. (d) Webbed neck, lumbar bone mass protruding, and bilateral varus talipes. (f) Frontal cortical atrophy, hypoplasia of corpus callosum, and hypoplastic cerebellum. (g) Tethered cord.
Discussion The acrofacial dysostoses (AFD) are a heterogeneous group combining limb abnormalities with mandibulofacial dysostosis. The limb anomalies in AFD can be preaxial type such as Nager syndrome; postaxial such as Miller syndrome; and others where syndromic entities are broad (Wieczorek, 2013). There is a report of a Sicilian family case with facial dysostoses, a mother and four children, whose main characteristics were microcephaly, intellectual disability, short stature, brachydactyly of fingers, dental anomalies, ear anomalies, downward-slanting palpebral fissures, micrognathia, and malar hypoplasia. This entity was named Catania brachydactylous type of AFD (Opitz et al., 1993). A similar phenotype was reported in a mother and daughter whose principal findings were malar hypoplasia, ear anomalies, downward-slanting palpebral
fissures, dental anomalies, and brachydactyly. They were considered as the second reported family with Catania syndrome (Wulfsberg et al., 1996). In the differential diagnosis are Frias and craniofacioskeletal syndromes. The main features of the Frias syndrome are growth deficiency, facial anomalies, ptosis of the eyelids, hypertelorism, downslanting palpebral fissures, micrognathia, ear anomalies, and brachydactyly (Martínez-Frías et al., 2005). Microcephaly, short stature, brachydactyly, and mild impairment of cognitive function are the main characteristics in craniofacioskeletal syndrome (Stevenson et al., 2007). Catania syndrome presents exclusive findings such as webbed neck, spina bifida occulta, and hair anomalies. We consider that the manifestations found in our patient are consistent with the findings reported in the previous patients with AFD Catania type (Table 1).
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
A case report of Catania syndrome Aguirre-Guillén et al. 165
Phenotypes of Catania type of acrofacial dysostosis compared with our index case
Table 1
Finding Short stature Intellectual disability Intrauterine growth retardation Microcephaly Hair anomalies High forehead Palpebral fissures slant down Malar hypoplasia Sparse lateral eyebrows High arched palate Widow’s peak Small or ‘dysplastic’ ears Micrognathia Dental caries Webbed neck Brachydactyly Short fifth finger Clinodactyly of fifth finger Short thumb Interdigital webbing Single palmar crease Cryptorchidism Hypospadias Inguinal hernia Spina bifida occulta
Opitz et al. (1993)
Wulfsberg et al. (1996)
Proposita
Total
5/5 5/5 2/4
2/2 2/2 2/2
+ + +
8/8 8/8 5/7
3/4 4/5 5/5 4/5
2/2 0/2 0/2 1/2
− + + +
5/6 5/8 6/8 6/8
5/5 2/2 3/3 5/5 5/5 4/4 3/3 2/5 5/5 5/5 1/3
2/2 1/2 2/2 1/2 2/2 0/2 1/2 0/2 2/2 2/2 1/2
+ + + − + + NA + + + +
8/8 3/5 6/6 6/8 8/8 5/7 4/5 3/8 8/8 8/8 3/6
4/4 4/4 5/5 3/4 1/4 2/5 1/5
1/2 1/2 0/2 NA NA 0/2 0/2
− − + NA NA − +
5/7 5/7 6/8 3/4 1/4 2/8 2/8
NA, not available.
The genes responsible for many AFD are not defined, although there is emerging evidence that mutations in genes encoding elements of the spliceosome can be implicated
(Wieczorek, 2013). The strong relationship between the development of the facial structures and limb development is well-known (Winter, 1996). A failure in the development of neural crest cells can cause abnormalities in the development of craniofacial structures and central nervous system such as spina bifida occult, tethered cord, and cortical atrophy (Strobl-Mazzulla et al., 2012) as observed in our index case. The AFD syndromes have a wide phenotypic variability, but distinct subgroups are now being defined and our proposita further defines the Catania brachydactylous type.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References Martínez-Frías ML, Toral JF, López-Grondona F, Mendioroz J, Bermejo E (2005). Growth deficiency, facial anomalies, and brachydactyly (Frías syndrome): a second family. Am J Med Genet A 137A:288–291. Opitz JM, Mollica F, Sorge G, Milana G, Cimino G, Caltabiano M (1993). Acrofacial dysostoses: review and report of a previously undescribed condition: the autosomal or X-linked dominant Catania form of acrofacial dysostosis. Am J Med Genet 47:660–678. Stevenson RE, Brasington CK, Skinner C, Simensen RJ, Spence JE, Kesler S, et al. (2007). Craniofacioskeletal syndrome: an X-linked dominant disorder with early lethality in males. Am J Med Genet A 143A:2321–2329. Strobl-Mazzulla PH, Marini M, Buzzi A (2012). Epigenetic landscape and miRNA involvement during neural crest development. Dev Dyn 241:1849–1856. Wieczorek D (2013). Human facial dysostoses. Clin Genet 83:499–510. Winter RM (1996). What’s in a face? Nat Genet 2:124–129. Wulfsberg EA, Campbell AB, Lurie IW, Eanet KR (1996). Confirmation of the Catania brachydactylous type of acrofacial dysostosis: report of a second family. Am J Med Genet 63:554–557.
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Broadening the spectrum of Catania brachydactylous type of acrofacial dysostoses Rafael L. Aguirre-Guilléna,d, Rodolfo Santoyo-Duranb, Rodrigo Tapia-Hernándezb, Cesáreo González-Bernalb, Enrique A. Tostado-Rabagob, Marisol Díaz-Silvac, Diana L. Valero-Rodríguezb, E. Lizbeth Mellín-Sánchezd and J. Román Corona-Riverad,e Clinical Dysmorphology 2015, 24:163–165 a
b
c
Service of Genetics, Neonatology, Audiology, Esperanza Lopez-Mateos Maternity and Infant Hospital, Health Secretary, Government of Jalisco, dCenter for Registry and Research in Congenital Anomalies (CRIAC), Service of Genetics, Pediatric Division, Dr Juan I. Menchaca Civil Hospital of Guadalajara and e Dr Enrique Corona Rivera Institute of Human Genetics, Department of Molecular Biology and Genomics, Health Sciences University Centre, University of Guadalajara, Guadalajara, Jalisco, Mexico
Correspondence to Rafael L. Aguirre-Guillén, MD, Service of Genetics, Esperanza Lopez-Mateos Maternity and Infant Hospital, Health Secretary, Government of Jalisco, Av. Constituyentes 1075, Col. Moderna, Guadalajara, 44100 Jalisco, Mexico Tel: + 52 33 3619 0635 x146; e-mail: [email protected] Received 11 May 2014 Accepted 7 April 2015
Key features
Investigations
Micrognathia Brachydactyly Spinal dysraphism Downslanting palpebral fissures
The echocardiogram was normal; renal ultrasound reported right ectasia secondary to a neurogenic bladder. Cytogenetic analysis at the 550-band level showed a 46, XX karyotype. MRI of the brain and spinal cord indicated hypoplasia of the corpus callosum, cortical atrophy predominantly in the frontal region, cerebellar vermis hypoplasia, large cisterna magna Dandy–Walker like, syringomyelia, spina bifida occulta at the level of the fourth to fifth lumbar vertebrae, and tethered cord. Radiographs of the spine and extremities showed thoracolumbar scoliosis, protruding sacrum, shortened bilateral fourth and fifth metacarpal bones, and hypoplasia of the middle and distal phalanges of the fifth fingers. Brainstem auditory-evoked potentials were performed and reported as showing moderate to severe hearing loss.
Clinical summary The proposita was born of a 17-year-old primigravida mother and a 19-year-old father, both healthy. Family history did not indicate any malformations, abortions, nor consanguinity. There was no exposure to known teratogens during pregnancy. The female was born at 39 weeks’ gestation by vaginal delivery with a birth weight of 2310 g (fifth centile), length of 40 cm (below fifth centile), and head circumference of 32 cm (10th centile). Apgar scores were 8 and 8 at 1 and 5 min, respectively. At birth, the baby was noted to have severe generalized hypotonia, a weak cry, and absence of sucking reflex. Physical examination of the craniofacial region indicated a double posterior parietal swirl, a wide forehead, a triangular face, sparse eyebrows, short downslanting palpebral fissures, telecanthus, flat malar region, a prominent nasal bridge, a large nose, long philtrum, a narrow mouth, micrognathia, a short and webbed neck, low-set and posteriorly rotated ears, and a low posterior hairline. In the hands and feet, the metacarpals appeared short, the fifth fingers were also short with clinodactyly, and there were single palmar creases; bilateral varus club foot deformity was noted. In the lumbosacral region, there was a boney mass with palpable dysraphism. At 2 months of age, physical examination indicated a weight of 3200 g (− 3.69 SD), a length of 46 cm (− 4.97 SD), and occipitofrontal circumference of 36 cm (− 1.92 SD). New observations included severe bilateral palpebral ptosis and a deep philtrum (Fig. 1). At 5 months of age, the patient died because of asphyxiation caused by food aspiration (Fig. 2). 0962-8827 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Fig. 1
Proposita. (a) Frontal image: broad forehead, ptosis, short downslanting palpebral fissures, a prominent nose, deep philtrum, micrognathia, and a webbed neck. (b) Side view: low-set posterior rotated ear, micrognathia, and short neck.
DOI: 10.1097/MCD.0000000000000089
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
164 Clinical Dysmorphology
2015, Vol 24 No 4
Fig. 2
(a, b) Front and side view: short downslanting palpebral fissures, prominent nose, micrognathia, and ear anomalies. (c, e) Radiographs of the right and left hands; fifth finger brachydactyly. (d) Webbed neck, lumbar bone mass protruding, and bilateral varus talipes. (f) Frontal cortical atrophy, hypoplasia of corpus callosum, and hypoplastic cerebellum. (g) Tethered cord.
Discussion The acrofacial dysostoses (AFD) are a heterogeneous group combining limb abnormalities with mandibulofacial dysostosis. The limb anomalies in AFD can be preaxial type such as Nager syndrome; postaxial such as Miller syndrome; and others where syndromic entities are broad (Wieczorek, 2013). There is a report of a Sicilian family case with facial dysostoses, a mother and four children, whose main characteristics were microcephaly, intellectual disability, short stature, brachydactyly of fingers, dental anomalies, ear anomalies, downward-slanting palpebral fissures, micrognathia, and malar hypoplasia. This entity was named Catania brachydactylous type of AFD (Opitz et al., 1993). A similar phenotype was reported in a mother and daughter whose principal findings were malar hypoplasia, ear anomalies, downward-slanting palpebral
fissures, dental anomalies, and brachydactyly. They were considered as the second reported family with Catania syndrome (Wulfsberg et al., 1996). In the differential diagnosis are Frias and craniofacioskeletal syndromes. The main features of the Frias syndrome are growth deficiency, facial anomalies, ptosis of the eyelids, hypertelorism, downslanting palpebral fissures, micrognathia, ear anomalies, and brachydactyly (Martínez-Frías et al., 2005). Microcephaly, short stature, brachydactyly, and mild impairment of cognitive function are the main characteristics in craniofacioskeletal syndrome (Stevenson et al., 2007). Catania syndrome presents exclusive findings such as webbed neck, spina bifida occulta, and hair anomalies. We consider that the manifestations found in our patient are consistent with the findings reported in the previous patients with AFD Catania type (Table 1).
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
A case report of Catania syndrome Aguirre-Guillén et al. 165
Phenotypes of Catania type of acrofacial dysostosis compared with our index case
Table 1
Finding Short stature Intellectual disability Intrauterine growth retardation Microcephaly Hair anomalies High forehead Palpebral fissures slant down Malar hypoplasia Sparse lateral eyebrows High arched palate Widow’s peak Small or ‘dysplastic’ ears Micrognathia Dental caries Webbed neck Brachydactyly Short fifth finger Clinodactyly of fifth finger Short thumb Interdigital webbing Single palmar crease Cryptorchidism Hypospadias Inguinal hernia Spina bifida occulta
Opitz et al. (1993)
Wulfsberg et al. (1996)
Proposita
Total
5/5 5/5 2/4
2/2 2/2 2/2
+ + +
8/8 8/8 5/7
3/4 4/5 5/5 4/5
2/2 0/2 0/2 1/2
− + + +
5/6 5/8 6/8 6/8
5/5 2/2 3/3 5/5 5/5 4/4 3/3 2/5 5/5 5/5 1/3
2/2 1/2 2/2 1/2 2/2 0/2 1/2 0/2 2/2 2/2 1/2
+ + + − + + NA + + + +
8/8 3/5 6/6 6/8 8/8 5/7 4/5 3/8 8/8 8/8 3/6
4/4 4/4 5/5 3/4 1/4 2/5 1/5
1/2 1/2 0/2 NA NA 0/2 0/2
− − + NA NA − +
5/7 5/7 6/8 3/4 1/4 2/8 2/8
NA, not available.
The genes responsible for many AFD are not defined, although there is emerging evidence that mutations in genes encoding elements of the spliceosome can be implicated
(Wieczorek, 2013). The strong relationship between the development of the facial structures and limb development is well-known (Winter, 1996). A failure in the development of neural crest cells can cause abnormalities in the development of craniofacial structures and central nervous system such as spina bifida occult, tethered cord, and cortical atrophy (Strobl-Mazzulla et al., 2012) as observed in our index case. The AFD syndromes have a wide phenotypic variability, but distinct subgroups are now being defined and our proposita further defines the Catania brachydactylous type.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References Martínez-Frías ML, Toral JF, López-Grondona F, Mendioroz J, Bermejo E (2005). Growth deficiency, facial anomalies, and brachydactyly (Frías syndrome): a second family. Am J Med Genet A 137A:288–291. Opitz JM, Mollica F, Sorge G, Milana G, Cimino G, Caltabiano M (1993). Acrofacial dysostoses: review and report of a previously undescribed condition: the autosomal or X-linked dominant Catania form of acrofacial dysostosis. Am J Med Genet 47:660–678. Stevenson RE, Brasington CK, Skinner C, Simensen RJ, Spence JE, Kesler S, et al. (2007). Craniofacioskeletal syndrome: an X-linked dominant disorder with early lethality in males. Am J Med Genet A 143A:2321–2329. Strobl-Mazzulla PH, Marini M, Buzzi A (2012). Epigenetic landscape and miRNA involvement during neural crest development. Dev Dyn 241:1849–1856. Wieczorek D (2013). Human facial dysostoses. Clin Genet 83:499–510. Winter RM (1996). What’s in a face? Nat Genet 2:124–129. Wulfsberg EA, Campbell AB, Lurie IW, Eanet KR (1996). Confirmation of the Catania brachydactylous type of acrofacial dysostosis: report of a second family. Am J Med Genet 63:554–557.
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
