Entry - 264480 - PSEUDOTRISOMY 13 SYNDROME - OMIM
264480

PSEUDOTRISOMY 13 SYNDROME


Alternative titles; symbols

HOLOPROSENCEPHALY-POLYDACTYLY SYNDROME


Clinical Synopsis
 

INHERITANCE
- Autosomal recessive
HEAD & NECK
Head
- Microcephaly
Face
- Cebocephaly (36%)
Ears
- Low set ears
- Posteriorly rotated ears
Eyes
- Hypotelorism
- Microphthalmia
- Upslanting palpebral fissures
- Cyclopia (5%)
Mouth
- Medial cleft lip and palate (59%)
- Lateral cleft lip
CARDIOVASCULAR
Heart
- Dextrocardia
- Tricuspid atresia
- Ventricular septal defect
- Atrial septal defect
- Coarctation of aorta
- Atrioventricular canal
RESPIRATORY
Lung
- Malsegmentation
CHEST
Ribs Sternum Clavicles & Scapulae
- 11 pairs of ribs
ABDOMEN
External Features
- Omphalocele
Gastrointestinal
- Imperforate anus
GENITOURINARY
External Genitalia (Male)
- Small penis
- Deep scrotal raphe
Internal Genitalia (Male)
- Cryptorchidism
Internal Genitalia (Female)
- Uterine hypoplasia
- Duplicate uterus
- Duplicate vagina
- Bicornuate uterus
Kidneys
- Renal agenesis
- Renal hypoplasia
SKELETAL
Spine
- Hemivertebrae
Hands
- Postaxial polydactyly
Feet
- Postaxial polydactyly
- 2-3 toe syndactyly
NEUROLOGIC
Central Nervous System
- Holoprosencephaly (100%)
- Hydrocephalus
- Cerebellar hypoplasia
- Encephalocele
- Hypotonia
- Polymicrogyria
- Absent corpus callosum
- Absent olfactory tracts and bulbs
ENDOCRINE FEATURES
- Adrenal hypoplasia
LABORATORY ABNORMALITIES
- Normal karyotype
MISCELLANEOUS
- Sex ratio - 2.3 males-to-1 female

TEXT

Clinical Features

Hewitt et al. (1989) reported a fetus with holoprosencephaly and polydactyly and a normal karyotype. They cited 2 similar reports (Young and Madders, 1987; Moerman and Fryns, 1988). Because holoprosencephaly and polydactyly are features of trisomy 13, Hewitt et al. (1989) suggested the designation pseudotrisomy 13.

Cohen and Gorlin (1991) used the term pseudotrisomy 13 syndrome to designate cases of holoprosencephaly, severe facial anomalies, postaxial polydactyly, various other congenital defects, and normal chromosomes. They summarized 11 examples. They concluded that the cases reported by Bachman et al. (1990) were instances of this syndrome and not of the hydrolethalus syndrome (see 236680). The other cases from the literature cited by Bachman et al. (1990) as holoprosencephaly in hydrolethalus syndrome were thought by Cohen and Gorlin (1991) to be in error.

Verloes et al. (1991) observed 5 unrelated children with the syndrome and suggested the designation holoprosencephaly-polydactyly syndrome. They commented on the phenotypic overlap not only with the hydrolethalus syndrome but also with lethal acrodysgenital dwarfism (see Smith-Lemli-Opitz syndrome, 270400).

Hennekam et al. (1991) emphasized the occurrence of heart defect with holoprosencephaly and postaxial polydactyly. They reported male and female sibs, the offspring of second-cousin parents.

Seller et al. (1993) diagnosed prenatally 2 sibs with holoprosencephaly, midface hypoplasia, and normal chromosomes. One of the sibs also had polydactyly.

Ramos-Arroyo et al. (1994) reported the case of a baby with holoprosencephaly, median cleft lip, cardiac and genital anomalies, normal upper limbs, and a normal 46,XX karyotype. This is an instance of uncertainty between variable expression and basic heterogeneity. They reviewed reports of 22 cases of pseudotrisomy 13 syndrome and found postaxial polydactyly in 19 and preaxial polydactyly in 1.

Amor and Woods (2000) described a brother and sister with pseudotrisomy 13. Both had holoprosencephaly, polydactyly, cardiac lesions, and a normal karyotype. The parents were first cousins.


Inheritance

Cohen and Gorlin (1991) noted that 2 pairs of affected sibs (Atkin, 1988; Bachman et al., 1990) and 2 other cases with consanguinity suggested autosomal recessive inheritance. They suggested that alternatively an undetected microdeletion or etiologic heterogeneity, some cases possibly representing dominant new mutations, should be considered.

The 2 affected sibs reported by Seller et al. (1993) and consanguinity in the family reported by Amor and Woods (2000) supported autosomal recessive inheritance.


Cytogenetics

Relevant to this syndrome may be the analysis of Brown et al. (1993) which defined band 13q32 as being associated particularly with major malformations and digital abnormalities. Patients with more distal deletions had severe mental retardation but did not have major malformations or growth retardation.


REFERENCES

  1. Amor, D. J., Woods, C. G. Pseudotrisomy 13 syndrome in siblings. Clin. Dysmorph. 9: 115-118, 2000. [PubMed: 10826623, related citations] [Full Text]

  2. Atkin, J. F. A new syndrome with cyclopia and trisomy 13 features. (Abstract) Am. J. Hum. Genet. 43 (suppl.): A36, 1988.

  3. Bachman, H., Clark, R. D., Salahi, W. Holoprosencephaly and polydactyly: a possible expression of the hydrolethalus syndrome. J. Med. Genet. 27: 50-52, 1990. [PubMed: 2407847, related citations] [Full Text]

  4. Brown, S., Gersen, S., Anyane-Yeboa, K., Warburton, D. Preliminary definition of a 'critical region' of chromosome 13 in q32: report of 14 cases with 13q deletions and review of the literature. Am. J. Med. Genet. 45: 52-59, 1993. [PubMed: 8418661, related citations] [Full Text]

  5. Cohen, M. M., Jr., Gorlin, R. J. Pseudo-trisomy 13 syndrome. Am. J. Med. Genet. 39: 332-335, 1991. [PubMed: 1867286, related citations] [Full Text]

  6. Hennekam, R. C. M., Van Noort, G., De La Fuente, A. A. Familial holoprosencephaly, heart defects, and polydactyly. Am. J. Med. Genet. 41: 258-262, 1991. [PubMed: 1785646, related citations] [Full Text]

  7. Hewitt, B. G., Seller, M. J., Bennett, C. P., Maxwell, D. M. Holoprosencephaly, polydactyly and normal chromosomes: pseudo-trisomy 13? (Letter) Clin. Genet. 36: 141-143, 1989. [PubMed: 2766571, related citations] [Full Text]

  8. Moerman, P., Fryns, J. P. Holoprosencephaly and postaxial polydactyly: another observation. (Letter) J. Med. Genet. 25: 501-504, 1988. [PubMed: 3172147, related citations] [Full Text]

  9. Ramos-Arroyo, M. A., de Miguel, C., Valiente, A., Moreno-Laguna, S. Further delineation of pseudotrisomy 13 syndrome: a case without polydactyly. Am. J. Med. Genet. 50: 177-179, 1994. [PubMed: 8010349, related citations] [Full Text]

  10. Seller, M. J., Chitty, L. S., Dunbar, H. Pseudotrisomy 13 and autosomal recessive holoprosencephaly. J. Med. Genet. 30: 970-971, 1993. [PubMed: 8301659, related citations] [Full Text]

  11. Verloes, A., Ayme, S., Gambarelli, D., Gonzales, M., Le Merrer, M., Mulliez, N., Philip, N., Roume, J. Holoprosencephaly-polydactyly ('pseudotrisomy 13') syndrome: a syndrome with features of hydrolethalus and Smith-Lemli-Opitz syndromes: a collaborative multicentre study. J. Med. Genet. 28: 297-303, 1991. [PubMed: 1865466, related citations] [Full Text]

  12. Young, I. D., Madders, D. J. Unknown syndrome: holoprosencephaly, congenital heart defects, and polydactyly. J. Med. Genet. 24: 714-716, 1987. [PubMed: 3430550, related citations] [Full Text]


Cassandra L. Kniffin - updated : 10/12/2006
Ada Hamosh - updated : 7/10/2000
Creation Date:
Victor A. McKusick : 6/10/1991
alopez : 06/15/2020
wwang : 05/12/2011
terry : 3/13/2009
carol : 3/11/2009
wwang : 10/25/2006
ckniffin : 10/12/2006
carol : 2/3/2005
alopez : 7/11/2000
terry : 7/10/2000
terry : 3/27/1996
mark : 3/14/1996
terry : 2/26/1996
mimadm : 3/12/1994
carol : 12/16/1993
carol : 3/25/1993
carol : 1/25/1993
supermim : 3/17/1992
carol : 12/19/1991

264480

PSEUDOTRISOMY 13 SYNDROME


Alternative titles; symbols

HOLOPROSENCEPHALY-POLYDACTYLY SYNDROME


SNOMEDCT: 716091000;   ORPHA: 2166;  



TEXT

Clinical Features

Hewitt et al. (1989) reported a fetus with holoprosencephaly and polydactyly and a normal karyotype. They cited 2 similar reports (Young and Madders, 1987; Moerman and Fryns, 1988). Because holoprosencephaly and polydactyly are features of trisomy 13, Hewitt et al. (1989) suggested the designation pseudotrisomy 13.

Cohen and Gorlin (1991) used the term pseudotrisomy 13 syndrome to designate cases of holoprosencephaly, severe facial anomalies, postaxial polydactyly, various other congenital defects, and normal chromosomes. They summarized 11 examples. They concluded that the cases reported by Bachman et al. (1990) were instances of this syndrome and not of the hydrolethalus syndrome (see 236680). The other cases from the literature cited by Bachman et al. (1990) as holoprosencephaly in hydrolethalus syndrome were thought by Cohen and Gorlin (1991) to be in error.

Verloes et al. (1991) observed 5 unrelated children with the syndrome and suggested the designation holoprosencephaly-polydactyly syndrome. They commented on the phenotypic overlap not only with the hydrolethalus syndrome but also with lethal acrodysgenital dwarfism (see Smith-Lemli-Opitz syndrome, 270400).

Hennekam et al. (1991) emphasized the occurrence of heart defect with holoprosencephaly and postaxial polydactyly. They reported male and female sibs, the offspring of second-cousin parents.

Seller et al. (1993) diagnosed prenatally 2 sibs with holoprosencephaly, midface hypoplasia, and normal chromosomes. One of the sibs also had polydactyly.

Ramos-Arroyo et al. (1994) reported the case of a baby with holoprosencephaly, median cleft lip, cardiac and genital anomalies, normal upper limbs, and a normal 46,XX karyotype. This is an instance of uncertainty between variable expression and basic heterogeneity. They reviewed reports of 22 cases of pseudotrisomy 13 syndrome and found postaxial polydactyly in 19 and preaxial polydactyly in 1.

Amor and Woods (2000) described a brother and sister with pseudotrisomy 13. Both had holoprosencephaly, polydactyly, cardiac lesions, and a normal karyotype. The parents were first cousins.


Inheritance

Cohen and Gorlin (1991) noted that 2 pairs of affected sibs (Atkin, 1988; Bachman et al., 1990) and 2 other cases with consanguinity suggested autosomal recessive inheritance. They suggested that alternatively an undetected microdeletion or etiologic heterogeneity, some cases possibly representing dominant new mutations, should be considered.

The 2 affected sibs reported by Seller et al. (1993) and consanguinity in the family reported by Amor and Woods (2000) supported autosomal recessive inheritance.


Cytogenetics

Relevant to this syndrome may be the analysis of Brown et al. (1993) which defined band 13q32 as being associated particularly with major malformations and digital abnormalities. Patients with more distal deletions had severe mental retardation but did not have major malformations or growth retardation.


REFERENCES

  1. Amor, D. J., Woods, C. G. Pseudotrisomy 13 syndrome in siblings. Clin. Dysmorph. 9: 115-118, 2000. [PubMed: 10826623] [Full Text: https://doi.org/10.1097/00019605-200009020-00008]

  2. Atkin, J. F. A new syndrome with cyclopia and trisomy 13 features. (Abstract) Am. J. Hum. Genet. 43 (suppl.): A36, 1988.

  3. Bachman, H., Clark, R. D., Salahi, W. Holoprosencephaly and polydactyly: a possible expression of the hydrolethalus syndrome. J. Med. Genet. 27: 50-52, 1990. [PubMed: 2407847] [Full Text: https://doi.org/10.1136/jmg.27.1.50]

  4. Brown, S., Gersen, S., Anyane-Yeboa, K., Warburton, D. Preliminary definition of a 'critical region' of chromosome 13 in q32: report of 14 cases with 13q deletions and review of the literature. Am. J. Med. Genet. 45: 52-59, 1993. [PubMed: 8418661] [Full Text: https://doi.org/10.1002/ajmg.1320450115]

  5. Cohen, M. M., Jr., Gorlin, R. J. Pseudo-trisomy 13 syndrome. Am. J. Med. Genet. 39: 332-335, 1991. [PubMed: 1867286] [Full Text: https://doi.org/10.1002/ajmg.1320390316]

  6. Hennekam, R. C. M., Van Noort, G., De La Fuente, A. A. Familial holoprosencephaly, heart defects, and polydactyly. Am. J. Med. Genet. 41: 258-262, 1991. [PubMed: 1785646] [Full Text: https://doi.org/10.1002/ajmg.1320410226]

  7. Hewitt, B. G., Seller, M. J., Bennett, C. P., Maxwell, D. M. Holoprosencephaly, polydactyly and normal chromosomes: pseudo-trisomy 13? (Letter) Clin. Genet. 36: 141-143, 1989. [PubMed: 2766571] [Full Text: https://doi.org/10.1111/j.1399-0004.1989.tb03177.x]

  8. Moerman, P., Fryns, J. P. Holoprosencephaly and postaxial polydactyly: another observation. (Letter) J. Med. Genet. 25: 501-504, 1988. [PubMed: 3172147] [Full Text: https://doi.org/10.1136/jmg.25.7.501]

  9. Ramos-Arroyo, M. A., de Miguel, C., Valiente, A., Moreno-Laguna, S. Further delineation of pseudotrisomy 13 syndrome: a case without polydactyly. Am. J. Med. Genet. 50: 177-179, 1994. [PubMed: 8010349] [Full Text: https://doi.org/10.1002/ajmg.1320500208]

  10. Seller, M. J., Chitty, L. S., Dunbar, H. Pseudotrisomy 13 and autosomal recessive holoprosencephaly. J. Med. Genet. 30: 970-971, 1993. [PubMed: 8301659] [Full Text: https://doi.org/10.1136/jmg.30.11.970]

  11. Verloes, A., Ayme, S., Gambarelli, D., Gonzales, M., Le Merrer, M., Mulliez, N., Philip, N., Roume, J. Holoprosencephaly-polydactyly ('pseudotrisomy 13') syndrome: a syndrome with features of hydrolethalus and Smith-Lemli-Opitz syndromes: a collaborative multicentre study. J. Med. Genet. 28: 297-303, 1991. [PubMed: 1865466] [Full Text: https://doi.org/10.1136/jmg.28.5.297]

  12. Young, I. D., Madders, D. J. Unknown syndrome: holoprosencephaly, congenital heart defects, and polydactyly. J. Med. Genet. 24: 714-716, 1987. [PubMed: 3430550] [Full Text: https://doi.org/10.1136/jmg.24.11.714]


Contributors:
Cassandra L. Kniffin - updated : 10/12/2006
Ada Hamosh - updated : 7/10/2000

Creation Date:
Victor A. McKusick : 6/10/1991

Edit History:
alopez : 06/15/2020
wwang : 05/12/2011
terry : 3/13/2009
carol : 3/11/2009
wwang : 10/25/2006
ckniffin : 10/12/2006
carol : 2/3/2005
alopez : 7/11/2000
terry : 7/10/2000
terry : 3/27/1996
mark : 3/14/1996
terry : 2/26/1996
mimadm : 3/12/1994
carol : 12/16/1993
carol : 3/25/1993
carol : 1/25/1993
supermim : 3/17/1992
carol : 12/19/1991