SELECTED STUDIES

Deletion of the Short Arm of Chromosome III (3p-)
With and Without Mental Retardation

By Dr. D.S. Krishnamurthy, PhD

In 1963, the famous French cytogeneticist, Prof. Lejeune, reported the first chromosomal deletion syndrome. The affected babies in the neonatal period had a moon-like face, microcephaly, hypertelorism, micrognathia, with a characteristic cat-cry ("Cri du chat") resulting from laryngomalacia with narrow vocal cords and curved epiglottis. These clinical findings were due to a deletion of the short arm of chromosome 5. After this first discovery, other cases were reported, affecting different chromosomes. For example: Wolf Syndrome - due to a deletion of the short arm of chromosome 4 (4p-); Alfi Syndrome - due to a deletion of the short arm of chromosome 9 (9p-); and de Grouchy Syndrome - due to a deletion of the short arm of chromosome 18 (18p-).

Deletion of short-arm of chromosome-III

Aside from the well known deletion syndromes, rarely reported the deletion of the short-arm of chromosome-III (3p- syndrome) is associated with characteristic facial features, growth failure, and mental retardation. Typically, individuals with this syndrome have terminal deletions that result in loss of material from 3p25 to 3pter. Most of the cases with 3p- syndrome are mentally retarded, with varying degrees of developmental problems. However, they are amiable.

Due to its variable expression, it is assumed this disorder is a contiguous gene syndrome with an undefined number of genes contributing to the phenotype. Mental retardation in children with 3p- syndrome can be tested by consulting a psychologist. The degree of psychomotor retardation may correlate with the Chromosome analysis report (Karyotype). Whether the deletion in the child is De Novo deletion or inherited from one of the parents and if there is any other chromosome involved in the structural rearrangement.

* 3p- (p25 -> p ter) is a well delineated syndrome, associated with: major and minor congenital anomalies.
* Congenital heart defects (VSD/AVSD…)
* Developmental delay
* Moderate to severe degree mental retardation –But some patients were placid and amiable.
* Exceptional cases with minimal Mental retardation – depending upon the size of the DELETION SEGMENT (telomeric/subtelomeric region). There is only one interesting case reported in Singapore, with 3p- in mother and child with out any phenotypic effect ? (J Med Genet. 1995 Dec;32(12):994-5).

A terminal deletion of chromosome 3 at p25.3 was observed during prenatal diagnosis. A similar deletion is also present in the phenotypically normal mother. The deletion was confirmed by FISH. The breakpoint is distal to the region responsible for the 3p- syndrome. A normal baby girl was born with no apparent phenotypic abnormalities. As this topic is highly specialized and complicated, those interested in greater detail about such abnormalities are encouraged to visit Borgaonker's catalogue of Chromosomal variations or contact me directly at the email listed below.

Further Readings::

Borgaonkar, D.S. (1997). Chromosomal Variation in Man: A Catalog of Chromosomal Variants and Anomalies, 8th Edition. John Wiley & Sons.

Cargile CB, Goh DL, Goodman BK, Chen XN, Korenberg JR, Semenza GL, Thomas GH. Related Articles, Links Abstract Molecular cytogenetic characterization of a subtle interstitial del(3)(p25.3p26.2) in a patient with deletion 3p syndrome. Am J Med Genet. 2002 Apr 22;109(2):133-8.

Farag, T.I.; Al-Awadi, S.A.; Marafie, M.; Bastaki, L.; Krishna Murthy, D.S. et al. (1993). Clustering of Cri du Chat Syndrome Among Bedouins. Am J Med Genet, 46: 347.

Gardner, R.J.M., Sutherland, G.R.: Chromosome Abnormalities and Genetic Counseling, Oxford Press, 1989.

de Grouchy, Jean and Turleau, C.: Clinical Atlas of Human Chromosomes, John Wiley & Sons, 2nd edition, 1984.

Hand JL, Michels VV, Marinello MJ, Ketterling RP, Jalal SM. Abstract Inherited interstitial deletion of chromosomes 5p and 16q without apparent phenotypic effect: further confirmation. Prenat Diagn. 2000 Feb;20(2):144-8; discussion 149-51.

Kariya S, Aoji K, Akagi H, Fukushima K, Chikumoto E, Ogawa T, Karaki M, Nishizaki K.
Abstract A terminal deletion of the short arm of chromosome 3: karyotype 46, XY, del (3) (p25-pter); a case report and literature review. Int J Pediatr Otorhinolaryngol. 2000 Nov 30;56(1):71-8. Review.

Knight LA, Yong MH, Tan M, Ng IS. Del(3) (p25.3) without phenotypic effect. J Med Genet. 1995 Dec;32(12):994-5. Department of Pathology, Singapore General Hospital.

Lejeune, J.; Lafourcade, J.; Berger, R. et al. (1963). Paris: C.R. Academic Sci. 257: 2098.

Lukusa T, Devriendt K, Fryns JP. Abstract A 3p deletion syndrome in a child with both del(3)(p25-->pter) and dup(17)(q23-->qter). Ann Genet. 1999;42(2):91-4.

Pfeiffer RA, Rauch A, Ulmer R, Beinder E, Trautmann U. Abstract Interstitial deletion del(3)(p12p21) in a malformed child subsequent to paternal paracentric insertion (or intraarm shift) 46,XY, ins(3)(p24.1p12.1p21.31). Ann Genet. 1998;41(1):17-21. Review.

Schwyzer U, Binkert F, Caflisch U, Baumgartner B, Schinzel A. Related Articles, Links Abstract Terminal deletion of the short arm of chromosome 3, del(3pter-p25): a recognizable syndrome. Helv Paediatr Acta. 1987;42(4):309-15.

Tucciarone L, Tomassini A, Colasanti A, Sabbi T, Stella P. Abstract [The follow-up of a child with a syndrome due to partial deletion of chromosome 3 (p25-pter)] Minerva Pediatr. 1999 Jul-Aug;51(7-8):283-8. Review. Italian.

DR. KRISHNA MURTHY MSc. PhD is a consultant cytogeneticist and director of the Cytogenetics and Molecular Cytogenetics Laboratory at the Canadian Specialist Hospital in Dubai, UAE. He has published several research papers in human genetics journals and has attended many international conferences. His email is krishnamurthy@cshdubai.com.