Paediatrics: Common chromosomal disorders

Common chromosomal disorders

Down syndrome

Klinefelter syndrome (47, XXY)

•   Affects 71/600–1/800 boys.

•   Majority caused by non-disjunction during maternal oogenesis.

•   Boys with Klinefelter syndrome enter puberty normally, but by mid-puberty the testes begin to involute and the boys develop hypergonadotrophic hypogonadism with decreased testosterone production (often tall and may develop feminine body build). Testes are small in adult life and men with Klinefelter syndrome are generally infertile (azoospermia). Gynaecomastia develops at puberty in 50%. Boys with Klinefelter syndrome typically have an IQ 715 points lower than their siblings.

•   Many boys with Klinefelter syndrome remain undiagnosed throughout childhood, with the diagnosis only coming to light during investigation of infertility.

•   Diagnosis is by chromosome analysis.

Patau syndrome (trisomy 13)

•   Incidence is 71/6000 births.

•   775% caused by non-disjunction during maternal oogenesis; 720% Robertsonian translocation; 75% result from mosaicism.

•   Trisomy 13 is usually diagnosed by antenatal US scan, since the majority of affected babies have multiple congenital anomalies.

•   Typical malformations include: holoprosencephaly; SGA; microcephalic; microphthalmia; cleft lip/palate; congenital heart disease (e.g. ASD or VSD); renal anomalies (e.g. fused kidneys); postaxial polydactyly; together with severe/profound mental retardation.

•   If there is clinical suspicion of trisomy 13, a senior paediatrician should discuss their concerns with the parents.

•   The diagnosis is confirmed by a chromosome analysis (additional chromosome 13). Most cytogenetics laboratories are able to offer a rapid analysis, e.g. interphase FISH, to confirm the diagnosis quickly.

Edwards’ syndrome (trisomy 18)

•   Incidence is 71/8000 births.

·  Majority caused by non-disjunction during maternal oogenesis.

•   Babies with trisomy 18 are usually SGA (mean birth weight 2240g) with an OFC <3rd centile. Other common features include: congenital heart disease, usually VSD +/– valve dysplasia; short sternum; overriding fingers; ‘rocker-bottom’ feet. There is a strong female excess. Median life expectancy is 74 days, although some affected babies live for several months.

•   If there is clinical suspicion of trisomy 18, a senior paediatrician should discuss their concerns with the parents.

Initial rapid interphase FISH testing followed by formal chromosome analysis (additional chromosome 18).