Autosomal dominant syndrome resembling Coffin–Siris syndrome

Abstract

Coffin-Siris syndrome is a multiple congenital anomaly/mental retardation syndrome with phenotypic variability [OMIM 135900]. The diagnosis is based solely on clinical findings, as there is currently no molecular, biochemical, or cytogenetic analysis available to confirm a diagnosis. Although typically described as an autosomal recessive disorder, autosomal dominant inheritance has also been infrequently reported. We describe a mother and her two daughters who all have features that resemble Coffin-Siris syndrome. However, this is not a completely convincing diagnosis given that hypertelorism is not a feature of Coffin-Siris syndrome and the family is relatively mildly affected. Yet, this family provides further evidence of an autosomal dominant mode of inheritance for a likely variant of Coffin-Siris syndrome (at least in some families). In addition, Sibling 1 had premature thelarche. She is the second reported individual within the spectrum of Coffin-Siris syndrome to have premature thelarche, indicating that it may be a rare clinical feature.

The Coffin–Siris syndrome: A proposed diagnostic approach and assessment of 15 overlapping cases

“…This familial presentation could be consistent with autosomal recessive inheritance, which has been previously proposed [Haspeslagh et al, 1984; Bonioli et al, 1995; Flynn and Milunsky, 2006]. Single-nucleotide polymorphism (SNP) 550K array analysis of this family demonstrated a 758kb de novo duplication on chromosome 3p26.3 in the proband not seen in the other affected children.…”

“…Candidate genes in this shared region included Ubiquitin-protein ligase E3B (UBE3B) although sequencing of UBE3B revealed no mutations. Of note, this pattern of an affected paternal cousin could also demonstrate autosomal dominant inheritance with reduced penetrance, as has previously proposed as well [Flynn and Milunsky, 2006]. …”

“…[Patel et al, 1987; McPherson et al, 1997; McGhee et al, 2000]. Furthermore, both autosomal dominant [Flynn and Milunsky, 2006; Haspeslagh et al, 1984] and autosomal recessive [Bonioli et al, 1995; Flynn and Milunsky, 2006] modes of transmission have been proposed. Six literature reports describe familial cases [Carey and Hall, 1978; Franceschini et al, 1986; Flynn and Milunsky, 2006; Bonioli et al, 1995; Kirel et al, 2000; Haspeslagh et al, 1984].…”

“…Furthermore, both autosomal dominant [Flynn and Milunsky, 2006; Haspeslagh et al, 1984] and autosomal recessive [Bonioli et al, 1995; Flynn and Milunsky, 2006] modes of transmission have been proposed. Six literature reports describe familial cases [Carey and Hall, 1978; Franceschini et al, 1986; Flynn and Milunsky, 2006; Bonioli et al, 1995; Kirel et al, 2000; Haspeslagh et al, 1984]. A previous report of what was described as Coffin-Lowry syndrome now appears to be regarded as likely Coffin-Siris syndrome, involving two affected sisters and displaying a possible autosomal recessive inheritance pattern [Mattei et al, 1981].…”

Is this the Coffin–Siris syndrome or the BOD syndrome?

“…Both autosomal recessive [Franceschini et al, 1986;Bonioli et al, 1995;Ounap et al, 1998] and autosomal dominant inheritance [Elliott and Teebi, 2000;Flynn and Milunsky, 2006] have been postulated or described. There is evidence pointing towards the 7q32-q34 chromosomal region as being associated with this syndrome.…”