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Four small supernumerary marker chromosomes derived from chromosomes 6, 8, 11 and 12 in a patient with minimal clinical abnormalities: a case report
© Fernández-Toral et al; licensee BioMed Central Ltd. 2010
Received: 29 October 2009
Accepted: 3 August 2010
Published: 3 August 2010
Small supernumerary marker chromosomes are still a problem in cytogenetic diagnostic and genetic counseling. This holds especially true for the rare cases with multiple small supernumerary marker chromosomes. Most such cases are reported to be clinically severely affected due to the chromosomal imbalances induced by the presence of small supernumerary marker chromosomes. Here we report the first case of a patient having four different small supernumerary marker chromosomes which, apart from slight developmental retardation in youth and non-malignant hyperpigmentation, presented no other clinical signs.
Our patient was a 30-year-old Caucasian man, delivered by caesarean section because of macrosomy. At birth he presented with bilateral cryptorchidism but no other birth defects. At age of around two years he showed psychomotor delay and a bilateral convergent strabismus. Later he had slight learning difficulties, with normal social behavior and now lives an independent life as an adult. Apart from hypogenitalism, he has multiple hyperpigmented nevi all over his body, short feet with pes cavus and claw toes. At age of 30 years, cytogenetic and molecular cytogenetic analysis revealed a karyotype of 50,XY,+min(6)(:p11.1-> q11.1:),+min(8)(:p11.1->q11.1:),+min(11)(:p11.11->q11:),+min(12)(:p11.2~12->q10:), leading overall to a small partial trisomy in 12p11.1~12.1.
Including this case, four single case reports are available in the literature with a karyotype 50,XN,+4mar. For prenatally detected multiple small supernumerary marker chromosomes in particular we learn from this case that such a cytogenetic condition may be correlated with a positive clinical outcome.
Multiple small supernumerary marker chromosomes (sSMC) with diverse sSMC derived from different chromosomal origin are rarely reported. According to Liehr , up to now 46 such cases were reported: 33 cases with two different sSMC, four cases each with three or four different sSMC, two each with six and seven sSMC, and one case with five sSMC. Overall, only seven of the 46 cases (= 15%) were reported as without clinical signs (according to Liehr  cases 2-14, 2-17, 2-23, 2-26, 2-29, 3-3 and 7-1).
Patients with multiple sSMC constitute a sub-group of patients with sSMC [2, 3]. Little is known about the formation of sSMC in general [1–3] or about multiple sSMC specifically . As reported previously, chromosomes 6, 3, 5, X, 1, 7, and 12 are over-represented in multiple sSMC compared to their contribution to single sSMC .
Here we report the first case with four sSMC derived from chromosomes 6, 8, 11 and 12, with almost no clinical signs.
Our patient was a 30-year-old Spanish Caucasian man; the third child from healthy and non-consanguineous parents. The first child was a healthy boy and the second child was also a boy who died after two days due to hyaline membrane disease and prematurity. Our patient was delivered by caesarean section after 39 gestational weeks because of macrosomy, with a weight of 4250 g and an Apgar score of three, thus, intensive reanimation was required. Within five hours of life he suffered apnea. He was also hypoglycemic and hypocalcemic, but responded well to treatment without suffering a recurrence. Clinical examination showed bilateral cryptorchidism. During her pregnancy our patient's mother was treated with diazepam towards the end of the pregnancy.
When our patient was 19 months old, his weight and length were two standard deviations below normal. During further development, he showed psychomotor delay and a bilateral convergent strabismus; also he started walking when he was 22 months old. At the age of 10 years, his testes were surgically descended. And at the age of 13 years the strabismus was corrected. At school he had slight learning difficulties, with normal social behavior. He later left studying to become a painter.
Here we report the fourth unusual case with four different sSMC and the 34th case with multiple sSMC. It is the eighth case with no or only minor clinical signs due to the sSMC presence. The only detectable sSMC-related chromosomal imbalance is a small partial trisomy 12p11.2~12.1. According to Liehr  there are several cases with a partial trisomy 12p12 due to an sSMC which were all clinically normal. Thus, this region seems to be a potentially transmittable unbalanced chromosomal abnormality (UBCA) without causing clinical problems (see case 12-O-p11.1/1-1 ). Similar UBCA were recently reported for a multitude of chromosomal regions  and especially for the centromere near regions . Thus, it is not clear if the sSMC have a positive correlation with the observed clinical symptoms.
Moreover, it is interesting that the multiple sSMC derive in the present case from chromosomes 6, 8, 11 and 12. Chromosomes 6 and 12 are over-represented in multiple sSMC cases reported to date compared to their contribution to single sSMC . This might point towards a specific way of formation of multiple sSMC during meiosis .
The present case confirms that multiple sSMC may be correlated with an almost normal clinical outcome. This is especially important for the correct genetic counseling of similar pre-natal cases. Furthermore, a small partial trisomy
12p11.2~12.1 seems to correlate largely to no clinical effects. Finally, involvement of chromosome 6 in sSMC formation seems to be correlated with the tendency of multiple sSMC formation.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Supported in parts by the DFG (LI 820/22-1) and DAAD (D07/00070).
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