Endocrine Abstracts

Background: Chimerism, the coexistence of two genetically distinct cell lines within one individual, is likely under-recognised in paediatric endocrinology because low-level donor lines may be blood limited and clinically silent. Discordant genotype and phenotype, especially in twins sharing a placenta, should prompt multi-tissue testing.

Case 1:: We present monochorionic monozygotic IVF twin sisters, now aged 12 years. Twin 1 had antenatal cystic hygroma (resolved), neonatal bilateral pedal lymphoedema and strawberry naevus. Peripheral blood karyotype showed mosaic Turner syndrome [TS] (XX/XO). She has mild TS stigmata (dysmorphic features, conductive hearing loss, visual impairment), autoimmune hypothyroidism (levothyroxine 25 mg), and short stature treated with growth hormone from 3y11m when height -3.07 SDS; now -1.44 SDS. Gonadotropins confirm primary ovarian insufficiency: LH 15 IU/l, FSH 96.6 IU/l, oestradiol <100 pmol/l, AMH <0.1 pmol/l. She is due to commence pubertal induction with oestradiol. Her co twin’s neonatal blood also reported mosaic TS. This was performed as her twin was affected. However, Twin 2 does not have clinical features; her height SDS is -0.42 without growth hormone treatment; she has normal thyroid function; AMH 26.2 pmol/l (ref 3-46.6), LH <0.1 IU/l, FSH 2.3 IU/l, oestradiol <100 pmol/l. In view of the difference in phenotype compared to her genotype, buccal swabs were performed for both twins. Buccal swabs for Quantitative Fluorescence-PCR have confirmed XO in twin 1 and XX in twin 2. Case 2: A 16-month-old reared female was referred to the DSD service following an incidental blood XX/XY finding (indication unknown). Examination showed normal female external genitalia. Buccal swab demonstrated predominantly XX cells with low-level XY, thought to be secondary to lymphocytes within her saliva. Pregnancy was monochorionic diamniotic; male co-twin sadly died in utero at 18 weeks gestation.

Conclusion: We describe two children in whom a blood-restricted chimeric line derived from a co-twin likely explains genotype-phenotype discordance (mosaic TS in an asymptomatic twin; XX/XY blood line in a phenotypic girl). Shared placentation and early twin-to-twin haematogenous exchange are plausible mechanisms. Consider chimerism and multi-site sampling when cytogenetic results do not match phenotype.