ESPE Abstracts

Background: Septo-optic dysplasia (SOD) is a rare congenital anomaly, clinically heterogeneous, combining optic nerve and pituitary gland hypoplasia, midline abnormalities of the brain, including absence of the corpus callosum and septum pellucidum. The diagnosis is made when two or more features of the classic triad are present. HESX1, SOX2, SOX3, FGF8, FGFR1, PROKR1, SHH, are implicated in the etiology of SOD.

Objective and hypotheses: Description of a patient with SOD, negative in the HESX1, SOX2, SOX3 mutational screening.

Method: Case report, direct sequencing of HESX1, SOX2, SOX3, aCGH array.

Results: Girl, born after 1^st uneventful pregnancy, SGA, with jaundice, hypotonia, feeding difficulties as neonate; mild developmental delay during infancy. Referred because of short stature (SDS_h–2.46) at 9.8 years. Diagnosed additionally with: optic nerves and macula hypoplasia, nystagmus, strabismus, absent septum pellucidum, hydrocephalus, anterior pituitary hypoplasia (MRI), growth hormone deficiency (GH peak 1.5 mU/ml after Arg-HCL); start of rhGH and development of central hypothyroidism thereafter, treated by L-T4. A 599 kb deletion 17(q21.31)(44188501-44787179)x1(hg19), containing the pseudogene LOC644246 and the gene KANSL1, known to cause Koolen-de Vries syndrome (KDVS) were found. mental retardation (MR), facial dysmorphism, hypotonia, developmental delay, SGA, short stature, brain and refraction anomalies, strabismus, and hypopituitarism due to PSIS (only one reported case) are described. A 551 kb duplication X(p11.3p11.3)(45838699-46389900)x3(hg19) was also found, including ZNF673, ZNF674 genes. Duplications/deletions are known to cause MR, retinal dystrophy and short stature.

Conclusion: This is the first case of KDVS without MR and only the second case with hypopituitarism. Analogous to the x-linked SOX3, duplication/deletions in ZNF673 and ZNF674 could result in short stature without MR and may be implicated in the etiology of hypopituitarism. The patient’s phenotype is probably a result of combination between the two aberrations.

Funding: Supported by the Medical University Sofia, Grant ‘Mlad issledovatel’ Nr 41-D, contract 30-D.