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Abstract #27916 Published in IGR 13-1
Pitt-Hopkins syndrome and erythropoietic protoporphyria in a patient with 18Q21 deletion diagnosed by SNP array
Tsiakas K; Grosse R; Uyanik G; Fuchs S; Santer RJournal of Inherited Metabolic Disease 2010; 33: S186
Haploinsufficiency ofTCF4 on chromosome 18q21.2 or heterozygosity for point mutations within this gene encoding transcription factor 4 were recently identified as the underlying cause of Pitt-Hopkins syndrome (PTHS), an autism spectrum disorder with dysmorphic features and breathing abnormalities. Erythropoietic protoporphyria (EPP) typically follows an autosomal (pseudo)dominant trait; it is caused by mutations of the ferrochelatase gene (FECH) on chromosome 18q21.3. Clinical expression of the disease with photosensitivity and liver complications results from coinheritance of the common hypomorphic allele IVS3 48C trans to a deleterious FECH mutation. We present a patient with PTHS and EPP as a contiguous gene syndrome caused by a large deletion in 18q21.2-q21.32. Case Report: Clinical characteristics of the 13-years-old female patient, born to consanguineous Turkish parents, were dysmorphic features, severe muscular hypotonia, apnea episodes, hyperventilation, severe psychomotor and mental retardation, dystonia, lack of speech development, lack of walking ability, short stature and glaucoma. Slight photosensitivity was noticed after direct sun exposition; no hepatic manifestations till now. EPP was confirmed biochemically by increased erythrocyte and fecal proto- phorphyrin. SNP array revealed a 5.4 Mbp deletion in 18q21.2-q21.32 affecting both the TCF4 and FECH locus. The second allele harbored the low expression FECH polymorphism IVS3-48C. Discussion: Coexistence of PTHS und EPP has only once been published in the literature in a patient with an 18q21 deletion long ago before the genetic background of these two entities was fully understood. To our knowledge, this is the first patient with PTHS and EPP, who is completely characterized on the genetic level.
K. Tsiakas. Dep. Ped., Univ. Med. Cen, Hamburg-Eppendorf, Hamburg, Germany.
Classification:
9.4.15 Glaucoma in relation to systemic disease (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)