Abstract
BackgroundThe deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism. Similarly the phenotype of individuals with terminal deletions of distal chromosome 3p (3p deletion syndrome) varies from mild to severe intellectual deficit, micro- and trigonocephaly, and a distinct facial appearance.Methods and resultsWe investigated a large Indian five-generation pedigree with ten affected family members in which chromosomal microarray and fluorescence in situ hybridization analyses disclosed a complex rearrangement involving chromosomal subregions 4p16.1 and 3p26.3 resulting in a 4p16.1 deletion and 3p26.3 microduplication in three individuals, and a 4p16.1 duplication and 3p26.3 microdeletion in seven individuals. A typical clinical presentation of WHS was observed in all three cases with 4p16.1 deletion and 3p26.3 microduplication. Individuals with a 4p16.1 duplication and 3p26.3 microdeletion demonstrated a range of clinical features including typical 3p microdeletion or 4p partial trisomy syndrome to more severe neurodevelopmental delay with distinct dysmorphic features.ConclusionWe present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome amongst affected individuals.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-015-0251-5) contains supplementary material, which is available to authorized users.
Highlights
The deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism
We present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn, 3p deletion, and 4p duplication syndrome amongst affected individuals
Microscopically visible rearrangements of chromosome 4p16 may result in two separate syndromes: Wolf– Hirschhorn syndrome (WHS) and partial trisomy 4p syndrome
Summary
Study approval The present studies were reviewed and approved by the senior investigators from Banaras Hindu University, Varanasi, UP and Medical College, Trivandrum, Kerala and Royal Devon & Exeter NHS Foundation Trust. At the age of 2 he had not developed speech and walking, could sit with support and independently roll from back to front He developed epilepsy with generalized tonic-clonic seizures at 12 months, which is currently under control on phenytoin. Individual IV: was born pre-term (birth weight 1.2 kg) to consanguineous parents He had severe developmental delay with no speech and walked with support at age 3. He has a history of surgically treated cleft lip and complex partial seizures On neurological examination he had gaze evoked nystagmus, limb ataxia, gait ataxia; exaggerated knee and ankle jerks and up-going plantar reflexes. III: was the eldest affected child of the third generation She had no speech or walk until age 2 and has medically resistant secondarily generalized tonic-clonic seizures. For FISH, Kreatech probes D4S33060 and D3S4558 were used to define either balanced or unbalanced t(3p;4p) translocations in three individuals, case V:2, IV: and III: on whom samples were available for study (Additional file 1: Figure S3)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
