Bilateral perisylvian polymicrogyria, periventricular nodular heterotopia, and left ventricular noncompaction in a girl with 10.5–11.1 Mb terminal deletion of 1p36

Abstract

Monosomy 1p36 is a common subtelomeric microdeletion syndrome, characterized by craniofacial dysmorphisms, developmental delay, mental retardation, hypotonia, epilepsy, cardiovascular complications, and hearing impairment; deleted regions have been mapped within 10.0 Mb from the telomere in most documented cases. We report on a girl with a 10.5-11.1 Mb terminal deletion of 1p36 shown by fluorescence in situ hybridization (FISH). She had three distinct structural abnormalities: bilateral perisylvian polymicrogyria, periventricular nodular heterotopia, and left ventricular noncompaction. She died in early infancy with intractable epilepsy, progressive congestive heart failure and pulmonary hypertension. To date, this is the first case with monosomy 1p36, complicated by this combination of manifestations; she is also the first who had possibly a simple terminal deletion of 1p36 and died in early infancy. An atypically large deletion in this patient might be the basis for the development of these features and the severe clinical course.

Recurrence risks for different pregnancy outcomes and meiotic segregation analysis of spermatozoa in carriers of t(1;11)(p36.22;q12.2)

“…7,16 Our observation confirms two previous suggestions of Saito et al 37 and Nicoulaz et al 35 that 1p36 region for pure distal terminal deletions, 411 Mb is the haplolethal. Although many large 1p36 deletions~10-11 Mb in size are likely nonlethal, 39,[42][43][44] additional observations are necessary to determine if monosomy 1p36-pter sized 411 Mb is risk factor for limited survival rate.…”

“…39,[42][43][44] However, deletions over 11-16 Mb may be lethal. 36,37 As in our case, unbalanced segregants that result in double segment imbalances will impact the survival rate and is dependent on the size of the two segments and genetic content.…”

Microarray analysis of 50 patients reveals the critical chromosomal regions responsible for 1p36 deletion syndrome-related complications

“…Several case reports have suggested an association between periventricular nodular heterotopia (PVNH) and 1p36 deletion [16,[30][31][32], and the candidate region for polymicrogyria has been mapped to the distal 4.8 Mb region [33]. As the smallest deletion among the patients with abnormal neuronal migration was 3.0 Mb (Pt 8), the gene(s) responsible for this phenotype may be narrowed down to the distal 3.0 Mb region ( Fig.…”

Periventricular Heterotopia in Common Microdeletion Syndromes

“…van Kogelenberg et al It was reasonable for Neal et al [2006] and Saito et al [2008] to suggest the existence of a PH gene at 1p36 on the grounds that the deletions they described extended further towards the centromere than deletions typically observed in 1p36 deletion syndrome. Now that a patient with PH has been described with a 5-Mb telomeric 1p36 deletion, this proposition is weakened although a lowly penetrant position effect remains a formal possibility and molecular and imaging studies of further individuals with a 1p36 deletion will help clarify this issue.…”

“…Several of these descriptions have prompted speculation that novel PH loci might lie within these deleted regions, invoking haploinsufficiency for a critical gene as the proposed mechanism [Sheen et al, 2003;Ferland et al, 2006;Neal et al, 2006;GawlikKuklinska et al, 2008], a contention strengthened by the characterisation of deletions that are larger than commonly seen in the 1p36 deletion syndrome and in Williams syndromes [Ferland et al, 2006;Neal et al, 2006;Saito et al, 2008]. With the notable exceptions of anomalies noted on 5p15 [Sheen et al, 2003] and 5q11 [Cardoso et al, 2009], very few of these described chromosomal anomalies have been recurrently and consistently observed in association with PH ( table 1 ).…”