Identification of proximal 1p36 deletions using array-CGH: a possible new syndrome

Area of Science:

• Genetics
• Human Genetics
• Clinical Genetics

Background:

• Monosomy 1p36 is the most common terminal deletion syndrome, characterized by specific genetic deletions and distinct clinical features.
• Classical monosomy 1p36 deletions typically involve 1pter-1p36.23 and result in intellectual disability, developmental delay, and characteristic facial dysmorphies.

Purpose of the Study:

• To investigate and characterize a cohort of patients with atypical proximal interstitial deletions in the 1p36.23-1p36.11 region.
• To differentiate the clinical phenotype associated with these proximal deletions from the classical distal 1p36 deletion syndrome.

Main Methods:

• Utilized array-comparative genomic hybridization (array-CGH) to identify and analyze deletions in five patients.
• Correlated molecular findings with detailed clinical data, including growth, development, neurological, cardiovascular, and dysmorphic features.

Main Results:

• Identified five patients with proximal interstitial deletions in 1p36.23-1p36.11, ranging from 2.97 Mb to 14.69 Mb.
• Observed a distinct clinical presentation including growth deficiency, feeding difficulties, seizures, developmental delay, cardiovascular malformations, microcephaly, limb anomalies, and specific dysmorphic features like frontal bossing and hypertelorism.
• Noted hirsutism in most affected children, a feature not typically associated with classical monosomy 1p36.

Conclusions:

• The proximal interstitial deletions in 1p36.23-1p36.11 represent a distinct chromosomal abnormality.
• This distinct deletion syndrome presents a unique set of clinical characteristics that differentiate it from the classical distal 1p36 deletion syndrome.