Chromosome 1p35 Deletion Syndrome

A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome on chromosome 1p35.

Clinical Features

Wilson et al. (2015) reported 2 unrelated girls with a developmental disorder associated with overlapping de novo heterozygous deletions of chromosome 1p35. Both girls had intrauterine growth retardation, hypotonia, short stature, hypermetropia, and variable hearing impairment. Dysmorphic features were strikingly similar, including long myopathic facies, prominent forehead, neat eyebrows, almond-shaped palpebral fissures, small mouth with thin upper lip, abnormal ears, and high palate. Both had delayed motor development with gross and fine motor coordination difficulties and cognitive impairment; one girl had dysarthria and the other was nonverbal at age 7.5 years. One patient had a 2.05-Mb deletion and the other had a 5.32-Mb deletion, with a 1.03-Mb overlap containing 23 genes.

Gennarino et al. (2018) reported 9 patients with a developmental disorder associated with de novo heterozygous deletion of chromosome 1p35; 1 of the patients had previously been reported by Wilson et al. (2015). All had developmental delay, usually with language delay and intellectual disability. Six patients had ataxia, 4 had short stature, and 3 had seizures. Additional more variable features included hypotonia, motor delay, hyperactivity, attention deficit, and nonspecific dysmorphic facial features. Two patients had microcephaly. The deletions ranged from 0.3 to 5.6 Mb, and the minimal region of overlap included only the PUM1 gene. The deletions were proven to be de novo in 3 cases.