del(1)(p36.3)

Epidemiology and Etiology:

· 1:5000 births

· ~0.5% of mental retardation with normal karyotype

· Similar frequency to del(22)(q11) syndrome

· Most common terminal deletion syndrome

· de novo (almost all)

· maternal = paternal

· 2/3 are simple terminal deletions

· 1/3 are complex

· Deletions with interrupted inverted duplications

· Large duplications and triplications with small terminal deletions

· More than one interstitial deletion on a single chromosome with normal intervening sequence

Common sites:

·

Gross features:

· Growth retardation (pre- or post-natal)

· Microcephaly

· brachycephaly

· Dysmorphic facies (variable)

· Deep-set eyes

· Flat nasal bridge

· Asymmetric ears

· Pointed chin

· Straight eyebrows

· Cardiac defects (40%)

· Dilated cardiomyopathy

· Cleft lip/palate (20-40%)

· Perisylvian polymicrogyria (characteristic)

· Hypotonia (100%)

Histologic features:

·

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

· Widely variable breakpoints (1.5 Mb to > 10 Mb)

· 40% are 3-5 Mb terminal deletions (1p36.13 to 1p36.33)

· Some are interstitial (7%)

· SKI (2 Mb from pter)

· Haploinsufficiency may cause cleft lip / palate (mouse studies)

· KCNAB2

· Haploinsufficiency may cause the seizures

· MMP23

· Haploinsufficiency may cause wide fontanelles

· Duplication may cause craniosynostosis

Other features:

· Severe mental retardation usually

· Less marked with smaller deletions

· Seizures (72%)

· Mild sensorineural hearing loss very common

References:

· Gardner & Sutherland 2005

· DECIPHER v4.4 (accessed 2010)