del(15)(q24q24)

Epidemiology and Etiology:

· Note: this microdeletion is different from the previously FISH-identified 15q24 deletions including the PML locus

· 0.3% of idiopathic MR and congenital anomalies

· de novo in all 3 available

· maternal in all 3 available (but no known imprinted genes here)

· NAHR most likely mechanism

Common sites:

·

Gross features:

· Low birthweight, poor postnatal growth

· Craniofacial dysmorphism

· Asymmetry

· Happy facial expression

· High anterior hairline

· Widening of medial eyebrows

· Hypertelorism

· Downslanting palpebral fissures

· Broad nasal base

· Flaring of alae nasi

· Abnormal ears

· Long philtrum with a full lower lip

· Nonspecific eye abnormalities

· Microphthalmia

· Strabismus

· nystagmus

· Minor digital anomalies

· Proximal thumbs

· Mild brachydactyly

· Mild cutaneous syndactyly (2-3 and 3-4 fingers, 2-3 toes)

· Camptodactyly

· Long slender fingers

· Joint laxity

· Hypospadias

· Bowel atresia (2 of 4)

·

Histologic features:

·

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

· Telomeric to PML locus

· 1.7 to 3.9 Mb deletions

· 1.7 Mb minimally deleted region (72.15 to 73.85 Mb, NCBI 36.1)

· 32 known genes

· P450scc enzyme may contribute to genital abnormalities

· Linked to congenital lipoid adrenal hyperplasia

· Proximal breakpoint at seg dup BP1 (3 of 4)

· Distal breakpoint at homologous seg dups BP2 (1 patient) and BP3 (2 patients)

Other features:

· DD (mild to moderate)

· GH deficiency with hypogonadotrophic hypogonadism and delayed puberty (2 of 4)

· ADHD / autistiform traits (1 patient)

· Seizures with brain malformations (CC, pituitary) (1 patient)

References:

· Slavotinek AM. Novel microdeletion syndromes detected by chromosome microarrays. Hum. Genet. 2008;124(1):1-17.