Chromosome 13q14 Deletion Syndrome

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

Description

The chromosome 13q14 deletion syndrome is characterized by retinoblastoma (180200), variable degrees of mental impairment, and characteristic facial features, including high forehead, prominent philtrum, and anteverted earlobes (summary by Caselli et al., 2007).

Clinical Features

Motegi et al. (1983) suggested that patients with retinoblastoma due to an interstitial deletion of chromosome 13q have a characteristic appearance of the midface: prominent eyebrows, broad nasal bridge, bulbous tip of the nose, large mouth with thin upper lip, and long philtrum.

Fukushima et al. (1987) described a mother and son with retinoblastoma due to deletion of 13q14. They both had peculiar facies with high forehead, low and broad nasal root, short and bulbous nose, and open mouth with thin upper lip, as well as prominent earlobes. The son had enucleation of the right eye at age 13 months and no evidence of involvement of the left eye at 21 months. The mother had enucleation of the right eye at age 6 months and prophylactic x-ray therapy to the left eye. In the mother and son with retinoblastoma due to deletion of 13q14 described by Fukushima et al. (1987), the esterase D (ESD; 133280) activity of red blood cells was about 50% of normal and the esterase D haplotype was 1-0 in the mother and 2-0 in the son.

Baud et al. (1999) reported 22 patients with cytogenetically detectable rearrangements of chromosome 13q14. All had retinoblastoma, and most had specific dysmorphic facial features, including anteverted ear lobes (90%), a high and broad forehead (85%), and a prominent philtrum (65%) and short nose (55%). The phenotype was associated with severe mental retardation and/or motor impairment, such as axial hypotonia and diplegia, by age 2 years in 11 (69%) of 16 patients. The severity of mental retardation correlated with deletions that spanned chromosome 13q14-q21. Sixteen cytogenetic changes were de novo deletions, 2 were de novo translocations, and 4 were interstitial deletions due to parental insertions.

Laquis et al. (2002) reported a 9-month-old girl with an X;13 chromosomal translocation with a break point at 13q12.1 and dysmorphic facial features characteristic of 13q syndrome: large anterior fontanel, broad high forehead, hypertelorism, thin lips, anteverted ear lobes, and long philtrum. She had leukocoria in her right eye; clinical examination revealed retinoblastoma.

Caselli et al. (2007) reported 2 unrelated patients with de novo deletions of chromosome 13q14-q21 associated with retinoblastoma, characteristic facial features, and mental retardation. Brain MRI of both patients showed hypoplasia of the corpus callosum. Other features included dolichocephaly and toe crowding in 1 patient, and poor growth and short fifth toes in the other.

Deletion of Chromosome 13q14-q32

Schocket et al. (2003) reported the clinical features of a male infant with a chromosomal deletion of 13q14-q32. Physical examination revealed multiple cardiac anomalies, including a ventriculoseptal defect, supravalvular aortic narrowing, and patent foramen ovale, as well as growth deficiency, fifth finger clinodactyly, overriding second toe bilaterally, umbilical and inguinal hernias, bilateral hydronephrosis, micropenis with undescended testes, low-set ears and a hearing deficit, micrognathia, and a high palate. Bilateral hip dislocation, simian creases, and a right accessory nipple were also noted. MRI of the brain detected a partial absence of the corpus callosum, agenesis of the septum pellucidum, asymmetric thalami, and holoprosencephaly. Ophthalmologic examination showed bilateral microphthalmia and bilateral iris and chorioretinal colobomas. Although not present at birth, bilateral retinoblastoma developed at 6 months of age. Schocket et al. (2003) reviewed charts of 1,265 retinoblastoma patients; only 0.3% of cases occurred in microphthalmic eyes.

Lansink et al. (2005) reported a second patient with a chromosomal deletion encompassing the 13q13-q32 region with unilateral ocular findings of uveal coloboma combined with retinoblastoma. The other eye remained normal through 4 years of follow-up. They noted that both their patient and the patient described by Schocket et al. (2003) had a hearing deficit. Lansink et al. (2005) underscored the importance of careful examination to distinguish fibrovascular tissue within a coloboma from a retinoblastoma. In reply, Schocket et al. (2005) stated that hearing loss was not a typical manifestation of the 13q deletion syndrome and might result from the auditory pigmentary disorder Waardenburg-Shah syndrome (277580), which can be caused by mutation in the endothelin-B receptor gene (131244) on 13q22. Schocket et al. (2005) noted that unilateral findings may result from a contiguous gene deletion syndrome.

Cytogenetics

Caselli et al. (2007) used array comparative genomic hybridization to analyze the deletion breakpoints in 2 unrelated patients with chromosome 13q14-q21 deletion. They identified a 19-Mb deletion (chr13:40.40-59.29) and a 36-Mb deletion (ch13:43.24-79.27), respectively, with an overlapping 16-Mb minimal critical region for mental retardation and dysmorphic features that includes 39 known genes. Comparison with a patient with isolated retinoblastoma who inherited a 1.7-Mb deletion from her affected mother allowed the exclusion of a central region including 9 genes. Thus, 2 distinct critical regions were identified: a centromeric 4-Mb region and a telomeric 10-Mb region. Candidate genes for the neurologic phenotype in these 2 regions included NUFIP1 (604354), HTR2A (182135), and PCDH8 (603580) at chromosome 13q14, and PCDH17 (611760) at chromosome 13q21. Caselli et al. (2007) noted that all previous reports of the 13q deletion syndrome had used cytogenetic analysis.