Chromosome 6q11-Q14 Deletion Syndrome

A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome on chromosome 6q.

Description

The cardinal features of chromosome 6q11-q14 interstitial deletions include hypotonia, short stature, skeletal/limb anomalies, umbilical hernia, and urinary tract anomalies, as well as characteristic facial features including upslanting palpebral fissures, low-set and/or dysplastic ears, and high-arched palate (summary by Wang et al., 2009).

Clinical Features

Young et al. (1985) described a 2.75-year-old Caucasian girl with feeding problems in infancy, hiatal and inguinal hernias, left exotropia, lacrimal duct atresia, and short achilles tendons. She had generalized hypotonia and was unable to sit, with obvious developmental delay. Her head circumference was in the 70th centile, and she had a dolichocephalic cranium, low temporal hairline, lateral widening of eyebrows, large ears with prehelical and lobar pits, mild enophthalmos, upslanting palpebral fissures, epicanthic folds, broad nose, long philtrum, narrow palate, and missing upper lateral incisors. She also had short hands, single palmar creases, ulnar deviation of the second fingers, and small, concave nails; her great toes were long with valgus deviation, and she had right partial 2/3 syndactyly.

Slater et al. (1988) described a 9-month-old male infant who was born with head circumference in the 3rd centile, micrognathia, high-arched palate, shallow philtrum, narrow upper vermilion border, short neck, undescended testicles, long slender fingers, long flat feet with prominent heels, and a pigmented nevus on the thigh. At 9 months of age, his height, weight, and head circumference were all below the 3rd centile, there was obvious psychomotor retardation; additional findings included horizontal palpebral fissures, hypotelorism, and a strange, laugh-like cry.

Gershoni-Baruch et al. (1996) reported a 2-year-old Arab Moslem boy who was initially seen at 8 months of age for developmental delay, postnatal growth failure, and facial anomalies that included deep-set eyes, small palpebral fissures, hypotelorism, nystagmus, blue sclerae, mongolian slant, mild synophrys, posteriorly rotated low-set ears with large pinnae, low frontal hairline, slender nose with small anteverted nostrils, flat maxillae, high-arched palate, micrognathia, short frenulum, and broad short neck. He had a single palmar crease, hyperextensible fingers and wrists, 2/3 and 4/5 skin syndactyly of fingers and 2/3 syndactyly of toes, clubfeet, hyperelastic and redundant skin, umbilical hernia, right inguinal hernia, micropenis, and left undescended testis. In addition to global developmental delay, there was generalized hypotonia.

Kumar et al. (1997) reported an 8-year-old boy with a known interstitial deletion of chromosome 6q, who at birth was noted to have mild facial asymmetry, large low-set ears with auricular pits, bifrontal narrowing of the forehead, prominent occiput with dolichocephalic skull shape, wide bulbous tip of nose, elongated philtrum, high-arched palate, bilateral single palmar creases, long tapered digits, bilateral cryptorchidism, subluxation of the hips, and hypermobility of all large joints. At 8 years of age, he exhibited significant hypotonia and psychomotor delay.

Wang et al. (2009) described 7 patients with chromosome 6q11-q14 interstitial deletions, 3 of whom were from the same large pedigree. Features consistent with previous reports included hypotonia, upslanting palpebral fissures, low-set and/or dysplastic ears, high-arched palate, single palmar creases, and umbilical hernia; however, less than 30% of these patients displayed other typical features such as epicanthic folds, hypertelorism, short nose, broad nasal tip, long philtrum, thin upper lip, strabismus, short neck, and scoliosis, which were shared by over 50% of previously reported patients.

Cytogenetics

Young et al. (1985) performed karyotype analysis in a 2.75-year-old girl with hypotonia, developmental delay, hiatal and inguinal hernias, and facial dysmorphism, and found an interstitial deletion of chromosome 6q13-q15.

In a 9-month-old male infant with failure to thrive, psychomotor delay, facial dysmorphism, and umbilical hernia, chromosome analysis by Slater et al. (1988) revealed an interstitial deletion of chromosome 6q11-q15.

In a 2-year-old Arab Moslem boy with growth retardation, developmental delay, umbilical and inguinal hernias, and facial and urogenital anomalies, Gershoni-Baruch et al. (1996) performed karyotype analysis and detected a deletion of chromosome 6q13-q15.

In an 8-year-old boy with a characteristic facial appearance and psychomotor delay, Kumar et al. (1997) demonstrated a deletion of chromosome 6q13-q14.2.

In 7 patients with chromosome 6q11-q14 interstitial deletions of various sizes, Wang et al. (2009) analyzed the breakpoints by dual-color BAC-FISH analysis and found the average deletion size to be 13.9 Mb. The minimum deleted region was between base positions 73.9 and 79.5 Mb at chromosome 6q13-q14.1 and contained the COL12A1 gene (120320). In addition, the COL9A1 (120210) and COL19A1 (120165) genes were deleted in 3 patients with deletion breakpoints that were more centromeric than the other 4 patients. SNP array analysis confirmed the deletion breakpoints in 1 of 2 half sibs inheriting a recombinant chromosome 6 containing a 6q13-q14.2 deletion from their carrier mother who had a chromosome 6 between-arm intrachromosomal insertion. The mother's male second cousin was also a carrier of the intrachromosomal insertion, and his son inherited a recombinant chromosome 6 containing a 6q13-q14.2 deletion as well.

Van Esch et al. (2010) reported 4 patients with a de novo interstitial deletion of chromosome 6q13-q14, resulting in a common 3.7-Mb minimum deleted region between base positions 72.65 and 76.31 Mb. All presented with developmental delay, mild dysmorphism similar to that seen in previously reported patients, including long philtrum, thin upper vermilion border, pointed chin, and large ear lobes, and signs of lax connective tissue. Van Esch et al. (2010) noted that the common deleted region harbored 16 genes, of which COL12A1 was a good candidate for the connective tissue pathology.