The 18q-syndrome is characterized by a deletion that involves the distal section of 18q and typically extends to the tip of the long arm. The breakpoint involved varies greatly and the presence or absence of specific clinical features may depend on the size and position of the deleted region . The increasing use of molecular techniques such as array-CGH enables more accurate definition of the breakpoints. This, in turn, enables researchers to study which parts of the chromosome correlate with the different clinical features of the condition .
It is generally characterized by mental retardation, development delay, short stature, hearing loss, white matter abnormalities of the brain, neurologic abnormalities such hypoplasia, hands and feet malformation and ocular anomalies [5, 6]. The facial dysmorphism may include brachycephaly, midface hypoplasia, everted lower lip, narrow upper lip with absent philtrum, downturned corners of the mouth, depressed and wide nasal bridge, small teeth, deep-set eyes with downslanting palpebral fissures, epicanthus, strabismus, prominent anthelix and antitragus, and very narrow external ear canal . The associated anomalies include vertebral anomalies, genitourinary changes, congenital heart defects, cleft lip and palate .
It is thought that the decreased growth may be due to a growth hormone deficiency. This region contains the genes myelin basic protein (MBP) and the galanin receptor which are both candidates for the growth hormone insufficiency. The galanin receptor is involved in growth hormone response and is therefore a good candidate for the growth hormone insufficiency [9, 11]. Interestingly, this region is almost identical to the region that has been identified to be responsible for the myelination problems. Thus, the gene or genes responsible for these two features are either the same gene or two tightly-linked genes. Up until now, all people who have been shown to have dysmyelination also have a growth hormone deficiency, so it has not yet been possible to uncouple these two features . The common finding of narrow ear canals in 18q- has been linked, by three studies, to the loss of part of the region 18q22.3 [9, 12].
A critical region for the microcephaly (small head) that is often present in 18q- has been shown to be located to band 18q21.33 [8, 9].
Chromosome 1p duplications have been reported rarely and his contribute to patient’s phenotype it’s difficult to estimate. A review of the literature suggests that there is not possible to establish a syndrome. The most consistent manifestations are low birth weight, grow retardation, craniofacial and hand anomalies, and congenital heart disease. Most males had abnormal genitalia, whereas females had normal genitalia . Apart from not specific features such as microcephaly, growth retardation, and developmental delay, the most striking feature reported in previous studies is metopic, sagittal and coronal synostosis .
Such opposing phenotypes, cranial synostosis in dup(1)(p36)and large late closing anterior fontanels in del(1)(p36) is probably corraleted to a gene that regulates suture closure at chromosome 1p36 . Chromosome 1p36 rearrangements have been associated also with various neoplasms such as neuroblastoma suggesting that 1p36 region contain a tumor-suppressor gene involved in malignancy .
The coexistence of two chromosomal rearrangements complicates the clinical picture and creates a chimeric disorder marked by characteristics of both chromosomal anomalies.
The patient reported presents not specific characteristics like growth and psychomotor retardation and also feet malformation and microcephaly found in both anomalies.
The most clinical features as hypotonia, midface hypoplasia, micrognatia, wide philtrum, small teeth, deep-set eyes with downslanting palpebral fissures, umbilical hernia and RVU are related to 18q deletion syndrome.
The patient also present hyperthelorisme, depressed and wide nasal bridge probably related to 1p36.3 duplication.
Patient’s clinical phenotype isn’t completely superimposable to the one present in 18q syndrome, for example, hearing abnormality, one of the most consistent features with 66 per cent of children affected, it is absent in this patient. This is probably consequent to the great breakpoint variability and to the simultaneous presence of 1p duplication.
Concerning VUR for which the patient referred to our clinic, most researchers now acknowledge that VUR is genetically heterogeneous .
The initial evidence suggesting a genetic origin of primary VUR came from twin studies, showing an 80%–100% concordance for VUR in monozygotic twins vs. a 35-50% concordance in dizygotic twins .
Studies of humans with chromosomal abnormalities suggest for not syndromic primary VUR candidate loci or genes on chromosomes 6p, 10q26, 19q13 and 13q33-34 .
M.L. Conte et al showed best evidence of linkage with VUR on chromosome 3 p12.3-3q24 and on chromosome 1p36.32-1p34.3.
None of 13 reported patients affected by chromosome 1p36 terminal duplications evidenced the presence of VUR.
No part of the chromosome 18 has yet been identified related to VUR despite is reported approximately in 15% of patient affected by syndrome 18q.