Connexion

GENATLAS PHENOTYPE

last update : 06-07-2011

Symbol	DEL18QD
Location	18q22.3qter
Name	chromosome 18q distal deletion
Other name(s)	18q- syndrome, monosomy 18q, de Grouchy syndrome
Corresponding gene	MBP , GALR1 , TCF4
Main clinical features	short stature, variable developmental delay/mental retardation, delayed expressive language, midface hypoplasia, downturned corners of the mouth, hearing impairment, atretic or stenotic ear canals, tapered fingers and proximally placed thumbs, foot deformities dysmyelinisation of the brain, poor coordination, frequent infections hemizygosity for TCF4 confers a significant impact primarily with regard to cognitive and motor development, resulting in a very different prognosis for individuals hemizygous for TCF4 when compared to individuals hemizygous for other regions of distal 18q. PMID: 21671075
Genetic determination	chromosomal
Prevalence	estimated frequency : 1/40 000 births
Function/system disorder	multisystem/generalized
	mental retardation
Type	MCA/MR

Gene product

Name

contiguous gene syndrome with numerous genes implicated.

Mechanism(s)

Chromosome rearrangement	Effect	Comments

deletion	haploinsufficiency	visible deletion of variable size, including the MBP gene in most cases, most breakpoints map in q21.3
translocation		recurrent cryptic unbalanced t(4;18)resulting in 18q-/4q+ imbalances and a specific phenotype

Remark(s)

evaluation of possible growth hormone deficiency is recommanded; GH replacement therapy may, in addition to increased growth, improve non-verbal IQ in most patients.

Genotype/Phenotype correlations

TCF4 (+/+) individuals were only moderately developmentally delayed while TCF4 (+/-) individuals failed to reach developmental milestones beyond those typically acquired by 12 months of age; critical regions for microcephaly (18q21.33), short stature (18q12.1-q12.3, 18q21.1-q21.33, and 18q22.3-q23), white matter disorders and delayed myelination (18q22.3-q23), growth hormone stimulation response failure (18q22.3-q23), and CAA (18q22.3). Additionally, the overall level of MR appeared to be mild in patients with deletions distal to 18q21.33 and severe in patients with deletions proximal to 18q21.31. The critical region for the typical 18q-phenotype is a region of 4.3 Mb located within 18q22.3-q23. A recessive locus for recessive BWS-like macroglossia syndrome may be located at 18q23.