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Koolen-De Vries syndrome
Monosomy 17q21.31 (17q21.31 microdeletion syndrome) is a chromosomal anomaly characterized by developmental delay, childhood hypotonia, facial dysmorphism, and a friendly/amiable behavior.
The prevalence of the syndrome is estimated at around 1/16,000 and the deletion occurs with equal frequency in males and females.
Hypotonia (with poor sucking and slow feeding) is evident at birth. The facial dysmorphism is characterized by a high/broad forehead, long face, upward slanting palpebral fissures, epicanthic folds, an abnormally shaped nose (either 'tubular'' or 'pear''-shaped), a bulbous nasal tip, large prominent ears and an everted lower lip. Abnormal hair pigmentation and texture is also frequent. The facial phenotype may evolve with age, with coarsening and elongation of the face. Short stature, pectus excavatum, spine anomalies, dislocation of the hip(s), long slender fingers and slender lower limbs, and positional deformities of the hands/feet have also been reported. In all patients, global psychomotor developmental delay is noted from an early age, but severity varies from mild to severe. A history of epilepsy is noted in 50% of all cases and other neurological problems may also be present. Other features include heart defects (atrial and ventricular septal defects), kidney and urologic anomalies, and cryptorchidism.
The recurrent 17q21.31 deletion is between 500-650kb in size, encompassing at least six genes: C17orf69, CRHR1, IMP5, MAPT, STH and KIAA1267. A 900-kb inversion polymorphism (H2 lineage) encompasses the deletion. So far, in all cases tested, at least one of the parents is a carrier of this common inversion, suggesting that the inversion is a necessary factor for the deletion to occur.
The majority of patients reported so far were identified through screening of individuals with intellectual deficit for genomic copy number changes. The 17q21.31 microdeletion can be detected using a range of molecular techniques including array based comparative genomic hybridization (array CGH) and fluorescence in situ hybridization (FISH).
Differential diagnoses include Prader-Willi syndrome in the neonatal period and velocardiofacial syndrome in older patients (see these terms).
Genetic counseling should be proposed to parents of affected individuals, but the 17q21.31 microdeletion is sporadic and all deletions detected so far occurred de novo.
Management and treatment
Individuals with a 17q21.31 microdeletion should have routine examinations by the primary care physician and pediatrician. Cardiac investigations, and kidney and urologic evaluations are warranted. Referral to other specialists is indicated if neurological or other systemic problems are suspected.
Life-threatening malformations have not been reported in individuals with monosomy 17q21.31, however, long-term studies are required to determine the prognosis in adult patients. Autonomy is likely to be limited and affected individuals will probably require life-long support from caregivers.