Clinical Description
Koolen-de Vries syndrome (KdVS) has a clinically recognizable phenotype that includes neonatal/childhood hypotonia, developmental delay / intellectual disability, dysmorphisms (), speech and language delays, congenital malformations, and behavioral features (Table 2). Males and females are affected equally.
Table 2.
Features of Koolen-de Vries Syndrome
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Frequency | Feature |
---|
Very common
(>75% of
individuals)
| Distinctive facial features (See Dysmorphic craniofacial features following table.) Hypotonia (neonatal/childhood) Developmental delay / intellectual disability Speech & language delay Friendly/amiable disposition
|
Common
(50%-75%)
|
|
Less common
(25%-50%)
|
|
Occasional
(10%-25%)
|
|
Infrequent
(<10%)
| Autistic behavior Craniosynostosis Sacral dimple Spondylolisthesis Dural ectasia Spina bifida Pineal cyst Cervical spinal canal stenosis Recurrent urinary tract infections Recurrent respiratory infections Recurrent otitis media Eczema Hypopigmentation of the skin / vitiligo Alopecia Café au lait spots Ichthyosis/hyperkeratosis Growth hormone deficiency Hypothyroidism Precocious puberty Primary adrenal insufficiency Melanoma Testicular neoplasm Hemangioma
|
Dysmorphic craniofacial features that may suggest KdVS:
The nose can have a high nasal bridge, a broad nasal root, long columella, and underdeveloped and/or thick alae nasi. The facial characteristics change with age. In infancy the facial gestalt is mostly characterized by hypotonia with an open mouth appearance. With increasing age there is usually elongation of the face and broadening of the chin, and the "tubular'' or "pear'' shape form of the nose may become more apparent.
Hypotonia with poor sucking and slow feeding can be evident in the neonatal period and during childhood. Feeding difficulties may require hospitalization and/or nasogastric tube feeding in some neonates. Beyond infancy and into the preschool years, many children experience problems chewing difficult, lumpy, or solid textures [Morgan et al 2018a].
Psychomotor developmental delay is noted in all individuals from an early age. The level of developmental delay varies significantly. The majority of individuals with KdVS function in the mild-to-moderate range of intellectual disability.
Communication disorder is a core feature of KdVS with a common speech and language
phenotype seen. This includes an overriding "double hit" of oral hypotonia and apraxia in infancy and preschool, associated with severely delayed speech development [
Morgan et al 2018a].
First words occur between ages 2.5 and 3.5 years on average.
Childhood apraxia of speech (CAS) is common in these preschool years, and speech development is effortful even when supported with intensive therapy.
Augmentative (e.g., sign language) or alternative (e.g., communication devices) communication may alleviate frustration for the child and promote communication development.
Overall, however, speech prognosis is positive, with CAS improving markedly around age eight to 12 years. At this time, the dysarthric element of speech is more apparent with a slow rate and monotone presentation.
Stuttering is present in a handful of cases (17%), and has been noted in adolescence only.
Receptive and expressive language abilities are typically commensurate (79%), both being severely affected relative to peers.
Children are reported as sociable with a desire to communicate; in some individuals (36%) social skill impairments appear with increasing age and increasing social demands.
Epilepsy, including generalized seizures and unilateral clonic seizures, is noted in approximately 33% of affected individuals. The epilepsy phenotypic spectrum in KdVS is broad; however, most individuals have focal seizures, with some having a phenotype resembling the self-limited focal epilepsies of childhood [Myers et al 2017].
Other common findings (see Table 2) include dental anomalies, slender long fingers, persistence of the fetal fingertip pads, hypoplasia of the hand muscles, slender lower limbs, joint hypermobility, hip dislocation, and positional deformities of the feet. In addition, multiple nevi, other pigmentary skin abnormalities, and hair abnormalities have been reported [Wright et al 2011, Zollino et al 2015, Koolen et al 2016].
Congenital heart defects mainly include septal heart defects; however, cardiac valve disease, aortic root dilatation, and pulmonary stenosis have also been described.
Renal and urologic anomalies include vesicoureteral reflux, hydronephrosis, pyelectasis, and duplex renal system. Cryptorchidism has been reported in the majority of males.
Scoliosis is the most commonly observed spine anomaly; lordosis and kyphosis have also been reported and sometimes require surgery [
Koolen et al 2008,
Tan et al 2009].
Behavior. In the vast majority of individuals, behavior is described as friendly, amiable, and cooperative, with or without frequent laughing. However, behavioral issues, including attention-deficit/hyperactivity disorder, have been reported [
Koolen et al 2008,
Tan et al 2009,
Koolen et al 2016].
Growth. Short stature is not one of the most common clinical features of the syndrome. However, El Chehadeh-Djebbar et al [2011] reported on a child with a 17q21.31 deletion, short stature (-4 SD), complete growth hormone deficiency, and gonadotropic deficiency [El Chehadeh-Djebbar et al 2011]. Brain MRI showed partial pituitary stalk interruption, expanding the phenotypic spectrum of the syndrome.
Life span. Longitudinal data are insufficient to determine life expectancy, although survival into adulthood is typical.