Koolen-de Vries syndrome (KDVS)

¿Que es Koolen-de Vries syndrome (KDVS)?

Koolen-de Vries síndrome es una condición genética poco común que se cree que ocurre en 1 en cada 55,000 personas. Es una condición descubierta recientemente y se identificó por primera vez en 2006.

Rasgos característicos del síndrome incluyen discapacidad intelectual leve-moderada con retraso en el desarrollo. El tono muscular bajo en la infancia también es un factor definitorio síntoma del síndrome.

Individuos con el síndrome a menudo se describen como personas con una personalidad alegre y sociable.

Síndrome Sinónimos:
Eliminación del cromosoma 17 q21. 31 Síndrome; Microdeleción 17 q21. 31 Síndrome

¿Qué causan los cambios genéticos Koolen-de Vries syndrome (KDVS)?

El síndrome es causado por una microdeleción de una pequeña parte del cromosoma 17 o por una mutación del gen KANSL1.

Las deleciones o mutaciones que causan el síndrome son aleatorias y la mayoría de los individuos son los primeros en su familia con el síndrome.

La herencia de microdeleciones ocurre cuando hay una deleción de varios genes en un cromosoma. El cromosoma específico en el que ocurren las deleciones determinará el síndrome que causan.

En algunos casos, un síndrome genético puede ser el resultado de una mutación de novo y el primer caso en una familia. En este caso, se trata de una nueva mutación genética que se produce durante el proceso reproductivo.

¿Cuales son los principales síntomas de Koolen-de Vries syndrome (KDVS)?

Las características faciales y físicas incluyen una nariz en forma de pera, cara alargada, frente ancha, párpados caídos y orejas muy prominentes.

Otras condiciones de salud pueden incluir epilepsia, que se estima que es una de las principales síntoma en el 50% de las personas diagnosticadas con síndrome.

También se reconocen defectos cardíacos, enfermedad renal y anomalías óseas. síntomas en algunos individuos afectados.

Posibles rasgos / características clínicas:
Puente nasal ancho, Catarata, Nariz bulbosa, Morfología anormal del tabique cardíaco, Morfología anormal de la válvula aórtica, Dilatación aórtica, Aracnodactilia, Defecto del tabique auricular, Aplasia / hipoplasia del cuerpo calloso, Válvula aórtica bicúspide, Blefarofimosis, Paladar hendido, Hipoplopigmentación del cabello, Subdesarrollo del cabello ala nasal, hipotonía generalizada, deterioro cognitivo, retraso del desarrollo global, ictiosis, hipotrofia de los músculos pequeños de la mano, retraso en el desarrollo del habla y el lenguaje, hipotiroidismo, hipotelorismo, frente ancha, puente nasal prominente, displasia de cadera, hidronefrosis, paladar alto, frente alta, Paladar alto y estrecho, Habla nasal, Hipermetropía, Cifosis, Estatura baja, Escoliosis, Espondilolistesis, Fusión vertebral, Fisura palpebral inclinada hacia arriba, Estrabismo, Orejas antevertidas, Barbilla ancha, Ptosis, Microcefalia, Número reducido de dientes, Cresta metópica prominente, Distancia intermamilar amplia , Estenosis pilórica, Expresividad variable, Esporádica, Defecto del tabique ventricular, Estenosis pulmonar osis, gene contiguo sy

¿Cómo se hace la prueba a alguien? Koolen-de Vries syndrome (KDVS)?

La prueba inicial para el síndrome de Koolen-de Vries puede comenzar con la detección del análisis facial, a través de la plataforma de telegenética FDNA Telehealth, que puede identificar los marcadores clave del síndrome y describir la necesidad de más pruebas. Seguirá una consulta con un asesor genético y luego con un genetista. 

Con base en esta consulta clínica con un genetista, se compartirán las diferentes opciones para las pruebas genéticas y se buscará el consentimiento para realizar más pruebas. ed.

Información médica sobre Koolen-de Vries síndrome

Koolen-De Vries syndrome is characterized by intellectual disability, hypotonia, a friendly demeanor, and highly distinctive facial features, including a broad forehead, long face, upslanting palpebral fissures, epicanthal folds, and tubular nose with bulbous nasal tip. More variable features include cardiac or genitourinary anomalies and seizures. The syndrome is caused by mutations in the KANSL1 gene and deletions in the chromosome 17q21.31 region (Zollino et al., 2012, Koolen et al., 2012).

Varela et al., (2006) reported a patient with many features of Angelman syndrome, who had normal standard chromosome results but a de novo 1-Mb microdeletion at 17q21.31 using array CGH. Clinically, her developmental delay was somewhat less expressed than in classical Angelman syndrome. She did not have ataxia, and she had an ASD and VSD. She developed a scoliosis at an early age.

Three patients were reported by Koolen et al., (2006). Intellectual disability was moderate. All had severe hypotonia, which led to severe motor retardation. They had long hypotonic facies, with ptosis, blepharophimosis, large low-set ears, pear-shaped noses, a long columella and hypoplastic alae nasi. The chin was broad, and all had cheerful personalities.

An excellent report of 22 patients (Koolen et al., 2008) gives a definitive picture of the dysmorphic features. The children are delayed, hypotonic, have long faces with a tubular or pear-shaped nose with bulbous tip, and the behavior is friendly.

Eleven patients were reported by Tan et al., (2009). Aortic root dilatation, recurrent joint dislocations, persistent fetal finger pads, hip dysplasia and conductive hearing loss were additional features.

A further four patients were reported by Wright et al., (2011). Patients had skin hyperpigmentation, numerous nevi and coarse facial features. Wright et al., (2011) suggest this microdeletion should be in the differential diagnosis of CFC (see elsewhere). The patient reported by Digilio et al., (2013) had a generalized increase in skin pigmentation with patchy depigmentation. Vitiligo was a feature in two patients reported by Maley et al., (2015).

Interruption of the pituitary stalk and complete growth hormone deficiency can also occur (El Chehadeh-Djebbar et al., 2011).

Two sib pairs were reported by Koonen et al., (2012). A parent had low-grade mosaicism in both.

The patient reported by Dornelles-Wawruk et al., (2013) had in addition fusion of many vertebrae and anemia. The deleted area contained MAPT, CRHR1, KANSL1, SPPL2C and STH.

A partial duplication of both thumbs, which were also broad, was reported by Barone et al., (2015).

Zollino et al., (2015) reported on genotype-phenotype correlations in 27 patients with 17q21.31 deletions and five patients with KANSL1 point mutations. Macrocephaly was detected in 24% of patients with the deletion and in 60% of those with the point mutation. Congenital heart disease was found in 35% of patients with the deletion. Koolen et al., (2015) described a cohort of 45 individuals with KdVS, of whom 33 had a 17q21.31 microdeletion and 12 carried a single-nucleotide variant in KANSL1. No genotype-phenotype correlations were apparent. The facial features were similar between the 17q21.31 deletion group and the KANSL1 mutation group. The most prominent dysmorphic features included a long face, upslanting palpebral fissures, narrow/short palpebral fissures, ptosis, epicanthal folds, tubular- or pear-shaped nose with bulbous nasal tip, everted lower lip, large prominent ears, and a high and narrow palate. Hypermetropia was present in 38%, and strabismus was noted in 41%. Hearing impairment was detected in 25% of cases and was most frequently conductive.
Ectodermal abnormalities were present in 67% of cases (multiple nevi, depigmentosa, hyperkeratosis, eczema, keratosis pilaris, café-au-lait maculae, ichthyosis vulgaris, acne vulgaris, piezogenic papules, and hemangiomas). Dental problems included enamel hypoplasia, caries, absence of secondary elements, and small, widely spaced or conical teeth. Musculoskeletal anomalies were present in 77% of cases. Intrauterine growth retardation was recorded in 26% and postnatal growth retardation in 35% of the cases. Neonatal hypotonia was reported in 86% of all cases. It frequently resulted in feeding difficulties and nasogastric tube feeding in the neonatal period. Congenital heart anomalies were present in 39% of individuals. Renal and urogenital anomalies were present in 45%.
All individuals had developmental delay/intellectual disability (mild in 42%, moderate in 37% and severe in 22%). Expressive language development was particularly affected, compared with receptive language or motor skills. Eighty-nine percent of the individuals were described as sociable and had an amiable affect. Behavioral problems were observed in 57% of cases. Seizures were present in 49% of all cases and were well-controlled with antiepileptic medications. Structural anomalies of the central nervous system were present in 53% (corpus callosum hypoplasia/aplasia, enlarged ventricles, hydrocephalus, heterotopias, communicating hydrocephalus, periventricular white matter abnormalities, and partial pituitary stalk interruption syndrome).

Ciaccio et al., (2016) described an adult patient with a 546-kb deletion in 17q21.31. The patient had typical facial appearance with long face, inverse epicanthal folds, low-set ears with hypoplastic auricular lobe, tubular nose, and microretrognathia. Additional features included scoliosis with gibbus deformity, cubitus valgus, pes planus, bilateral arachno-clinodactyly of the toes, hallux valgus, pachydermodactyly, cutaneous xerosis of pretibial region and atrophic scars.
The authors reviewed the literature on adult patients with Koolen de Vries syndrome. All the individuals presented with global developmental delay. Good language skills were reached around the 4th year of life. Cognitive impairment varied from mild to severe. Strabismus was present in 5/10, hearing impairment in 4/10, scoliosis in 8/10, joint hypermobility in 6/10, and positional feet deformity in 6/10. Epilepsy was present in up to 50% of patients. MRI abnormalities included periventricular and perivascular matter enlargement, corpus callosum, hippocampal dysplasia, and thin pituitary stalk. Congenital heart defects included pulmonary stenosis, septal defects, bicuspid aortic valve and patent ductus arteriosus. Urological abnormalities were present in up to 82% patients; joint hypermobility has been described in 73%.

Keen et al., (2017) described a 10-year-eight-month-old female with Koolen-de Vries syndrome and a frameshift heterozygous mutation in the KANSL1 gene. Clinical characteristics included hypotonia, esotropia, hip dysplasia and multiple ear infections. The intelligence was low-average with intact verbal intelligence; she had perceptual deficits, developmental dyspraxia, and severe speech disorder. Brain MRI showed mild dilatation of the ventricles, mega cisterna magna, and small pineal cyst without mass effect. Dysmorphic features included midface hypoplasia, hypertelorism, sparse eyebrows, upward slanting palpebral fissures, tubular or pear-shaped nose with a bulbous nasal tip, long and prominent philtrum, everted lower lip, abnormal hair color and texture, anterior open bite with malocclusion, and small and widely spaced teeth.

* This information is courtesy of the L M D.
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