Growth pattern in Kabuki syndrome with a <i>KMT2D</i> mutation

Schött, D; Blok, Marinus J.; Gerver, Willem‐Jan M.; Devriendt, Koenraad; Zimmermann, Luc J. I.; Stumpel, Constance T. R. M.

doi:10.1002/ajmg.a.37930

Cited by 30 publications

(31 citation statements)

References 27 publications

(31 reference statements)

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“…In this series, 39% of KS1 individuals showed postnatal growth retardation, with H < −2 SD (35 of 89:17 of 51 males and 18 of 38 females) (Table S7). Our data are consistent with the literature (−2 SD in 35–71% individuals) (Armstrong et al, ; Matsumoto & Niikawa, ; Schott et al, ; Schrander‐Stumpel et al, ).…”

Section: Discussionsupporting

confidence: 93%

Growth charts in Kabuki syndrome 1

Ruault¹,

Corsini²,

Akouete³

et al. 2019

American J of Med Genetics Pt A

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Kabuki syndrome (KS, KS1: OMIM 147920 and KS2: OMIM 300867) is caused by pathogenic variations in KMT2D or KDM6A. KS is characterized by multiple congenital anomalies and neurodevelopmental disorders. Growth restriction is frequently reported. Here we aimed to create specific growth charts for individuals with KS1, identify parameters used for size prognosis and investigate the impact of growth hormone therapy on adult height. Growth parameters and parental size were obtained for 95 KS1 individuals (41 females). Growth charts for height, weight, body mass index (BMI) and occipitofrontal circumference were generated in standard deviation values for the first time in KS1. Statural growth of KS1 individuals was compared to parental target size. According to the charts, height, weight, BMI, and occipitofrontal circumference were lower for KS1 individuals than the normative French population. For males and females, the mean growth of KS1 individuals was −2 and −1.8 SD of their parental target size, respectively. Growth hormone therapy did not increase size beyond the predicted size. This study, from the largest cohort available, proposes growth charts for widespread use in the management of KS1, especially for size prognosis and screening of other diseases responsible for growth impairment beyond a calculated specific target size.

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Section: Discussionsupporting

confidence: 93%

Growth charts in Kabuki syndrome 1

Ruault¹,

Corsini²,

Akouete³

et al. 2019

American J of Med Genetics Pt A

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“…In a recent study, we confirmed this physical manifestation in the Dutch and Belgian KS population [5], where the mean adult height in men was 162 cm and that for women 147.7 cm. The cause of this growth retardation is unknown, but there are several reports of growth hormone (GH) deficiency in the literature [6-9].…”

Section: Introductionsupporting

confidence: 62%

“…We previously described the growth pattern among Dutch and Belgian KS subjects with a KMT2D mutation [5]. All of them showed a reduction in growth during childhood, but a genotype-phenotype correlation was not observed.…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone Therapy in Children with Kabuki Syndrome: 1-year Treatment Results

2017

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Background/Aims: Kabuki syndrome (KS) is a rare genetic malformation syndrome, resulting in characteristic features such as short stature. We investigate whether growth hormone (GH) treatment increases linear height and influences body proportions in KS children. Methods: In this prospective study, 18 genetically confirmed prepubertal KS children (9 females and 9 males) aged from 3.8 to 10.1 years (mean 6.8 ± 2.1 years) were treated with recombinant human GH (rhGH) for 1 year. Calculations for height, height velocity, BMI, sitting height, and subischial leg length were made. Bone age, insulin-like growth factor (IGF-I), and IGF binding protein 3 (IGFBP-3) were also measured. Results: This study showed an increase in height standard deviation score (SDS) for the whole group from –2.40 to –1.69 (p < 0.05) after 1 year of rhGH treatment. The change in height SDS within 1 year was >0.7 SDS for 10 subjects and >0.5 SDS for 3 subjects. The mean IGF-I SDS at the start of the study was –0.70 (±1.07), which increased after 12 months to 1.41 (±0.91) (p < 0.05). KS children who received rhGH at a younger age displayed significantly greater increases in height than those who started when they were older. The same was true for both gene mutation KMT2D versus KDM6A and for GH deficiency versus non-GH deficiency KS children (p < 0.05). Throughout the course of rhGH treatment, the subjects’ body proportions remained normal. Conclusions: All participants experienced catch-up growth during the year of rhGH treatment, but without an influence on body proportions.

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“…The loss of KMT2D gene function on chromosome 12 in humans has been described as responsible for Kabuki syndrome (KS), a rare autosomal dominant congenital disorder characterized by multiple anomalies involving the development and function of various organ systems . Major clinical components include typical facial dysmorphic features, postnatal growth retardation, hypotonia, skeletal abnormalities, dermatoglyphic changes and mild to moderate intellectual disability …”

Section: Introductionmentioning

confidence: 99%

“…12 Major clinical components include typical facial dysmorphic features, postnatal growth retardation, hypotonia, skeletal abnormalities, dermatoglyphic changes and mild to moderate intellectual disability. [13][14][15] This study established a strategic exome sequencing methodology to select potential causative mutations in an ENU-induced mutant with a BALB/cJ background. Then, after the identification of a single missense mutation in the Kmt2d candidate gene, we used behavioral tests to evaluate the bapa mutant and its potential as a novel mouse model to study brain-associated diseases such as KS.…”

Section: Introductionmentioning

confidence: 99%

Genetic and behavioral characterization of a Kmt2d mouse mutant, a new model for Kabuki Syndrome

Yamamoto

Souza

Antiorio

et al. 2019

Genes Brain and Behavior

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The recessive mutant mice bate palmas (bapa) ‐ claps in Portuguese arose from N‐ethyl‐N‐nitrosourea mutagenesis. A single nucleotide, T > C, change in exon 13, leading to a Thr1289Ala substitution, was identified in the lysine (K)‐specific methyltransferase 2D gene (Kmt2d) located on chromosome 15. Mutations with a loss‐of‐function in the KMT2D gene on chromosome 12 in humans are responsible for Kabuki syndrome (KS). Phenotypic characterization of the bapa mutant was performed using a behavioral test battery to evaluate the parameters related to general activity, the sensory nervous system, the psychomotor system, and the autonomous nervous system, as well as to measure motor function and spatial memory. Relative to BALB/cJ mice, the bapa mutant showed sensory and psychomotor impairments, such as hypotonia denoted by a surface righting reflex impairment and hindquarter fall, and a reduction in the auricular reflex, suggesting hearing impairment. Additionally, the enhanced general activity showed by the increased rearing and grooming frequency, distance traveled and average speed possibly presupposes the presence of hyperactivity of bapa mice compared with the control group. A slight motor coordination dysfunction was showed in bapa mice, which had a longer crossing time on the balance beam compared with BALB/cJ controls. Male bapa mice also showed spatial gait pattern changes, such as a shorter stride length and shorter step length. In conclusion, the bapa mouse may be a valuable animal model to study the mechanisms involved in psychomotor and behavior impairments, such as hypotonia, fine motor coordination and hyperactivity linked to the Kmt2d mutation.

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Growth pattern in Kabuki syndrome with a KMT2D mutation

Cited by 30 publications

References 27 publications

Growth charts in Kabuki syndrome 1

Growth charts in Kabuki syndrome 1

Growth Hormone Therapy in Children with Kabuki Syndrome: 1-year Treatment Results

Genetic and behavioral characterization of a Kmt2d mouse mutant, a new model for Kabuki Syndrome

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