Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jul 23:2:101873.
doi: 10.1016/j.gimo.2024.101873. eCollection 2024.

ARID1B-related disorder in 87 adults: Natural history and self-sustainability

P J van der Sluijs  1 , M Gösgens  1 , A J M Dingemans  2 , P Striano  3   4 , A Riva  4   5 , C Mignot  6 , A Faudet  7 , G Vasileiou  8   9 , M Walther  8 , S A Schrier Vergano  10   11 , M Alders  12 , F S Alkuraya  13   14 , I Alorainy  15 , H S Alsaif  13   16 , B Anderlid  17 , I Bache  18 , I van Beek  12 , M Blanluet  19 , B W van Bon  20 , T Brunet  21   22 , H Brunner  2 , M L Carriero  23 , P Charles  6 , N Chatron  24   25 , E Coccia  26 , C Dubourg  27   28 , R K Earl  29 , E E Eichler  30   31 , L Faivre  32   33 , N Foulds  34 , C Graziano  35 , A M Guerrot  36 , M O Hashem  13 , S Heide  7 , D Heron  7 , S E Hickey  37   38 , S M J Hopman  39 , A Kattentidt-Mouravieva  40 , J Kerkhof  41 , J S Klein Wassink-Ruiter  42 , E C Kurtz-Nelson  29   43 , K Kušíková  44 , M Kvarnung  17 , F Lecoquierre  36 , G S Leszinski  21 , L Loberti  23   45 , P L Magoulas  46 , F Mari  23 , I Maystadt  47 , G Merla  48   49 , J M Milunsky  50 , S Moortgat  47 , G Nicolas  36 , M O ' Leary  51 , S Odent  28   52 , J R Ozmore  53 , K Parbhoo  37   54 , R Pfundt  2 , M Piccione  55   56 , A M Pinto  23 , B Popp  57 , A Putoux  24 , H L Rehm  51 , A Reis  8   9 , A Renieri  23   45 , J A Rosenfeld  46   58 , M Rossi  24 , E Salzano  55 , P Saugier-Veber  36 , M Seri  26 , G Severi  26 , F M Sonmez  59 , G Strobl-Wildemann  60 , K E Stuurman  61 , E Uctepe  62 , H Van Esch  63 , G Vitetta  26 , B B A de Vries  2 , D Wahl  64 , T Wang  30   65   66   67 , P Zacher  68 , K R Heitink  69 , F G Ropers  70 , D Steenbeek  71 , T Rybak  72 , G W E Santen  1
Affiliations

ARID1B-related disorder in 87 adults: Natural history and self-sustainability

P J van der Sluijs et al. Genet Med Open. .

Abstract

Purpose: ARID1B is one of the most frequently mutated genes in intellectual disability cohorts. Thus, far few adult-aged patients with ARID1B-related disorder have been described, which limits our understanding of the disease's natural history and our ability to counsel patients and their families.

Methods: Data on patients aged 18+ years with ARID1B-related disorder were collected through an online questionnaire completed by clinicians and parents.

Results: Eighty-seven adult patients with ARID1B were included. Cognitive functioning ranged from borderline to severe intellectual disability. Patients identified through the genetic workup of their child were either mosaic or had a variant in exon 1. New clinical features identified in this population are loss of skill (16/64, 25%) and recurrent patella luxation (12/45, 32%). Self-sustainability data showed that 88% (45/51) could eat independently, and 16% (7/45) could travel alone by public transport. Facial photo analysis showed that patients' photographs taken at different ages clustered consistently, separate from matched controls.

Conclusion: The ARID1B spectrum is broad, and as patients age, there is a significant shift in the medical aspects requiring attention. To address the changing medical needs with increasing age, we have formulated recommendations to promote timely intervention in an attempt to mitigate disease progression.

Keywords: ARID1B; Adult; Coffin–Siris syndrome; Developmental delay; Intellectual disability.

PubMed Disclaimer

Conflict of interest statement

Jill A. Rosenfeld: The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing completed at Baylor Genetics Laboratories. Evan E. Eichler is a scientific advisory board (SAB) member of Variant Bio, Inc. All other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
General characteristicts of the adultARID1Bpopulation. A. Facial photos of ARID1B patients. B. ARID1B transcript with pathogenic variants identified in our patients. C. Survival plot for death n = 87. Histogram of the SDS of (D) Birthweight, n = 53; (E) Height, n = 69; (F) weight for length, n = 55; (G) OFC, n = 55. H. Distribution of ID severity n = 87. I. IQ score n = 32. Cumulative distribution of developmental milestones (J) sitting, n = 61; (K) walking, n = 74; (L) first words, n = 63; (M) toilet trained stool, n = 44. ∗Percentiles of mortality are based on data derived from the Human Mortality database as reported by Beltrán-Sánchez et al and Verguet et al. Percentiles of developmental milestones are based on normative data of children without developmental delay., ID, intellectual disability; IQ, intellectual quotient; SDS, standard deviation score.
Figure 1
Figure 1
General characteristicts of the adultARID1Bpopulation. A. Facial photos of ARID1B patients. B. ARID1B transcript with pathogenic variants identified in our patients. C. Survival plot for death n = 87. Histogram of the SDS of (D) Birthweight, n = 53; (E) Height, n = 69; (F) weight for length, n = 55; (G) OFC, n = 55. H. Distribution of ID severity n = 87. I. IQ score n = 32. Cumulative distribution of developmental milestones (J) sitting, n = 61; (K) walking, n = 74; (L) first words, n = 63; (M) toilet trained stool, n = 44. ∗Percentiles of mortality are based on data derived from the Human Mortality database as reported by Beltrán-Sánchez et al and Verguet et al. Percentiles of developmental milestones are based on normative data of children without developmental delay., ID, intellectual disability; IQ, intellectual quotient; SDS, standard deviation score.
Figure 1
Figure 1
General characteristicts of the adultARID1Bpopulation. A. Facial photos of ARID1B patients. B. ARID1B transcript with pathogenic variants identified in our patients. C. Survival plot for death n = 87. Histogram of the SDS of (D) Birthweight, n = 53; (E) Height, n = 69; (F) weight for length, n = 55; (G) OFC, n = 55. H. Distribution of ID severity n = 87. I. IQ score n = 32. Cumulative distribution of developmental milestones (J) sitting, n = 61; (K) walking, n = 74; (L) first words, n = 63; (M) toilet trained stool, n = 44. ∗Percentiles of mortality are based on data derived from the Human Mortality database as reported by Beltrán-Sánchez et al and Verguet et al. Percentiles of developmental milestones are based on normative data of children without developmental delay., ID, intellectual disability; IQ, intellectual quotient; SDS, standard deviation score.
Figure 2
Figure 2
Survival analysis of features developing later in life in adultARID1Bpatients. Kaplan-Meier plot for the age of (A) onset first seizure, n = 80; (B) loss of skill, n = 54; (C) diabetes mellitus, type 2, n = 53; (D) hypothyroidism, n = 51; (E) nephrolithiasis, n = 38; (F) first patella luxation, n = 43.
Figure 2
Figure 2
Survival analysis of features developing later in life in adultARID1Bpatients. Kaplan-Meier plot for the age of (A) onset first seizure, n = 80; (B) loss of skill, n = 54; (C) diabetes mellitus, type 2, n = 53; (D) hypothyroidism, n = 51; (E) nephrolithiasis, n = 38; (F) first patella luxation, n = 43.
See this image and copyright information in PMC

References

    1. Hoyer J., Ekici A.B., Endele S., et al. Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability. Am J Hum Genet. 2012;90(3):565–572. doi: 10.1016/j.ajhg.2012.02.007. - DOI - PMC - PubMed
    1. Wright C.F., Fitzgerald T.W., Jones W.D., et al. Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data. Lancet. 2015;385(9975):1305–1314. doi: 10.1016/S0140-6736(14)61705-0. - DOI - PMC - PubMed
    1. Gillentine M.A., Wang T., Eichler E.E. Estimating the prevalence of de novo monogenic neurodevelopmental disorders from large cohort studies. Biomedicines. 2022;10(11) doi: 10.3390/biomedicines10112865. - DOI - PMC - PubMed
    1. Valencia A.M., Sankar A., van der Sluijs P.J., et al. Landscape of mSWI/SNF chromatin remodeling complex perturbations in neurodevelopmental disorders. Nat Genet. 2023;55(8):1400–1412. doi: 10.1038/s41588-023-01451-6. - DOI - PMC - PubMed
    1. van der Sluijs P.J., Jansen S., Vergano S.A., et al. The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin-Siris syndrome. Genet Med. 2019;21(6):1295–1307. doi: 10.1038/s41436-018-0330-z. - DOI - PMC - PubMed

LinkOut - more resources