Supplementary 1

1

De Lange, C. Sur un type nouveau de degenerescence (typus Amsterlodamensis). Arch. Med. Enfants 36, 713–719 (1933).

2

Kline, A. D. et al. Natural history of aging in Cornelia de Lange syndrome. Am. J. Med. Genet. C Semin. Med.
Genet. 145C, 248–260 (2007).
Este es un trabajo de referencia que describe los signos y síntomas de los pacientes con SCdL.

3

Huisman, S. A. et al. Phenotypes and genotypes in 51 individuals with SMC1A variants. Am. J. Med. Genet. 173A, 2108–2125

4

Yuan, B. et al. Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes. J. Clin. Invest.  125, 636–651 (2015)

5

Saunier, C. et al. Expanding the phenotype associated with NAA10-related N-terminal acetylation deficiency.Hum. Mutat. 37, 755–764 (2016).

6

Hennekam, R. C. What to call a syndrome. Am. J. Med.Genet. 143A, 1021–1024 (2007).

7

Santen, G. W. et al. Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients.Hum. Mutat. 34, 1519–1528 (2013).

8

Fergelot, P. et al. Phenotype and genotype in 52 patients with Rubinstein-Taybi syndrome caused by EP300 mutations. Am. J. Med. Genet. 170A, 3069–3082 (2016).

9

Sousa, S. B. & Hennekam, R. C. Phenotype and genotype in Nicolaides-Baraitser syndrome. Am. J. Med. Genet. C Semin. Med. Genet. 166, 302–314 (2014).

10

Bhuiyan, Z. A. et al. Genotype-phenotype correlations of 39 patients with Cornelia de Lange syndrome: the Dutch experience. J. Med. Genet. 43, 568–575 (2006).
Este trabajo es el primero que correlaciona con detalle las características físicas y del comportamiento con los hallazgos de los estudios genéticos en una serie de pacientes con SCdL..

11

Selicorni, A. et al. Clinical score of 62 Italian patients with Cornelia de Lange syndrome and correlations with the presence and type of NIPBL mutation. Clin. Genet. 72, 98–108 (2007).

12

Cereda, A. et al. A new prognostic index of severity of intellectual disabilities in Cornelia de Lange syndrome. Am. J. Med. Genet. C Semin. Med. Genet. 172, 179–189 (2016).

13

Krantz, I. D. et al. Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B. Nat. Genet. 36, 631–635 (2004).

14

Tonkin, E. T., Wang, T. J., Lisgo, S., Bamshad, M. J. & Strachan, T. NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome. Nat. Genet. 36, 636–641 (2004).
Los trabajos 13 y 14 son los primeros que demuestran que el SCdL es una cohesinopatía.

15

Musio, A. et al. X-Linked Cornelia de Lange syndrome owing to SMC1L1 mutations. Nat. Genet. 38, 528–530 (2006).

16

Deardorff, M. A. et al. Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of Cornelia de Lange syndrome with predominant mental retardation. Am. J. Hum. Genet. 80, 485–494 (2007).

17

Deardorff, M. A. et al. RAD21 mutations cause a human cohesinopathy. Am. J. Hum. Genet. 90, 1014–1027 (2012).

18

Olley, G. et al. BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange-like syndrome. Nat. Genet. 50, 329–332 (2018).

19

chromosomal proteins that prevent premature separation of sister chromatids. Cell 91, 35–45 (1997).
Este trabajo describe las primeras proteínas que influyen en la separación de las cromátides hermanas.

20

Kagey, M. H. et al. Mediator and cohesin connect gene expression and chromatin architecture. Nature 467, 430–435 (2010).

21

Watrin, E., Kaiser, F. J. & Wendt, K. S. Gene regulation and chromatin organization: relevance of cohesin mutations to human disease. Curr. Opin. Genet. Dev. 37, 59–66 (2016).

22

Kamada, K. & Barillà, D. Combing chromosomal DNA mediated by the SMC complex: structure and mechanisms. Bioessays 40, 17000166 (2018).

23

Huisman, S. A., Redeker, E. J. W., Maas, S. M., Mannens, M. M. & Hennekam, R. C. High rate of mosaicism in individuals with Cornelia de Lange syndrome. J. Med. Genet. 50, 339–344 (2013).
Este trabajo es el primero que demuestra que en un número importante de pacientes con SCdL la mutación de NIPBL se encuentra únicamente en tejidos distintos a la sangre.

24

Ansari, M. et al. Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism.
J. Med. Genet. 51, 659–668 (2014).

25

Gillis, L. A. et al. NIPBL mutational analysis in
120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations. Am. J. Hum. Genet. 75, 610–623 (2004).

26

Yan, J. et al. Mutational and genotype-phenotype correlation analyses in 28 Polish patients with Cornelia de Lange syndrome. Am. J. Med. Genet. 140A, 1531–1541 (2006).

27

Ratajska, M. et al. Cornelia de Lange syndrome case due to genomic rearrangements including NIPBL. Eur. J. Med. Genet. 53, 378–382 (2010).

28

Russo, S. et al. Intragenic and large NIPBL rearrangements revealed by MLPA in Cornelia de Lange patients. Eur. J. Hum. Genet. 20, 734–741 (2012).

29

Borck, G. et al. Incidence and clinical features of X-linked Cornelia de Lange syndrome due to SMC1L1 mutations. Hum. Mutat. 28, 205–206 (2007).

30

Jansen, S. et al. De novo loss-of-function mutations
in X-linked SMC1A cause severe ID and therapy-resistant epilepsy in females: expanding the phenotypic spectrum. Clin. Genet. 90, 413–419 (2016).

31

Symonds, J. D. et al. Heterozygous truncation mutations of the SMC1A gene cause a severe early onset epilepsy with cluster seizures in females:detailed phenotyping of 10 new cases. Epilepsia 58, 565–575 (2017).

32

Carrel, L. & Willard, H. F. X-Inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 434, 400–404 (2005).

33

Gil-Rodríguez, M. C. et al. De novo heterozygous mutations in SMC3 cause a range of Cornelia de
Lange syndrome-overlapping phenotypes. Hum. Mutat. 36, 454–462 (2015).

34

McKay, M. J. et al. Sequence conservation of the rad21 Schizosaccharomyces pombe DNA double- strand break repair gene in human and mouse. Genomics 36, 305–315 (1996).

35

Boyle, M. I., Jespersgaard, C., Nazaryan, L., Bisgaard, A. M. & Tümer, Z. A novel RAD21 variant associated with intrafamilial phenotypic variation in Cornelia de Lange syndrome — review of the literature. Clin. Genet. 91, 647–649 (2017).

36

Bonora, E. et al. Mutations in RAD21 disrupt regulation of APOB in patients with chronic intestinal pseudo-obstruction. Gastroenterology 148, 771–782 (2015).

37

Hnisz, D. et al. Super-enhancers in the control of cell identity and disease. Cell 155, 934–947 (2013).

38

Deardorff, M. A. et al. HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. Nature 489, 313–317 (2012).

39

Harakalova, M. et al. X-Exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face. J. Med. Genet. 49, 539–543 (2012).

40

Feng, L., Zhou, D., Zhang, Z., Liu, Y. & Yang, Y. Exome sequencing identifies a de novo mutation in HDAC8 associated with Cornelia de Lange syndrome. J. Hum. Genet. 59, 536–539 (2014).

41

Kaiser, F. J. et al. Loss-of-function HDAC8 mutations cause a phenotypic spectrum of Cornelia de Lange syndrome-like features, ocular hypertelorism, large fontanelle and X-linked inheritance. Hum. Mol. Genet. 23, 2888–2900 (2014).

42

Parenti, I. et al. Expanding the clinical spectrum
of the ‘HDAC8-phenotype’ — implications for molecular diagnostics, counseling and risk prediction. Clin. Genet. 89, 564–573 (2016).

43

Parenti, I. et al. Broadening of cohesinopathies: exome sequencing identifies mutations in ANKRD11 in two patients with Cornelia de Lange-overlapping phenotype. Clin. Genet. 89, 74–81 (2016).

44

Woods, S. A. et al. Exome sequencing identifies a novel EP300 frame shift mutation in a patient with features that overlap Cornelia de Lange syndrome. Am. J. Med. Genet. 164A, 251–258 (2014).

45

Izumi, K. et al. Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin. Nat. Genet. 47, 338–344 (2015).

46

Baquero-Montoya, C. et al. Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation. Eur. J. Med. Genet. 57, 503–509 (2014).

47

Weichert, J., Schröer, A., Beyer, D. A., Gillessen-Kaesbach, G. & Stefanova, I. Cornelia de Lange syndrome: antenatal diagnosis in two consecutive pregnancies due to rare gonadal mosaicism of NIPBL gene mutation. J. Matern. Fetal Neonatal Med. 24, 978–982 (2011).

48

Slavin, T. P. et al. Germline mosaicism in Cornelia de Lange syndrome. Am. J. Med. Genet. 158A, 1481–1485 (2012).

49

Jackson, L., Kline, A. D., Barr, M. A. & Koch, S. de Lange syndrome: a clinical review of 310 individuals. Am. J. Med. Genet. 47, 940–946 (1993).
Este trabajo es el primero que demuestra que en un número importante de pacientes con SCdL la mutación de NIPBL se encuentra únicamente en tejidos distintos a la sangre.

50

Dempsey, M. A. et al. Molecular confirmation of nine cases of Cornelia de Lange syndrome diagnosed prenatally. Prenat. Diagn. 34, 163–167 (2014).

51

Clark, D. M. et al. Prenatal profile of Cornelia de Lange syndrome (CdLS): a review of 53 pregnancies. Am. J. Med. Genet. 158A, 1848–1856 (2012).

52

Stevic, M., Milojevic, I., Bokun, Z. & Simic, D. Unpredictable drug reaction in a child with Cornelia de Lange syndrome. Int. J. Clin. Pharm. 37, 1–3 (2015).

53

Moretto, A. et al. Sedation and general anesthesia for patients with Cornelia De Lange syndrome: a case series. Am. J. Med. Genet. C Semin. Med. Genet. 172, 222–228 (2016).

54

Kline, A. D., Barr, M. & Jackson, L. G. Growth manifestations in the Brachmann-de Lange syndrome. Am. J. Med. Genet. 47, 1042–1049 (1993).

55

Kousseff, B. G., Thomson-Meares, J., Newkirk, P. & Root, A. W. Physical growth in Brachmann-de Lange syndrome. Am. J. Med. Genet. 47, 1050–1052 (1993).

56

De Graaf, M. et al. Successful growth hormone therapy in Cornelia de Lange syndrome. J. Clin. Res. Pediatr. Endocrinol. 9, 366–370 (2017).

57

Romano, C. et al. European Society for Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for the evaluation and treatment of gastrointestinal and nutritional complications in children with neurological impairment. J. Pediatr. Gastroenterol. Nutr. 65, 242–264 (2017).

58

Toker, A. S., Ay, S., Yeler, H. & Sezgin, I. Dental findings in Cornelia de Lange syndrome. Yonsei Med. J. 50, 289–292 (2009).

59

Mariani, M. et al. Adolescents and adults affected by Cornelia de Lange syndrome: a report of 73 Italian patients. Am. J. Med. Genet. C Semin. Med. Genet. 172, 206–213 (2016).
Este trabajo es el primero que incluyó una revisión detallada de las características físicas y de comportamiento de adultos con SCdL.

60

Mouradian, W. E. The face of a child: children’s oral health and dental education. J. Dent. Educ. 65, 821–831 (2001).

61

Scarpelli, A. C. et al. Cornelia De Lange syndrome:
a case report of a Brazilian boy. Cleft Palate Craniofac. J. 48, 490–493 (2011).

62

Jyonouchi, S., Orange, J., Sullivan, K. E., Krantz, I. & Deardorff, M. Immunologic features of Cornelia de Lange syndrome. Pediatrics 132, e484–e489 (2013).

63

Cavalleri, V. et al. Thrombocytopenia and Cornelia de Lange syndrome: still an enigma? Am. J. Med. Genet. 170A, 130–134 (2016).

64

 Lambert, M. P. et al. The incidence of thrombocytopenia in children with Cornelia de Lange syndrome. Am. J. Med. Genet. 155A, 33–37 (2011).

65

Collis, L., Moss, J., Jutley, J., Cornish, K. & Oliver, C. Facial expression of affect in children with Cornelia de Lange syndrome. J. Intellect. Disabil. Res. 52, 207–215 (2008).

66

Malviya, S., Voepel-Lewis, T., Burke, C., Merkel, S. & Tait, A. R. The revised FLACC observational pain tool: improved reliability and validity for pain assessment in children with cognitive impairment. Paediatr. Anaesth. 16, 258–265 (2006).

67

Beck, B. & Fenger, K. Mortality, pathological findings and causes of death in the de Lange syndrome. Acta Paediatr. Scand. 74, 765–769 (1985).

68

Feingold, M. & Lin, A. E. Familial Brachmann-de Lange syndrome: further evidence for autosomal dominant inheritance and review of the literature. Am. J. Med. Genet. 47, 1064–1067 (1993).

69

Chodirker, B. N. & Chudley, A. E. Male-to-male transmission of mild Brachmann-de Lange syndrome. Am. J. Med. Genet. 52, 331–333 (1994).

70

McKenney, R. R., Elder, F. F., Garcia, J. & Northrup, H. Brachmann-de Lange syndrome: autosomal dominant inheritance and male-to-male transmission. Am. J. Med. Genet. 66, 449–452 (1996).

71

Quint, E. H. Menstrual and reproductive issues in adolescents with physical and developmental disabilities. Obstetr. Gynecol. 124, 367–375 (2014).

72

American College of Obstetricians and Gynecologists. Menstrual manipulation for adolescents with physical and developmental disabilities. ACOG Committee Opinion 668, August 2016 (ACOG, 2016).

73

Schrier, S. A. et al. Causes of death and autopsy findings in a large study cohort of individuals with Cornelia de Lange syndrome and review of the literature. Am. J. Med. Genet. 155A, 3007–3024 (2011).

74

Oliver, C. et al. Cornelia de Lange syndrome: extending the physical and psychological phenotype. Am. J. Med. Genet. 152A, 1127–1135 (2010).

75

McVary, K. T. BPH: epidemiology and comorbidities. Am. J. Manag. Care 12, S122–S128 (2006).

76

McVary, K. T. et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J. Urol. 187, 358–359 (2012).

77

World Health Organization. WHO Guidelines for screening and treatment of precancerous lesions for cervical cancer prevention (WHO, 2013).

78

World Health Organization. WHO position paper on mammography screening (WHO, 2014).

79

Filippi, G. The de Lange syndrome. Report of 15 cases. Clin. Genet. 35, 343–363 (1989).

80

Wick, M. R., Simmons, P. S., Ludwig, J. & Kleinberg, F. Duodenal obstruction, annual pancreas, and horseshoe kidney in an infant with Cornelia de Lange syndrome. Minn. Med. 65, 539–541 (1982).

81

Mende, R. H., Drake, D. P., Olomi, R. M. & Hamel, B. C. J. Cornelia de Lange syndrome: a newborn with imperforate anus and a NIPBL mutation. Case Rep. Genet. 2012, 247683 (2012).

82

Cunniff, C. et al. Congenital diaphragmatic hernia in the Brachmann-de Lange syndrome. Am. J. Med. Genet. 47, 1018–1021 (1993).

83

Hosokawa, S. et al. Brachmann-de Lange syndrome with congenital diaphragmatic hernia and NIPBL gene mutation. Congenit. Anom. (Kyoto) 50, 129–132 (2010).

84

Husain, K., Fitzgerald, P. & Lau, G. Cecal volvulus in the Cornelia de Lange syndrome. J. Pediatr. Surg. 29, 1245–1247 (1994).

85

Casaccia, G., Seymandi, P. L., Odone, M. G. & Catalano, O. A. Caecal volvulus in Cornelia de Lange syndrome: is its prevention possible? J. Paediatr. Child Health 45, 391–396 (2009).

86

Clermidi, P., Abadie, V., Campeotto, F. & Irtan, S. Sigmoid volvulus: an underestimated cause of intestinal obstruction in Cornelia de Lange syndrome. J. Pediatr. 167, 941–942 (2015).

87

Macchini, F. et al. Coeliac disease and Cornelia de Lange syndrome: lack of association. Acta Paediatr. 96, 1518–1520 (2007).

88

Bull, M. J., Fitzgerald, J. F., Heifetz, S. A. & Brei, T. J. Gastrointestinal abnormalities: a significant cause of feeding difficulties and failure to thrive in Brachmann- de Lange syndrome. Am. J. Med. Genet. 47, 1029–1034 (1993).

89

Sommer, A. Occurrence of the Sandifer complex in the Bachmann-de Lange syndrome. Am. J. Med. Genet. 47, 1026–1028 (1993).

90

Berney, T., Ireland, M. & Burn, J. Behavioral phenotype of Cornelia de Lange syndrome. Arch. Dis. Child. 81, 333–336 (1999).

91

Nizon, M. et al. A series of 38 novel germline and somatic mutations of NIPBL in Cornelia de Lange syndrome. Clin. Genet. 89, 584–589 (2016).

92

Luzzani, S., Macchini, F., Valade, A., Milani, D. & Selicorni, A. Gastroesophageal reflux and Cornelia de Lange syndrome: typical and atypical symptoms. Am. J. Med. Genet. 119A, 283–287 (2003).

93

Macchini, F. et al. Barrett’s esophagus and Cornelia de Lange syndrome. Acta Paediatr. 99, 1407–1410 (2010).

94

Duvall, G. A. & Walden, D. T. Adenocarcinoma of the esophagus complicating Cornelia de Lange syndrome. J. Clin. Gastroenterol. 22, 131–133 (1996).

95

Fitzgerald, R. C. et al. British Society of Gastroen- terology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut 63, 7–42 (2014).

96

Hassall, E. et al. Long-term maintenance treatment with omeprazole in children with healed erosive oesophagitis: a prospective study. Aliment. Pharmacol. Ther. 35, 368–379 (2012).

97

Wygnanski-Jaffe, T. et al. Ophthalmologic findings in the Cornelia de Lange syndrome. J. AAPOS 9, 407–415 (2005).

98

Nallasamy, S. et al. Ophthalmologic findings in Cornelia de Lange syndrome: a genotype-phenotype correlation study. Arch. Ophthalmol. 124, 552–557 (2006).

99

Avgitidou, G., Cursiefen, C. & Heindl, L. M. Ophthalmological manifestations of Cornelia de Lange syndrome: case report and review of the literature. Ophthalmologe 112, 455–458 (2015).

100

Tychsen, L., Faron, N. & Hoekel, J. Phakic intraocular collamer lens (visian ICL) implantation for correction of myopia in spectacle-aversive special needs children. Am. J. Ophthalmol. 175, 77–86 (2017).

101

Sataloff, R. T., Spiegel, J. R., Hawkshaw, M., Epstein, J. M. & Jackson, L. Cornelia de Lange syndrome. Otolaryngologic manifestations. Arch. Otolaryngol. Head Neck Surg. 116, 1044–1046 (1990).

102

Sasaki, T., Kaga, K., Ohira, Y., Ogawa, Y. & Fukushima, Y. Temporal bone and brain stem histopathological findings in Cornelia de Lange syndrome. Int. J. Pediatr. Otorhinolaryngol. 36, 195–204 (1996).

103

Kim,J.,Kim,E.Y.,Lee,J.S.,Lee,W.S.&Kim,H.N. Temporal bone CT findings in Cornelia de Lange syndrome. Am. J. Neuroradiol. 29, 569–573 (2008).

104

Marchisio, P. et al. Otitis media with effusion and hearing loss in children with Cornelia de Lange syndrome. Am. J. Med. Genet. 146A, 426–432 (2008).

105

Marchisio, P. et al. Audiological findings, genotype and clinical severity score in Cornelia de Lange syndrome. Int. J. Pediatr. Otorhinolaryngol. 78, 1045–1048 (2014).

106

Janek, K. C. et al. Improvement in hearing loss over time in Cornelia de Lange syndrome. Int. J. Pediatr. Otorhinolaryngol. 87, 203–207 (2016).

107

Hyman, P., Oliver, C. & Hall, S. Self-injurious behavior, self-restraint, and compulsive behaviors in Cornelia de Lange syndrome. Am. J. Ment. Retard. 107, 146–154 (2002).

108

Sakai, Y., Watanabe, T. & Kaga, K. Auditory brainstem responses and usefulness of hearing aids in hearing impaired children with Cornelia de Lange syndrome. Int. J. Pediatr. Otorhinolaryngol. 66, 63–69 (2002).

109

Nelson, L., Moss, J. & Oliver, C. A. Longitudinal follow- up study of affect in children and adults with Cornelia de Lange syndrome. Am. J. Intellect. Dev. Disabil. 119, 235–252 (2014).

110

Hamilton, J., Clement, W. A. & Kubba, H. Otolaryngological presentations of Cornelia de Lange syndrome. Int. J. Pediatr. Otorhinolaryngol. 78, 1548–1550 (2014).

111

Pulec, J. L. & Saadat, D. Multichannel cochlear implantation in a child with Brachmann-De Lange syndrome. Otolaryngol. Head Neck Surg. 113, 641–643 (1995).

112

Brietzke, S. E. et al. Clinical consensus statement: pediatric chronic rhinosinusitis. Otolaryngol. Head Neck Surg. 151, 542–553 (2014).

113

Rosenfeld, R. M. et al. Clinical practice guidelines (update): adult sinusitis. Otolaryngol. Head Neck Surg. 152, S1–S39 (2015).

114

Ashahi, Y. et al. General anaesthesia with and without intubation for patients with Cornelia de Lange syndrome. South. Afr. J. Anaesth. Analg. 15, 32–34 (2009).

115

Mehta, D. et al. Characterization of limb differences in children with Cornelia de Lange Syndrome. Am. J. Med. Genet. C Semin. Med. Genet. 172, 155–162 (2016).

116

Halal, F. & Preus, M. The hand profile on de Lange syndrome: diagnostic criteria. Am. J. Med. Genet. 3, 317–323 (1979).

117

Braddock, R. et al. Radiologic features in Brachmann- de Lange syndrome. Am. J. Med. Genet. 47, 106–1013 (1993).

118

Roposch, A. et al. Orthopaedic manifestations of Brachmann-de Lange syndrome: a report of 34 patients. J. Pediatr. Orthop. B 13, 118–122 (2004).

119

Barboni, C. et al. A new report of Cornelia de Lange syndrome associated with split hand and feet. Am. J. Med. Genet. 158A, 2953–2955 (2012).

120

Ruzbarsky, J. J., Scher, D. & Dodwell, E. Toe walking: causes, epidemiology, assessment and treatment. Curr. Opin. Pediatr. 28, 40–46 (2016).

121

Bettini, L. R. et al. Cervical spine malformation in Cornelia de Lange syndrome: a report of three patients. Am. J. Med. Genet. 164A, 1520–1524 (2014).

122

Torres, M. D., Calvo, E., Fernandez Espla, F. & Gilsanz, F. Anesthetic management of an adult patient with Cornelia de Lange syndrome. Minerva Anesthesiol. 76, 229–231 (2010).

123

Pavlidis, E., Cantalupo, G., Bianchi, S., Piccolo, B. & Pisani, F. Epileptic features in Cornelia de Lange syndrome: case report and literature review. Brain Dev. 36, 837–843 (2014).

124

Verrotti, A. et al. Epilepsy in patients with Cornelia de Lange syndrome: a clinical series. Seizure 22, 356–359 (2013).

125

Nechay, A., Smulska, N. & Chepiga, L. Anoxic-epileptic seizures in Cornelia de Lange syndrome: case report of epileptic seizures induced by obstructive apnea. Eur. J. Paediatr. Neurol. 10, 142–144 (2006).

126

Fernandez, H. H., Friedman, J. H. & Famiglietti, E. V. Probable Cornelia de Lange syndrome with progressive Parkinsonism and dystonia. Mov. Disord. 15, 749–751 (2000).

127

Chen, Y. W., Hung, P. L., Wu, C. K. & Tseng, P. T. Severe complication of catatonia in a young patient with Hashimoto’s encephalopathy comorbid with Cornelia de Lange syndrome. Kaohsiung J. Med. Sci. 31, 60–61 (2015).

128

Van den Berg, D. L. C. et al. Nipbl interacts with Zfp609 and the integrator complex to regulate cortical neuron migration. Neuron 93, 348–361 (2017).

129

Whitehead, M. T., Nagaraj, U. D. & Pearl, P. L. Neuroimaging features of Cornelia de Lange syndrome. Pediatr. Radiol. 45, 1198–1205 (2015).

130

Vuilleumier, N. et al. Neuropathological analysis of an adult case of the Cornelia de Lange syndrome. Acta Neuropathol. 104, 327–332 (2002).

131

Roshan Lal, T. R. et al. Cornelia de Lange syndrome: correlation of brain MRI findings with behavioral assessment. Am. J. Med. Genet. C Semin. Med. Genet. 172, 190–197 (2016).

132

Mutlu, M., Dilber, B. & Aslan, Y. Cornelia de Lange syndrome associated with thoracic meningocele. Clin. Dysmorphol. 19, 161–163 (2010).

133

Hall, S. S., Arron, K., Sloneem, J. & Oliver, C. Health and sleep problems in Cornelia de Lange Syndrome: a case control study. J. Intellect. Disabil. Res. 52, 458–468 (2008).

134

Stavinoha, R. C. et al. Characterization of sleep disturbance in Cornelia de Lange Syndrome. Int. J. Pediatr. Otorhinolaryngol. 75, 215–218 (2011).

135

Rajan, R. et al. Insomnia in Cornelia de Lange syndrome. Int. J. Pediatr. Otorhinolaryngol. 76, 972–975 (2012).

136

Zambrelli, E. et al. Sleep disorders in Cornelia de Lange syndrome. Am. J. Med. Genet. C Semin. Med. Genet. 172, 214–221 (2016).

137

Wulffaert, J. et al. Simultaneous analysis of the behavioral phenotype, physical factors, and parenting stress in people with Cornelia de Lange syndrome. J. Intellect. Disabil. Res. 53, 604–619 (2009).

138

Ajmone, P. F. et al. Communication, cognitive development and behavior in children with Cornelia de Lange syndrome (CdLS): preliminary results. Am. J. Med. Genet. Neuropsychiatr. Genet. 165B, 223–229 (2014).

139

Reid, D., Moss, J., Nelson, L., Groves, L. & Oliver, C. Executive functioning in Cornelia de Lange syndrome: domain asynchrony and age related performance. J. Neurodev. Dis. 9, 29 (2017).

140

Johnson, V. Executive function and decision making in Cornelia de Lange syndrome. PhD thesis, Univ. Birmingham (2015).

141

Joosten, A. V. & Bundy, A. C. Sensory processing and stereotypical and repetitive behaviour in children with autism and intellectual disability. Aust. Occup. Ther. J. 57, 366–372 (2010).

142

Baker, A. E. Z., Lane, A., Angley, M. T. & Young, R. L. The relationship between Sensory processing patterns and behavioral responsiveness in autistic disorder: a pilot study. J. Autism Dev. Disord. 38, 867–875 (2008).

143

Bogdashina, O. Sensory perceptual issues in autism and Asperger syndrome: different sensory experiences — different perceptual worlds 2nd edn, (Jessica Kingsley Publishers, London, 2016).

144

Mazurek, M. O. et al. Anxiety, sensory over- responsivity, and gastrointestinal problems in children with autism spectrum disorders. J. Abnorm. Child Psychol. 41, 165–176 (2013).

145

Mulder, P. A. et al. Development, behavior and autism in individuals with SMC1A variants. J. Child Psychol. Psychiatry (in the press).

146

Engel-Yeger, B., Hardal-Nasser, R. & Gal, E. Sensory processing dysfunctions as expressed among children with different severities of intellectual developmental disabilities. Res. Dev. Disabil. 32, 1770–1775 (2011).

147

Cascio, C. J., Lorenzi, J. & Baranek, G. T. Self-reported pleasantness ratings and examiner-coded defensiveness in response to touch in children with ASD: effects of stimulus material and bodily location. J. Autism Dev. Disord. 46, 1528–1537 (2016).

148

Moss, J., Fitzpatrick, D., Welham, A., Penhallow, J. & Oliver, C. Genotype-phenotype correlations in Cornelia de Lange syndrome: behavioral characteristics and changes with age. Am. J. Med. Genet. 173A, 1566–1574 (2017).

149

Nakanishi, M. et al. Investigation of autistic features among individuals with mild to moderate Cornelia de Lange syndrome. Am. J. Med. Genet. 158A, 1841–1847 (2002).

150

Moss, J. et al. Prevalence of autism spectrum phenomenology in Cornelia de Lange and Cri du Chat syndromes. Am. J. Ment. Retard. 113, 278–291 (2008).

151

Moss, J. et al. Social behavior and characteristics of Autism Spectrum Disorder in Angelman, Cornelia de Lange and Cri du Chat syndromes. Am. J. Intellect. Dev. Disabil. 118, 262–283 (2013).

152

Richards, C., Moss, J., O’Farrell, L., Kaur, G. & Oliver, C. Social anxiety in Cornelia de Lange syndrome. J. Autism Dev. Disord. 39, 1155–1162 (2009).

153

Crawford, H., Moss, J., McCleery, J. P., Anderson, G. M. & Oliver, C. Face scanning and spontaneous emotion preference in Cornelia de Lange syndrome and Rubinstein-Taybi syndrome. J. Neurodev. Dis. 7, 22 (2015).

154

Srivastava, S. et al. Autism traits in children and adolescents with Cornelia de Lange syndrome. Am. J. Med. Genet. 164A, 1400–1410 (2014).

155

Cochran, L., Moss, J., Nelson, L. & Oliver, C. Contrasting age related changes in autism spectrum dis- order phenomenology in Cornelia de Lange, Fragile X,and Cri du Chat syndromes: results from a 2.5 year follow-up. Am. J. Med. Genet. C Semin. Med. Genet. 169, 188–197 (2015).

156

Huisman, S. A. et al. Self-injurious behavior. Neurosci. Biobehav. Rev. 84, 483–491 (2018). This paper provides an overview of self-injurious behaviour and stresses the differences between various syndromes, including CdLS.

157

Berkson, G. & Tupa, M. Early development of stereotyped and self-injurious behaviors. J. Early Interv. 23, 1–19 (2000).

158

Oliver, C., Sloneem, J., Hall, S. & Arron, K. Self- injurious behaviour in Cornelia de Lange syndrome: 1. Prevalence and phenomenology. J. Intellect. Disabil. Res. 53, 575–589 (2009).

159

Richards, C., Groves, L., Jones, C., Moss, J. & Oliver, C. Prevalence of autism spectrum disorder phenomenology in genetic disorders: a systematic review and meta-analysis. Lancet Psychiatry 2, 909–916 (2015).

160

McCracken, J. T. et al. Risperidone in children with autism and serious behavioral problems. N. Engl. J. Med. 347, 314–321 (2002).

161

Goldman, S. et al. Motor stereotypies in children with autism and other developmental disorders. Dev. Med. Child Neurol. 51, 30–38 (2008).

162

Moss, J., Oliver, C., Arron, K., Burbridge, C. & Berg, K. The prevalence and phenomenology of repetitive behavior in genetic syndromes. J. Autism Dev. Disord. 39, 572–588 (2009).

163

Leekam, S., Prior, M. R. & Uljarevic, M. Restricted and repetitive behaviors in autism spectrum disorders:
a review of research in the last decade. Psych. Bull. 137, 562–593 (2011).

164

King, B. H. et al. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Arch. Gen. Psychiatry 66, 583–590 (2009).

165

Grados, M. A., Alvi, M. H. & Srivastava, S. Behavioral and psychiatric manifestations in Cornelia de Lange syndrome. Curr. Opin. Psychiatry 30, 92–96 (2017).

166

Basile, E., Villa, L., Selicorni, A. & Molteni, M. The behavioural phenotype of Cornelia de Lange syndrome: a study of 56 individuals. J. Intellect. Disabil. Res. 51, 671–681 (2007).

167

Moss, J. et al. A comparative study of sociability and selective mutism in autism spectrum disorder, Angelman, Cornelia de Lange, Fragile X and Rubinstein-Taybi syndromes. Am. J. Intellect. Dev. Disabil. 121, 465–486 (2016).

168

Crawford, H., Waite, J. & Oliver, C. Diverse profiles of anxiety related disorders in fragile X, Cornelia de Lange and Rubinstein-Taybi syndromes. Autism Dev. Disord. 47, 3728–3740 (2017).

169

Mulder, P. A. et al. Behaviour in Cornelia de Lange syndrome: a systematic review. Dev. Med. Child Neurol. 59, 361–366 (2017). Este trabajo describe las características específicas del comportamiento de pacientes con SCdL.

170

Sarimski, K. Analysis of intentional communication in severely handicapped children with Cornelia de Lange syndrome. J. Commun. Disord. 35, 483–500 (2002).

171

Hassiotis, A. et al. Randomized, single-blind, controlled trial of a specialist behavior therapy team for challenging behavior in adults with intellectual disabilities. Am. J. Psychiatry 166, 1278–1285 (2009).

172

Oliver, C., Berg, K., Moss, J., Arron, K. & Burbidge, C. Delineation of behavioural phenotypes in genetic syndromes. Comparison of autism spectrum disorder, affect and hyperactivity. J. Autism Dev. Disord. 41, 1019–1032 (2011).
Este trabajo describe las características específicas del trastorno del espectro autista (TEA) en varios síndromes, incluyendo el SCdL.

173

Moss, J., Magiati, I., Howlin, P. & Oliver, C. Characteristics of autism spectrum disorder in Cornelia de Lange syndrome. J. Child Psychol. Psychiatry 53, 883–891 (2012).

174

Sarimski, K. Communication, social-emotional development and parenting stress in Cornelia- de-Lange syndrome. J. Intellect. Disabil. Res. 41, 70–75 (1997).

175

Arron, K., Oliver, C., Berg, K., Moss, J. & Burbidge, C. Prevalence and phenomenology of self-injurious and aggressive behaviour in genetic syndromes. J. Intellect. Disabil. Res. 55, 109–120 (2011).

176

Goodban, M. T. Survey of speech and language skills with prognostic indicators in 116 patients with Cornelia de Lange Syndrome. Am. J. Med. Genet. 47, 1059–1063 (1993).

177

Lorusso, M. L. et al. Indicators of theory of mind in narrative production: a comparison between individuals with genetic syndromes and typically developing children. Clin. Linguist. Phon. 21, 37–53 (2007).

178

Snell, M. E. et al. Twenty years of communication intervention research with individuals who have severe intellectual and developmental disabilities. Am. J. Intellect. Dev. Disabil. 115, 364–380 (2010).

179

Fraser, W. I. & Campbell, B. M. A study of six cases of De Lange Amsterdam dwarf syndrome with special attention to voice, speech, and language characteristics. Dev. Med. Child Neurol. 20, 189–198 (1978).

180

Verpoorten, R. A. W. Communicatie met verstandelijk gehandicapte autisten: een multi-dimensioneel communicatiemodel. Ned. T. Zorg Verstand. Gehand. 22, 106–120 (1996).

181

Romski, M. et al. Randomized comparison of augmented and nonaugmented language interventions for toddlers with developmental delays and their parents. J. Speech Lang. Hear. Res. 53, 350–364 (2010).

182

Wilkinson, K. M. & Hennig, S. The state of research and practice in augmentative and alternative communication for children with developmental/ intellectual disabilities. Ment. Retard. Dev. Disabil. Res. Rev. 13, 58–69 (2007).

183

Porter, J., Ouvry, C., Morgan, M. & Downs, C. Interpreting the communication of people with profound and multiple learning difficulties. Br. J. Learn. Disabil. 29, 12–16 (2001).

184

Dobson, S., Upadhyaya, S. & Stanley, B. Using an interdisciplinary approach to training to develop the quality of communication with adults with profound learning disabilities by care staff. Int. J. Lang. Commun. Dis. 37, 41–57 (2002).

185

Wierzba, J., Mazurkiewicz-Bełdzińska, M., Bełdzińska-Brudło,J.,Potaz ̇,P.&Banach,P. Challenges of caring for a patient with a rare disease — as demonstrated by Cornelia de Lange Syndrome. Dev. Period Med. 19, 511–515 (2015).

186

January, K. et al. Benefits and limitations of a multidisciplinary approach to individualized management of Cornelia de Lange syndrome and related diagnoses. Am. J. Med. Genet. C Semin. Med. Genet. 172, 237–245 (2016).

187

Mikołajewska, E. Interdisciplinary therapy in Cornelia de Lange syndrome — review of the literature.
Adv. Clin. Exp. Med. 22, 571–577 (2013).

188

Ailey, S. H., Brown, P. J. & Ridge, C. M. Improving hospital care of patients with intellectual and developmental disabilities. Disabil. Health J. 10, 169–172 (2017).

189

Fisher, K., Haagen, B. & Orkin, F. Acquiring medical services for individuals with mental retardation in community-based housing facilities. Appl. Nurs. Res. 18, 155–159 (2005).

190

Dubin, S. When the patient suffers: optimization of transitions between care facilities. Geriatr. Nurs. 28, 298–300 (2007).

191

Davies, H., Rennick, J. & Majnemer, A. Transition from pediatric to adult health care for young adults with neurological disorders: parental perspectives. Can. J. Neurosci. Nurs. 33, 32–39 (2011).

192

Bindels-de Heus, K. G., van Staa, A., van Vliet, I., Ewals, F. V. & Hilberink, S. R. Transferring young people with profound intellectual and multiple disabilities from pediatric to adult medical care: parents’ experiences and recommendations. Intellect. Dev. Disabil. 51, 176–189 (2013).

193

Stein, G. L. & Kerwin, J. Disability perspectives on health care planning and decision-making. J. Palliat. Med. 13, 1059–1064 (2010).

194

Baas, M. et al. Building treasures for rare disorders. Eur. J. Med. Genet. 58, 11–13 (2015).

195

Cacioppo, C. N., Conway, L. J., Mehta, D., Krantz, I. D. & Noon, S. E. Attitudes about the use of internet support groups and the impact among parents of children with Cornelia de Lange syndrome. Am. J. Med. Genet. C Semin. Med. Genet. 172, 229–236 (2016).