Compartilhar
Informação da revista
Vol. 99. Núm. 5.
Páginas 749-752 (1 setembro 2024)
Compartilhar
Compartilhar
Baixar PDF
Mais opções do artigo
Visitas
2095
Vol. 99. Núm. 5.
Páginas 749-752 (1 setembro 2024)
Letter - Clinical
Acesso de texto completo
Nail dysplasia and digital hypoplasia ‒ Coffin-Siris syndrome
Visitas
2095
Alba Navarro-Bielsaa,
Autor para correspondência
anavarrobi@salud.aragon.es

Corresponding author.
, Daniel Ruiz Ruiz-de-Larramendizb, Pilar Abenia-Usónb, Tamara Gracia-Cazañaa, Yolanda Gilabertea
a Dermatology Service, Miguel Servet University Hospital, Zaragoza, Spain
b Pediatric Service, Miguel Servet University Hospital, Zaragoza, Spain
Este item recebeu
Informação do artigo
Texto Completo
Bibliografia
Baixar PDF
Estatísticas
Figuras (1)
Tabelas (1)
Table 1. Differential diagnosis of Coffin-Siris syndrome.
Texto Completo
Dear Editor,

Coffin-Siris syndrome is a clinical and genetically heterogeneous congenital disorder characterized by coarse facial features, intellectual disability, hypoplasia of the distal phalanges, and aplasia or hypoplasia of the nails.

A 7-month-old boy was seen by the dermatology service for a congenital nail disorder. The toddler had been diagnosed with mega cisterna magna, a permeable oval foramen, right renal hypoplasia, and slightly delayed psychomotor development with a risk of impaired cognitive development. Physical examination revealed dysplasia of all nails and anonychia or micronychia of the 3rd, 4th, and 5th toes and the 4th and 5th fingers (Fig. 1A‒B). The patient had characteristic facial features with a broad nasal bridge, wide mouth, and thick upper and lower lips.

Fig. 1.

Clinical pictures with nail changes (A‒B) and radiographic (C‒D) images showing hypoplasia of the distal phalanges of the 2nd, 3rd, 4th, and 5th fingers, absent distal phalanges in the 2nd, 3rd, 4th, and 5th toes, and distal phalanx hypoplasia of the 1st toe.

(0.47MB).

Radiography of the hands and feet revealed hypoplasia of the distal phalanges of the 2nd, 3rd, 4th, and 5th fingers of both hands, absent distal phalanges on the 2nd, 3rd, 4th, and 5th toes of both feet and hypoplasia of the distal phalanx of the 1st toe on both feet (Fig. 1C‒D).

A genetic study was performed on suspicion of Coffin-Siris syndrome and revealed a heterozygous de novo mutation in ARID1A (c.2988 + 1 G > A) associated with Coffin-Siris syndrome type 2 (autosomal dominant), OMIM 614607.

Coffin-Siris syndrome is a rare congenital malformation syndrome, of which fewer than 200 cases have been described, and is caused by mutations in several genes encoding components of the BRG1/BRM Associated Factor (BAF) complex, with 12 different subtypes depending on the gene mutation, including (from highest to lowest proportion of cases) ARID1B, SMARCB, SMARCA4, ARID1A, SOX11, SMARCE1, and PHF6.1,2 The BAF complex is an ATP-dependent chromatin remodeler and is involved in transcription, cell differentiation, and DNA repair, a phenotype-genotype correlation is emerging because mutations in BAF, have been related to abnormalities of the hair, nails and fingers. It is a clinically heterogeneous syndrome, the main signs of which include mild to severe cognitive or developmental delay, coarse facial features, and hypoplasia or aplasia of the nail and the distal phalanx of the 5th and occasionally additional fingers (toes are usually affected in individuals with multiple finger involvement). These distinctive facial features include thick eyebrows and long eyelashes, wide nasal bridge, wide mouth with thick, everted upper and lower lips, and abnormal position of the pinna. Other minor features include hypotonia, hirsutism or hypertrichosis, and sparse scalp hair, short stature, feeding difficulties, slow growth, and congenital anomalies including microcephaly, ophthalmological manifestations, and cardiac, gastrointestinal, genitourinary, and nervous system malformations.1,3,4

The differential diagnosis includes Brachymorphism-Onychodysplasia-Dysphalangism (BOD) syndrome, mosaic trisomy 9, DOORS (Deafness, Onychodystrophy, Osteodystrophy, Intellectual Disability) syndrome, fetal hydantoin/phenytoin embryopathy, fetal alcohol spectrum disorders, Mabry syndrome, Cook syndrome, Zimmermann-Laband syndrome, nail-patella syndrome, and Iso-Kikuchi syndrome. Table 1 summarizes clinical similarities and differences of these differential diagnoses with respect to Coffin Siris syndrome, the definitive diagnosis of which is genetic.3

Table 1.

Differential diagnosis of Coffin-Siris syndrome.

Syndrome  Clinical features similar to Coffin-Siris syndrome  Clinical features distinct from Coffin Siris syndrome  Diagnosis 
Brachymorphism-onychodysplasia-dysphalangism (BOD)  Tiny dysplastic nails, short fifth fingers, wide mouth with broad nose, mild intellectual deficits  ‒  Suggested that Coffin-Siris syndrome and BOD syndrome are allelic variants 
Mosaic trisomy 9  Hypoplasia of the 5th digits, facial features, hirsutism, congenital cardiac, urogenital and neurologic anomalies  Skeletal anomalies and pigmentary mosaic skin lesions along Blaschko lines  Karyotype 
DOORS  Hypoplastic terminal phalanges and/or nail anomalies, neurologic abnormalities, mild-to-severe intellectual disability  Deafness, osteodystrophy, and seizures  Biallelic pathogenic variants in TBC1D24. Autosomal recessive 
Fetal hydantoin/phenytoin embryopathy  Small nails with hypoplasia of distal phalanges, dysmorphic facial features, digitalized thumbs, growth retardation, cognitive disabilities, cardiac anomalies  Microcephaly, ocular defects, oral clefts, umbilical and inguinal hernias, and hypospadias  History of phenytoin exposure during gestation 
Fetal alcohol spectrum  Small nails, prenatal and postnatal growth retardation, dysmorphic facial features, cognitive disabilities, neurologic, urogenital, and ocular abnormalities  Musculoskeletal and auditory system abnormalities  History of fetal alcohol exposure 
Mabry  Hypoplastic 5thdigits, delayed development, coarse facial features, hypotonia, congenital heart defects  Elevated serum concentrations of alkaline phosphatase, seizures, cleft palate, megacolon, anorectal malformations  Biallelic pathogenic variants in PIGV. Autosomal recessive 
CookHypo/anonychia, small or absent distal phalanges and thumb digitalizationNo facial dimorphism. Cook syndrome is considered a clinical form of type B brachydactyly (hypoplasia or aplasia of the terminal parts of fingers 2–5)Mutations in ROR2 gene (9q22). 
Autosomal dominant 
Zimmermann-LabandAbsence or hypoplasia of the fingernails or terminal phalanges of the hands and feet and coarse facial features.  Gingival fibromatosisGenetic basis is unknown. Autosomal dominant inheritance has been proposed
Hypertrichosis, cognitive disabilities 
Nail patellaNail hypoplasia or aplasia, renal and ocular abnormalitiesPatellar dysostosis, elbow dysplasia, presence of iliac hornsMutations in the LMX1B gene. 
Autosomal dominant 
Iso-KikuchiAnonychia or dysplasia of the nail of the index finger accompanied by underlying bone abnormalitiesRarely associated with other conditionsGenetic basis is unknown. 
Autosomal dominant inheritance has been proposed 

DOORS, Deafness, Onychodystrophy, Osteodystrophy, Intellectual Disability.

The management of patients diagnosed with Coffin-Siris syndrome is symptomatic and consists of occupational, physical, and feeding therapies, including nutritional supplementation and/or gastrostomy tube placement as needed. The prognosis depends on the extent of involvement.

It will be necessary for a yearly evaluation by different specialists, like otorhinolaryngology, ophthalmology, and neurology y/o digestive to assess developmental progress and therapeutic and educational interventions.

In conclusion, Coffin-Siris syndrome is a clinically heterogeneous syndrome. While nail involvement and hypoplasia of the distal phalanges can be among the less serious clinical signs, dermatologists should be familiar with these manifestations, which are often key to establishing the diagnosis.

Financial support

None declared.

Authors’ contributions

Alba Navarro-Bielsa: The study concept and design; data collection, or analysis and interpretation of data; writing of the manuscript or critical review of important intellectual content; data collection, analysis and interpretation; effective participation in the research guidance; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; final approval of the final version of the manuscript.

Daniel Ruiz Ruiz-de-Larramendiz: The study concept and design; data collection, or analysis and interpretation of data; writing of the manuscript or critical review of important intellectual content; data collection, analysis and interpretation; effective participation in the research guidance; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; final approval of the final version of the manuscript.

Pilar Abenia-Usón: The study concept and design; data collection, or analysis and interpretation of data; data collection, analysis and interpretation; effective participation in the research guidance; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; final approval of the final version of the manuscript.

Tamara Gracia-Cazaña: The study concept and design; data collection, or analysis and interpretation of data; writing of the manuscript or critical review of important intellectual content; data collection, analysis and interpretation; effective participation in the research guidance; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; final approval of the final version of the manuscript.

Yolanda Gilaberte: The study concept and design; data collection, or analysis and interpretation of data; writing of the manuscript or critical review of important intellectual content; data collection, analysis and interpretation; effective participation in the research guidance; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; final approval of the final version of the manuscript.

Conflicts of interest

None declared.

References
[1]
F. Sekiguchi, Y. Tsurusaki, N. Okamoto, K.W. Teik, S. Mizuno, H. Suzumura, et al.
Genetic abnormalities in a large cohort of Coffin-Siris syndrome patients.
J Hum Genet., 64 (2019), pp. 1173-1186
[2]
T. Kosho, N. Okamoto, Coffin-Siris Syndrome International Collaborators..
Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A.
Am J Med Genet C Semin Med Genet., 166C (2014), pp. 262-275
[3]
S. Schrier Vergano, G. Santen, D. Wieczorek, B. Wollnik, N. Matsumoto, M.A. Deardorff.
Coffin-Siris Syndrome.
GeneReviews® [Internet], pp. 1993-2020
[4]
P. Levy, M. Baraitser.
Coffin-Siris syndrome.
J Med Genet., 28 (1991), pp. 338-341

Study conducted at the Hospital Miguel Servet, Zaragoza, Spain.

Copyright © 2024. Sociedade Brasileira de Dermatologia
Baixar PDF
Idiomas
Anais Brasileiros de Dermatologia (Portuguese)
Opções de artigo
Ferramentas
en pt
Cookies policy Política de cookies
To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.