A novel description of a syndrome consisting of 7q21.3 deletion including DYNC1I1 with preserved DLX5/6 without ectrodactyly: a case report.
BACKGROUND
Chromosomal region 7q21.3 comprises approximately 5.2 mega base pairs that include genes DLX5/6, SHFM1, and DYNC1I1 associated with split hand/split foot malformation 1. So far, there are reports of eight families with deletion of DYNC1I1 and preserved DLX5/6 associated with ectrodactyly. From these families, only three patients did not present ectrodactyly and, unlike our patient, no other cases have been described as having craniofacial dysmorphology, mitral valve prolapse, kyphoscoliosis, inguinal herniae, or personality disorder. There is no designation described in the literature for patients with syndromic manifestations without ectrodactyly, which hinders diagnosis.


METHODS
We report the case of a 44-year-old mestizo (combined European and Amerindian descent) man with a 3191 kilo base pairs deletion and International System for Human Cytogenetic Nomenclature array 7q21.3 (93,389,222-96,579,845)x1. Clinical manifestations included micrognathia, retrognathia, wormian bones, auditory canal stenosis, depressed nasal bridge, epicanthal fold, fullness of upper eyelid, long philtrum, low-set ears, sensorineural hearing loss, kyphoscoliosis, bilateral inguinal herniae, mild mitral valve prolapse, and paranoid personality disorder. His isolated DNA was analyzed using a CytoScan HD Microarray system. Chromosome Analysis Suite software was utilized for the microarray analysis. All copy number changes were determined using the human genome build 19 (hg19/NCBI build 37).


CONCLUSIONS
Cases of deletions within chromosome 7q21.3 that include the split hand/split foot malformation 1 region represent a diagnostic challenge when not presenting ectrodactyly despite being syndromic. Due to the heterogeneity of the region, a better method to group and classify these patients is needed to facilitate their clinical diagnosis. For this purpose, we suggest that patients with 7q21.3 deletion including DYNC1I1 and preserved DLX5/6 without ectrodactyly, accompanied by craniofacial dysmorphology, personality disorder, hearing loss, musculoskeletal disorder, inguinal herniae and/or mitral valve prolapse be referred to by the eponym Ramos-Martínez syndrome.
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras. hramos@unicah.edu.
Héctor M
HM
Ramos-Zaldívar
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Daniel G
DG
Martínez-Irías
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Nelson A
NA
Espinoza-Moreno
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
José S
JS
Napky-Rajo
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Tulio A
TA
Bueso-Aguilar
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Karla G
KG
Reyes-Perdomo
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Jimena A
JA
Montes-Gambarelli
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Isis M
IM
Euceda
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Aldo F
AF
Ponce-Barahona
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Carlos A
CA
Gámez-Fernández
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Wilberg A
WA
Moncada-Arita
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Victoria A
VA
Palomo-Bermúdez
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Julia E
JE
Jiménez-Faraj
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Amanda G
AG
Hernández-Padilla
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Denys A
DA
Olivera
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Kevin J
KJ
Robertson
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Luis A
LA
Leiva-Sanchez
Campus San Pedro y San Pablo, School of Medicine, Universidad Católica de Honduras, San Pedro Sula, Honduras.
Edwin Francisco
EF
Herrera-Paz
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D000328:Adult; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7; D056445:Cytoplasmic Dyneins / Q000235:genetics*; D003638:Deafness; D006801:Humans; D008297:Male; D010259:Paranoid Disorders / Q000235:genetics* / Q000523:psychology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*
C000596072:DYNC1I1 protein, human; C484606:SEM1 protein, human; D046988:Proteasome Endopeptidase Complex; D056445:Cytoplasmic Dyneins
COL1A2; DLX5/6; DSS1; DYNC1I1; Deletion 7q21.3; Ectrodactyly; SGCE; SHFM1; SLC25A13