RIN2 syndrome: Expanding the clinical phenotype.
Biallelic defects in the RIN2 gene, encoding the Ras and Rab interactor 2 protein, are associated with a rare autosomal recessive connective tissue disorder, with only nine patients from four independent families reported to date. The condition was initially termed MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis), based on the clinical features of the first identified family; however, with the expansion of the clinical phenotype in additional families, it was subsequently coined RIN2 syndrome. Hallmark features of this condition include dysmorphic facial features with striking, progressive facial coarsening, sparse hair, normal to enlarged occipitofrontal circumference, soft redundant and/or hyperextensible skin, and scoliosis. Patients with RIN2 syndrome present phenotypic overlap with other conditions, including EDS (especially the dermatosparaxis and kyphoscoliosis subtypes). Here, we describe a 10th patient, the first patient of Caucasian origin and the oldest reported patient so far, who harbors the previously identified homozygous RIN2 mutation c.1878dupC (p. (Ile627Hisfs*7)). Besides the hallmark features, this patient also presents problems not previously associated with RIN2 syndrome, including cervical vertebral fusion, mild hearing loss, and colonic fibrosis. We provide an overview of the clinical findings in all reported patients with RIN2 mutations and summarize some of the possible pathogenic mechanisms that may underlie this condition. © 2016 Wiley Periodicals, Inc.
Clinical Genetics Unit, Department of Obstetrics and Pediatrics, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
Simonetta
S
Rosato
Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Delfien
D
Syx
Clinical Genetics Unit, Department of Obstetrics and Pediatrics, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.|Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.
Ivan
I
Ivanovski
Clinical Genetics Unit, Department of Obstetrics and Pediatrics, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
Marzia
M
Pollazzon
Clinical Genetics Unit, Department of Obstetrics and Pediatrics, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
Daniela
D
Santodirocco
Anatomic Pathology Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
Loredana
L
De Marco
Department of Internal Medicine, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
Marina
M
Beltrami
Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Bert
B
Callewaert
Clinical Genetics Unit, Department of Obstetrics and Pediatrics, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
Livia
L
Garavelli
Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Fransiska
F
Malfait
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D000293:Adolescent; D000328:Adult; D000483:Alleles; D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics*; D005091:Exons; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011859:Radiography; D013577:Syndrome; D055815:Young Adult
D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; C447829:RIN2 protein, human
RIN2; cutis laxa; progressive facial coarsening; scoliosis; skin hyperextensibility; sparse hair