Proximal Deletion of 6q Overlapping with Toriello-Carey Facial Phenotype: Prenatal Findings, Clinical Course, Differential Diagnosis, and Review

Abstract

Proximal deletion of 6q is a relatively rare chromosomal abnormality. Reported patients have deletions of different sizes but share partial overlap and present with similar clinical features, and some of them were described prior to the introduction of chromosome microarrays. We describe a male patient with prenatal sonographic findings of nuchal edema, intrauterine growth restriction, renal pelvis dilatation, and oligohydramnios. At birth, facial dysmorphism, retro/micrognathia, a short and wide neck as well as cardiovascular and renal anomalies were noted. His clinical evolution has been marked by failure to thrive, severe developmental delay, and cognitive impairment. The diagnosis of Toriello-Carey syndrome (TCS) was based on his “gestalt.” aCGH identified a de novo proximal deletion of 17 Mb in 6q (6q12q14.3). Deletion 6q13q14 seems to be responsible for the main facial features and should be considered within the differential diagnosis of TCS.

Prevalence of monogenic bone disorders in a Dutch cohort of atypical femur fracture patients

“…Deletions in this region have been associated with the 6q12-14.3 deletion syndrome, involving a diversity of clinical features that matched the phenotype of our patient such as intellectual disability, congenital deformities, cardiovascular and renal abnormalities, hearing loss, and hypotonia, but not limb deformities or fragility fractures. (59)(60)(61) TENT5A is responsible for autosomal recessive OI, but haploinsufficiency has not been documented as one of its dysfunction mechanisms and our patient lacked other signs of OI. (62) Van Esch and colleagues reported three patients with 6q deletion syndrome and developmental delay, mild dysmorphism, and signs of lax connective tissue, sharing a 3.7 Mb deleted region overlapping with that in our patient, which includes COL12A1.…”

Prevalence of Monogenic Bone Disorders in a Dutch Cohort of Atypical Femur Fracture Patients

“…Deletions in this region have been associated with the 6q12‐14.3 deletion syndrome, involving a diversity of clinical features that matched the phenotype of our patient such as intellectual disability, congenital deformities, cardiovascular and renal abnormalities, hearing loss, and hypotonia, but not limb deformities or fragility fractures. ( 59‐61 ) TENT5A is responsible for autosomal recessive OI, but haploinsufficiency has not been documented as one of its dysfunction mechanisms and our patient lacked other signs of OI. ( 62 ) Van Esch and colleagues reported three patients with 6q deletion syndrome and developmental delay, mild dysmorphism, and signs of lax connective tissue, sharing a 3.7 Mb deleted region overlapping with that in our patient, which includes COL12A1 .…”

6q13q14.3 Microdeletion Syndrome with Severe Hypotonia and Facial Dysmorphism: Genotype–Phenotype Correlation

“…Catena et al did genotype-phenotype correlation of 24 patients with 6q deletion described in 17 previous studies. 5 Craniofacial features and DD were presented in all. Corpus callosum agenesis was noted in one patient.…”

“…Deletion of chromosome 6q is a rare chromosomal abnormality and characterized by FD such as upslanting palpebral fissures, short nose and anteverted nares, a thin upper lip, smooth long philtrum, and large earlobes, failure to thrive, feeding difficulties, DD, cognitive impairment and multiple anomalies, most common is cardiac defects and urogenital anomalies. 4,5 The rarity of this syndrome results in diagnostic delays especially in patients without cardiac malformation or characteristic facial features.…”