Interstitial 1q21.1 Microdeletion Is Associated with Severe Skeletal Anomalies, Dysmorphic Face and Moderate Intellectual Disability

Abstract

We report on a Brazilian patient with a 1.7-Mb interstitial microdeletion in chromosome 1q21.1. The phenotypic characteristics include microcephaly, a peculiar facial gestalt, cleft lip/palate, and multiple skeletal anomalies represented by malformed phalanges, scoliosis, abnormal modeling of vertebral bodies, hip dislocation, abnormal acetabula, feet anomalies, and delayed neuropsychological development. Deletions reported in this region are clinically heterogeneous, ranging from subtle phenotypic manifestations to severe congenital heart defects and/or neurodevelopmental findings. A few genes within the deleted region are associated with congenital anomalies, mainly the RBM8A, DUF1220, and HYDIN2 paralogs. Our patient presents with a spectrum of unusual malformations of 1q21.1 deletion syndrome not reported up to date.

Keywords: Dysmorphic features; Intellectual disability; Microdeletion 1q21.1; Skeletal anomalies.

Fig. 1

A-F The patient at age 9 (A-C) and 19 years (D-F). A small skull, sloping forehead, synophrys, arched eyebrows, a flat nose, prominent ears, large conchae, hypoplastic tragus and lobules, left cleft lip/palate, and a large mouth are shown.

Fig. 2

A-D The hands of the patient showing mild camptodactyly (mainly of 5th finger), short hands, bilateral hypoplasia of the distal phalanges of fingers 2 and 3, with agenesis/hypoplasia of the nails (A, B). X-rays of the hands show gross and misshapen proximal phalanges of fingers 2 and 3, radial clinodactyly of finger 2, hypoplastic distal phalanges of fingers 2 and 3, abnormal ‘bird-like beak’ modeling of the right distal phalanx of finger 2 as well as a small bony fragment distal to the phalanx of finger 3, and a dislocation of the metacarpal phalangeal joints of both thumbs (C, D).

Fig. 3

A-C The feet of the patient showing a wide gap between toes 1 and 2, proximal syndactyly between toes 2 and 3, a short 5th toe (A, B), and marked hypoplasia of median and distal phalanges of toes 3 and 5 with bilateral halluces valgi (C).