DVL1

Clinical Characteristics

Robinow syndrome (RS) is a rare type of syndrome of short stature with predominent mesomelic shortening. It was first described by Robinow et al. (1969) in a family with several individuals showing an autosomal dominant inheritance pattern. The characteristic features are peculiar facies including broad forehead, midface hypoplasia, hypertelorism, short upturned nose, and a broad mouth, known collectively as 'fetal facies', mesomelic limb shortening, hypoplastic genitalia, hydronephrosis, urinary tract infections, skeletal and vertebral anomalies.
Autosomal dominant forms have some unique and some overlapping clinical features with autosomal recessive forms.
Macrocephaly, large anterior fontanelle, delayed closure of fontanelle, prominent eyes, crowding of teeth, bifid tongue, absent uvula, dental malocclusion are some features in both forms.

In autosomal dominant form, short stature is observed in few individuals and it persists into adulthood but is typically not severe.
Genital anomalies like hypoplastic genitalia are apparent at birth for males and females. Both puberty and fertility are normal and affected females can carry pregnancies to term.
Cardiac and renal abnormalities occur in a minority of individuals.
Mesomelia is seen but may be subtle and there may be abnormalities of pronation and supination. Brachydactyly is also common.
Cognitive function is usually normal though mild delay can occur in a minority.
The main differentiating features of dominant forms from recessive forms include absence of rib fusions, and vertebral segmentation defects in the former.
Umbilical hernia and supernumerary teeth are two specific features exclusively reported in dominant forms.

The characteristic radiological features of individuals with DVL1 sequence variations include typical metacarpophalangeal pattern (hypoplastic distal and middle phalanges, bifid distal phalanges, modeling deformity of metacarpals), mesomelia, absence of rib fusion, less frequent vertebral defects, and age-dependent progressive generalized osteosclerosis with or without undertubulation.

It is a genetically heterogeneous disorder with DVL1 being the commonest cause for causing autosomal dominant (AD) type.