WDR35

Clinical Characteristics

Variants in the WDR35 gene are usually associated with Sensenbrenner syndrome (#OMIM 613610, cranioectodermal dysplasia, CED2), and short-rib thoracic dysplasia 7 with or without polydactyly (#OMIM 614091, SRTD7). Defects in this gene have been described in patients with Ellis-van Creveld syndrome (EvC) and Asphyxiating thoracic dystrophy (JATD). These syndromes are inherited in an autosomal recessive manner and belong to a group of disorders collectively known as ciliopathies.

CED2 clinical features include:
•    Short stature
•    Dolichocephaly
•    Craniosynostosis
•    Frontal bossing
•    Full cheeks
•    Low set ears
•    Simple ears
•    Telecanthus
•    Epicanthus
•    Hypertelorism
•    Broad nasal bridge
•    Depressed nasal bridge
•    Everted lower lip
•    Small teeth
•    Widely spaced teeth
•    Short ribs
•    Narrow chest
•    Pectus excavatum
•    Bilateral inguinal hernias
•    Liver abnormalities (hepatomegaly, cholestasis, abnormal echogenicity, abnormal liver function tests)
•    Renal insufficiency (renal cysts, increased echogenicity)
•    Rhizomelic and mesomelic limb shortening
•    Brachydactyly
•    Polydactyly
•    Syndactyly
•    Sparse hair
•    Dysplastic nails
•    Skin laxity
•    Developmental delay (in some patients)
•    Prenatal manifestations (polyhydramnios, hydrops fetalis, increased NT)

SRTD7 clinical features include:
•    Short stature
•    Dolichocephaly
•    Scalp edema
•    Sparse and absent eyebrows
•    Epicanthus
•    Cleft palate
•    Small teeth
•    Missing teeth
•    Fused teeth
•    Hypoplastic lungs
•    Narrow chest
•    Shortened ribs
•    Ascites
•    Hepatic fibrosis
•    Pancreatic dysgenesis
•    Splenic dysgenesis
•    Gastrointestinal malrotation
•    Hypospadias, mild (in males)
•    Polycystic kidneys
•    Limb shortening
•    Brachydactyly
•    Polydactyly
•    Syndactyly
•    Skin edema
•    Dysplastic nails
•    Sparse hair
•    Prenatal manifestations (hydrops fetalis)