Autosomal recessive disease linked to at least two loci. Increased frequency in eastern Pennsylvania Amish.

Synopsis

 acromelic dwarfism (short-limb dwarfism identifiable at birth - average adult height=109 to 152 cm)
 ectodermal dysplasia
 oral anomalies

• partial harelip (fusion of the upper lip to the gingival margin)
• defect in alveolar ridge
• neonatal teeth
• hypodontia
• delayed eruption
• multiple frenula
• abnormally shaped and microdontic teeth
• congenitally missing teeth

 cardiac anomalies

• atrial septal defect
• single atrium
• other cardiac malformations (congenital heart defects)

 thoracic parietal anomalies

• narrow chest
• pectus carinatum
• short, poorly developed ribs

 genital anomalies

• epispadias
• hypospadias
• cryptorchidism

 limb anomalies

• low iliac wings
• spur-like projections at medialateral aspect of acetabula
• centrifugal shortening of limbs
• fusion of capitate and hamate
• genu valgum
• short, thickened tubular bones
• difficulty forming a fist
• postaxial polydactyly
• cone-shaped epiphyses of phalanges 2 to 5
• talipes equinovarus
• postaxial polydactyly fingers/toes
• nail dysplasia
• dandy-Walker malformation

 renal anomalies

• glomerulopathy with nephrotic syndrome

 hepatic anomalies

• paucity of bile ducts progressing to cirrhosis (#12100513#)

Association

 hydrometrocolpos (not linked to chromosome arm 4p or 20p) (#15054850#)
 thymic hypoplasia (#12538281#)
 nephronophtisis (#9502561#)

Cytogenetics

 segmental uniparental disomy of chromosome 4

Etiology

 mutations in EVC gene at 4p16 (MIM.604831)
 mutations in EVC2 gene at 20p (MIM.607261) (#12571802#, #12468274#)
 other loci

Differential diagnosis

 short rib-polydactyly syndromes