otopalatodigital syndrome type 2

X-linked dominant disease. Majority of patients are stillborn or die before 5 months of age. Milder manifestations in heterozygous females (broad face, down-slanting palpebral fissures, and cleft palate).

Synopsis

 systemic anomalies

• height
• short stature
• postnatal growth retardation

 craniofacial anomalies

• large anterior fontanel
• prominent forehead
• severe micrognathia
• midface hypoplasia
• low-set ears
• conductive hearing loss
• posteriorly rotated ears
• hypertelorism
• down-slanting palpebral fissures
• flat nasal bridge
• small mouth
• cleft palate

 skeletal anomalies

• respiratory failure
• narrow chest
• pectus excavatum
• thin, wavy clavicles
• wavy, short ribs
• dysharmonic bone maturation
• late closure of large anterior fontanel
• wide sutures
• midface hypoplasia
• vertical clivus
• small mandible
• sclerotic skull base
• wormian bones
• flattened vertebrae
• spondylolysis
• congenital hip dislocation
• hypoplastic ilia
• dense long bones
• radial bowing
• ulnar bowing
• femoral bowing
• tibial bowing
• small (fibular hypoplasia) to absent fibula (fibular agenesis)
• subluxed elbow, wrist, and knee
• flexed fingers, overlapping fingers
• short, broad thumbs
• postaxial polydactyly
• syndactyly
• second finger clinodactyly
• hypoplastic, irregular metacarpals
• tree-frog hands
• short halluces, broad halluces, short and broad halluces
• syndactyly
• nonossified fifth metatarsal
• rocker-bottom feet
• tree-frog feet
• hypoplastic metatarsals (metatarsal hypoplasia)

 opmphalocele
 hypospadias
 cryptorchidism
 hydronephrosis

 cerebral anomalies

• mental retardation
• hydrocephalus

Etiology

 germline mutations in gene FLNA encoding filamin A (MIM.300017)

• as in otopalatodigital syndrome type 1 (type I OPD syndrome or OPD1) (MIM.311300)

Allelic disorder with FLNA mutations

 otopalatodigital syndrome type I (OPD1) (MIM.311300)
 frontometaphyseal dysplasia (FMD) (MIM.305620)
 Melnick-Needles syndrome (MNS) (MIM.309350)
 periventricular heterotopia (MIM.300049)