OOA (Old Order Amish)

Inheritance: autosomal recessive
Genes: R272Q


Cleft lip
Cleft palate
Mid-face hypoplasia
Genital anomalies
Hip abduction
Fused eyelids

ECO Syndrome

Clinical Characteristics

General description (for patients):

This is a lethal infantile disorder with multiple malformations of bones, and brain. Infants are usually born prematurely and live only a short time. They may have excess water in the brain and usually have extra digits on the hands and feet. The brain itself has severe malformations. The face appears flattened and often the eyelids are not separated.  Cleft lip and palate are common. The base of the nose appears wide, the arms are bowed and short, and the lower legs are splayed at the hip.  Genitalia, especially in males, are abnormal.  

Medical description:

ECO is a multisystem malformation disorder caused by a mutation in a protein kinase that seems to play a central role in regulating cell proliferation and division.  The disorder is incompatible with life as a result of central nervous system maldevelopment, including hydrocephaly of the lateral ventricles, absence of the third ventricle, diencephalic agenesis, and brainstem malformations.  Birth is usually premature. The mid-face is flattened, the nasal bridge is broad, eyelids may be fused, the ears are low-set, cleft lip and/or palate is often present and the jaw is small.  The upper extremities are short and bowed while the hands have ulnar deviation.  Post-axial polydactyly can be present on all four extremities, and syndactyly is often noted. The hips are abducted and there is often a wide gap between the first and second toes.  Genital anomalies are common, especially among males. Adrenal and pituitary glands are hpoplastic. 


ECO has been described in 6 Amish infants in a familial pattern consistent with autosomal recessive inheritance. This inheritance pattern is confirmed by the finding of a missense mutation, R272Q, homozygous in affected individuals, and heterozygous in the parents. The gene, located on chromosome 6 (6p12.2-p12), encodes intestinal cell kinase (ICK), and the mutation consists of the base substitution c.1305G>A.


No treatment is known


Lethal in the neonate

Ancillary treatments and support:

None available

Specialists and specialty centers:

Pediatrician, Neonatologist


Lahiry, P., Wang, J., Robinson, J.F., Turowec, J.P., Litchfield, D.W., Lanktree, M.B., Gloor, G.B., Puffenberger, E.G., Strauss, K.A., Martens, M.B., Ramsay, D.A., Rupar, C.A., Siu, V., and Hegele, R.A.: A multiplex human syndrome implicates a key role for intestinal cell kinase in development of central nervous, skeletal, and endocrine systems. Am. J. Hum. Genet. 84: 134-147, 2009.  PubMed: 19185282