Disorder
Microcephalic osteodysplastic primordial dwarfism

Clinical Characteristics

General description (for patients):

Affected infants are small at birth and the skull is small and malformed. The arms and legs are short and may be bowed. The brain is often malformed as well resulting in poor mental functioning. The hips and elbows may be dislocated. Scalp hair and eyebrows are sparse. The brain deformities can lead to early death, sometimes during the newborn period.

Medical description (for healthcare providers):

The skull and facial appearance sometimes causes diagnostic confusion with Seckel bird-headed dwarfism which lacks the limb deformities seen in MOPD. Other skeletal features include hip and elbow dislocations and pelvic deformities. Severe maldevelopment of the brain leads to death sometimes during the neonatal period but a few cases have survived for a year or more. Micrencephaly, microcephaly, absent corpus callosum, agenesis of the vermis, heterotopias, and hypoplasia of the frontal lobes and other structures have been described.

Genetics:

This is an autosomal recessive condition caused by biallelic mutations in RNU4ATAC (2q14.2) encoding U4atac snRNA, a component of a minor spliceosome. It has been found among the Old Order Amish of several Ohio communities.

Management:

No treatment is available for this condition.

Supportive care for respiration and nutrition is the only treatment available.

Prognosis:

The prognosis is poor and death usually occurs before 3 years of age.

Specialists and specialty centers:

The diagnosis is established at birth based on the physical appearance. Pediatricians, neurologists and medical geneticists can be helpful to the diagnosis.

References:

He H, Liyanarachchi S, Akagi K, Nagy R, Li J, Dietrich RC, Li W, Sebastian N, Wen B, Xin B, Singh J, Yan P, Alder H, Haan E, Wieczorek D, Albrecht B, Puffenberger E, Wang H, Westman JA, Padgett RA, Symer DE, de la Chapelle A. Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I. Science. 2011 Apr 8;332(6026):238-40. PubMed PMID: 21474760.

Edery P, Marcaillou C, Sahbatou M, Labalme A, Chastang J, Touraine R, Tubacher E, Senni F, Bober MB, Nampoothiri S, Jouk PS, Steichen E, Berland S, Toutain A, Wise CA, Sanlaville D, Rousseau F, Clerget-Darpoux F, Leutenegger AL. Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA. Science. 2011 Apr 8;332(6026):240-3. PubMed PMID: 21474761.