New Rare syndromes: October-November 2014

In Uncategorized by Cameron

View the September-October new syndromes list here.

New syndrome of enterocolitis and autoinflammation caused by mutations in NLRC4

Two articles described a previously unreported syndrome featuring neonatal-onset enterocolitis, periodic fever, and fatal or near-fatal episodes of auto-inflammation in two families. The disease is caused by a de novo gain-of-function mutation in NLRC4 in one family (three patients), and by a de novo missense mutation in NLRC4 in the other family (one patient).


Novel syndrome of CTLA4 haploinsufficiency with autoimmune infiltration disease in four unrelated families

The authors identified germline heterozygous mutations in CTLA4 in subjects with severe immune dysregulation from four unrelated families. Patients exhibited lymphocytic infiltration of target organs as well as progressive loss of circulating B cells.


Two new syndromes of developmental delay linked to haploinsufficiency of SETBP1 and truncations of ZMYND11

The authors identified new clinical subtypes of pediatric disease and the genes responsible. These genetic changes include haploinsufficiency of SETBP1 associated with intellectual disability and loss of expressive language and truncations of ZMYND11 in individuals with autism, aggression and complex neuropsychiatric features.


Microcephalic primordial dwarfism compatible with Seckel syndrome caused by mutations in CENPE in two siblings

The authors described novel compound heterozygous variants in CENPE in two siblings who exhibit a profound microcephalic primordial dwarfism associated with developmental delay, simplified gyri and other isolated abnormalities.


Intrauterine growth restriction, short stature, and early-adulthood-onset diabetes associated with a variant in CDKN1C

The authors investigated a familial disorder characterized by intrauterine growth restriction, short stature, and early-adulthood-onset diabetes. Whole exome sequencing of 15 affected and 26 unaffected DNA samples from a six-generation pedigree revealed a novel mutation in CDKN1C.


Novel autosomal recessive intellectual disability syndrome identified in six patients from northern Finland

The authors identified six patients presenting with a strikingly similar clinical phenotype of profound syndromic intellectual disability of unknown etiology. All patients lived in the same village. Extensive genealogical work revealed that the healthy parents of the patients were all distantly related to a common ancestor from the 17th century, suggesting autosomal recessive inheritance. In addition to intellectual disability, the clinical features included hypotonia, strabismus, difficulty to fix the eyes to an object, planovalgus in the feet, mild contractures in elbow joints, interphalangeal joint hypermobility and coarse facial features that develop gradually during childhood. The clinical phenotype did not fit any known syndrome. Further studies are needed to unambiguously identify the underlying genetic defect.


A syndromic form of Pierre Robin sequence is caused by 5q23 deletions encompassing FBN2 and PHAX

Pierre Robin sequence is an etiologically distinct subgroup of cleft palate. The authors defined a region of overlap among four de novo deletions and one mother-son inherited deletion associated with at least one component of Pierre Robin sequence. Commonly associated anomalies were talipes equinovarus, finger contractures and crumpled ear helices. The strongest candidate genes were FBN2 and PHAX.