The Syndrome of Mental Handicap, Cataracts, Muscle Wasting and Skeletal Abnormalities: Report of a Second Case

The cardinal features of Primrose syndrome (MIM 259050) are dysmorphic facial features, macrocephaly, and intellectual disability, as well as large body size, height and weight, and calcified pinnae. A variety of neurological signs and symptoms have been reported including hearing loss, autism, behavioral abormalities, hypotonia, cerebral calcifications, and hypoplasia of the corpus callosum. Recently, heterozygous de novo missense mutations in ZBTB20, coding for a zing finger protein, have been identified in Primrose syndrome patients. We report a boy with intellectual disability carrying two de novo missense mutations in the last exon of ZBTB20 (Ser616Phe and Gly741Arg; both previously unreported). One of them, Ser616Phe, affects an amino acid located in one of the C2H2 zing-fingers involved in DNA-binding and close to other missense mutations already described. Reverse phenotyping showed that this patient presents with classic features of Primrose syndrome (dysmorphic facies, macrocephaly, hearing loss, hypotonia, hypoplasia of the corpus callosum) and, in addition, congenital hypothyroidism. Review of the literature reveals another Primrose syndrome patient with hypothyroidism and thus, this may represent an under recognized component that should be investigated in other patients. © 2016 Wiley Periodicals, Inc.

Section: Introductionmentioning

confidence: 99%

Novel de novo mutations in ZBTB20 in Primrose syndrome with congenital hypothyroidism

Mattioli

Piton

Gérard

et al. 2016

“…In the original report by Primrose (1982), recurrent attacks of bilateral otitis media were described. Later, recurrent otitis media was also reported in three patients (Collacott et al, 1986;Mathijssen et al, 2006;Posmyk et al, 2011). Thus, this phenotype is considered as one of the important complications associated with this syndrome.…”

Section: Discussionmentioning

confidence: 91%

“… Note : Information of the patients reported previously (Battisti et al, ; Carvalho & Speck‐Martins, ; Collacott et al, ; Dalal et al, ; Lindor et al, ; Mathijssen et al, ; Posmyk et al, ; Primrose, ) are included in that reported by Cordeddu et al (). One of the patients reported by Casertano et al () is also included in that by Cordeddu et al ().…”

Section: Discussionmentioning

confidence: 99%

“…Further, the patient also exhibited ankle contractures as a consequence of disuse rather than distal muscle wasting, which is the major feature of this syndrome. The other unique feature observed was the abnormal structure of the cor- Note: Information of the patients reported previously (Battisti et al, 2002;Carvalho & Speck-Martins, 2011;Collacott et al, 1986;Dalal et al, 2010;Lindor et al, 1996;Mathijssen et al, 2006;Posmyk et al, 2011;Primrose, 1982) are included in that reported by Cordeddu et al (2014). One of the patients reported by Casertano et al (2017) is also included in that by Cordeddu et al (2014).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, clinical entity of Primrose syndrome has been established. Other than above mentioned clinical features, recurrent otitis media has been described in the original report (Primrose, 1982) and three additional patients with Primrose syndrome (Collacott et al, 1986;Mathijssen et al, 2006;Posmyk et al, 2011). Overlapping chromosomal deletions in 3q13.31 have been recognized as a clinical entity with developmental delay, muscular hypotonia, and recognizable facial features (Molin et al, 2012;Shimojima, Saito, & Yamamoto, 2009).…”

Section: Introductionmentioning

confidence: 94%

See 2 more Smart Citations

Primrose syndrome associated with unclassified immunodeficiency and a novel ZBTB20 mutation

Yamamoto-Shimojima

Imaizumi

Akagawa

et al. 2019

Primrose syndrome is a congenital malformation syndrome characterized by intellectual disability, developmental delay, progressive muscle wasting, and ear lobe calcification. Mutations in the ZBTB20 gene have been established as being accountable for this syndrome. In this study, a novel de novo ZBTB20 mutation, NM_001164342.2:c.1945C>T (p.Leu649Phe), has been identified through whole exome sequencing (WES) in a female patient presenting a typical Primrose phenotype. Because the present patient exhibited recurrent otitis media, detailed immunological examinations were performed in this study and subnormal immunoglobulin levels were firstly identified in a Primrose patient. Anatomical anomaly of the inner ear has never been reported in this patient and WES data did not include any relevant variants causally linked with the immunologic defect. Thus, there is a possibility of a relation between an unclassified immunodeficiency with selective IgG2 deficiency and Primrose syndrome and this may be the reason of recurrent otitis media frequently observed in Primrose patients. Because subnormal levels of IgG2 in this patient might be caused by an unrelated and still uncharacterized genetic cause, further studies are required to prove the causal link between aberrant ZBTB20 function and immunodeficiency.

Additional features of unique Primrose syndrome phenotype

Carvalho

Speck‐Martins

2011

Primrose syndrome is a unique condition of intellectual disability, dysmorphic facial features, and specific minor abnormalities including large calcified ear auricles. Only six patients have been previously reported. We describe a Brazilian boy with the striking similar facies and the main clinical findings that reinforced the singular phenotype of this rare disorder. The key features of all patients already published were compared. Our young patient has abnormalities that were not observed in preceding reports: nail dysplasia and hyperuricemia.