Diagnosis of Van den Ende–Gupta syndrome: Approach to the Marden–Walker‐like spectrum of disorders

Abstract

Marden-Walker syndrome is challenging to diagnose, as there is significant overlap with other multi-system congenital contracture syndromes including Beals congenital contractural arachnodactyly, D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome), Schwartz-Jampel syndrome, Freeman-Sheldon syndrome, Cerebro-oculo-facio-skeletal syndrome, and Van den Ende-Gupta syndrome. We discuss this differential diagnosis in the context of a boy from a consanguineous union with Van den Ende-Gupta syndrome, a diagnosis initially confused by the atypical presence of intellectual disability. SNP microarray and whole exome sequencing identified a homozygous frameshift mutation (p.L870V) in SCARF2 and predicted damaging mutations in several genes, most notably DGCR2 (p.P75L) and NCAM2 (p.S147G), both possible candidates for this child's intellectual disability. We review distinguishing features for each Marden-Walker-like syndrome and propose a clinical algorithm for diagnosis among this spectrum of disorders. © 2016 Wiley Periodicals, Inc.

Inclusion of joint laxity, recurrent patellar dislocation, and short distal ulnae as a feature of Van Den Ende-Gupta syndrome: a case report

“…Another unusual finding in our patients was the bilateral shortness of the distal ulnae. This feature was not mentioned in reviews of VDEGS [ 2 , 3 , 9 ]. However, our literature review revealed that bilateral shortness of the distal ulnae was reported in the original patient of Gupta et al [ 10 ] as well as in the patient reported by Migliavacca et al [ 4 ].…”

“…Our review of the literature revealed that the clinical features of VDEGS may be classified into 3 groups (Table 1 ). “Constant or almost constant” features are seen in 90–100% of reported cases, while “common” features are seen in 40–89% of cases as shown in Table 1 [ 1 – 7 , 9 , 10 ]. “Uncommon” features are seen in less than 40% of cases and these include small scapulae [ 2 , 5 ], bowing of the femoral and humeral shafts [ 2 , 3 ], bowing of the proximal ulna [ 11 ], cleft palate [ 12 ], 2–3 toe syndactyly [ 2 , 3 , 5 ], hydronephrosis [ 3 ], dilatation of the renal pelvis [ 5 ], scaphocephaly [ 5 ], trigonocephaly [ 3 ], speech delay [ 3 ], sacral dimple [ 5 ], various ear abnormalities [ 4 – 7 , 11 ], various eye abnormalities [ 4 , 6 ], cerebellar enlargement [ 7 ], scoliosis [ 4 ], transient hypocalcemia at birth [ 6 ], hypoplastic nails with short or hypoplastic distal phalanges [ 10 ], clinodactyly [ 10 , 11 ], club feet [ 7 , 12 , 13 ], hypoplasia of the glenoid fossa [ 3 , 10 , 13 ], micrognathia [ 5 , 13 ], learning disability [ 7 ], single umbilical artery [ 10 ], laryngeal abnormalities [ 14 ], sensorineural hearing loss [ 1 , 9 ], deviated nasal septum [ 1 , 9 ], hypospadias [ 9 ], atrial septal defect [ 9 ], significant developmental delay [ 9 ], joint laxity [current report], recurrent patellar dislocation [3, current report], and short distal ulnae [4,10, current report].…”

The Hidden Side of NCAM Family: NCAM2, a Key Cytoskeleton Organization Molecule Regulating Multiple Neural Functions

“…Even though Ncam2 is located outside the critical region of chromosome 21, it is believed that an increased expression of NCAM2 could negatively affect the nervous system development due to dosage-related effects. In addition, genetic analyses revealed single nucleotide polymorphisms in NCAM2 gene in patients with abnormal neurodevelopment [ 167 ], Marden–Walker syndrome patients [ 170 ] and Autism Spectrum Disorders [ 23 , 164 , 165 ]. Not only does NCAM2 regulate neuronal polarization and formation of axo-dendritic compartments, but it also interacts with different cytoskeleton components that are linked to autism disorder [ 69 , 70 , 171 , 172 , 173 ].…”

Kaufman oculocerebrofacial syndrome: Novel UBE3B mutations and clinical features in four unrelated patients

“…4) Kaufman oculocerebrofacial syndrome (OMIM 244450) (Kaufman, Rimoin, Prensky, & Sly, ) discussed in the present article. 5) the Marden–Walker spectrum (OMIM 248700) where myopathy and joint contractures are core features (Linder et al, ; Niederhoffer et al, ). 6) Dubowitz syndrome (OMIM 223370) presenting with primordial short stature and microcephaly (Majewski, Michaelis, Moosmann, & Bierich, ).…”