Cleft Palate, Psychomotor Retardation, and Distinctive Facial Features

Clinical Characteristics

Ocular Features:

The facial dysmorphism is present at birth together with the cleft palate. Downslanting lid fissures, widely spaced eyes, and ptosis may be present. Eyebrows have been described as sparse in one patient. Strabismus and ocular apraxia are present in some children.

Systemic Features:

Three patients have been reported, one of whom also had a second deletion in a gene implicated in the Kabuki syndrome. This individual had hypertrichosis and synophyrys whereas the others had sparse eyebrow and temporal hair. The teeth are malformed with some conically shaped and widely spaced. The forehead is prominent and the fingers are tapered and brachydactylous with 5^th finger clinodactyly.

There are significant delays in achieving developmental milestones. Hypotonia has been described. Speech and walking in particular may be delayed for several years. Physical growth may be delayed as well. A variety of brain anomalies have been seen in some but not all individuals. Hypospadius and cryptorchidism have been described. All children reported have palatal anomalies.

Genetics

Heterozygous mutations in the KDM1A gene have been identified in two patients. In another report a single patient had an out-of-frame 3-nucleotide deletion in the ANKRD11 gene (as sometimes found in Kabuki syndrome) plus a mutation in the KDM1A gene.

Treatment

Treatment Options:

No treatment is known.

References

Article Title:

Gene discovery for Mendelian conditions via social networking: de novo variants in KDM1A cause developmental delay and distinctive facial features [1]

Chong JX, Yu JH, Lorentzen P, Park KM, Jamal SM, Tabor HK, Rauch A, Saenz MS, Boltshauser E, Patterson KE, Nickerson DA, Bamshad MJ. Gene discovery for Mendelian conditions via social networking: de novo variants in KDM1A cause developmental delay and distinctive facial features. Genet Med. 2015 Dec 10. doi: 10.1038/gim.2015.161. [Epub ahead of print].

PubMed ID:

26656649

De novo ANKRD11 and KDM1A gene mutations in a male with features of KBG syndrome and Kabuki syndrome [2]

Tunovic S, Barkovich J, Sherr EH, Slavotinek AM. De novo ANKRD11 and KDM1A gene mutations in a male with features of KBG syndrome and Kabuki syndrome. Am J Med Genet A. 2014 Jul;164A(7):1744-9.

PubMed ID:

24838796