Facial dysmorphism associated with developmental delay and retinitis pigmentosa in early childhood should prompt a careful family investigation for ataxia and study of ATX2.
Hypoparathyroidism-retardation-dysmorphism (HRD; Sanjad-Sakati Syndrome; Online Mendelian Inheritance in Man [OMIM] #241410) is a rare recessive syndrome predominantly seen on the Arabian Peninsula and characterized by congenital hypoparathyroidism, intrauterine growth retardation, mental retardation, seizures, and a typical facial dysmorphism (prominent forehead, deep-set eyes, and abnormal external ears).(1,2) To date, the same homozygous deletion in TBCE (155-166del) has been reported in all Saudi Arabian patients with HRD(1) as well as in all Saudi Arabian patients with Kenny-Caffey syndrome (OMIM #244460),(1) a syndrome with a phenotype that resembles that of HRD but is characterized by the presence of normal intelligence, late closure of the anterior fontanelle, macrocephaly, and postnatal (rather than prenatal) growth retardation.
BMP4 deletions were detected in two patients: a patient affected with SHORT syndrome and a patient with anterior segment anomalies along with craniofacial dysmorphism and cognitive impairment.
MRXS5 or Pettigrew syndrome was described 20 years ago in a four generation family including nine affected individuals presenting with facial dysmorphism, intellectual disability, Dandy-Walker malformation and inconstant choreoathetosis.
TMCO1 mutations cause craniofacial dysmorphism, skeletal anomalies characterized by multiple malformations of the vertebrae and ribs, and intellectual disability (MIM#614132).
CEDNIK (CErebral Dysgenesis, Neuropathy, Ichthyosis, and Keratoderma) syndrome is a neuroichthyotic syndrome characterized by a constellation of clinical features including severe developmental retardation, microcephaly, and facial dysmorphism.
A filamin A splice mutation resulting in a syndrome of facial dysmorphism, periventricular nodular heterotopia, and severe constipation reminiscent of cerebro-fronto-facial syndrome.
A novel microduplication syndrome involving various-sized contiguous duplications in 17p13.3 has recently been described, suggesting that increased copy number of genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features including facial dysmorphism, developmental delay, and autism spectrum disorder.
A splice site mutation in HERC1 leads to syndromic intellectual disability with macrocephaly and facial dysmorphism: Further delineation of the phenotypic spectrum.
Affected homozygous zebrafish demonstrated congenital defects consistent with the range of PITX2-associated human phenotypes: abnormal development of the cornea, iris and iridocorneal angle; corneal dermoids; and craniofacial dysmorphism.
Affected homozygous zebrafish demonstrated congenital defects consistent with the range of PITX2-associated human phenotypes: abnormal development of the cornea, iris and iridocorneal angle; corneal dermoids; and craniofacial dysmorphism.
Although initial reports of families with ZDHHC9 pathogenic variants suggested a nonsyndromic XLID, more recent reports suggest a syndromic phenotype with facial dysmorphism.
Although no clinical differences between patients carrying EDA1, EDAR, or EDARADD mutations could be identified, patients harboring WNT10A mutations displayed distinctive clinical features (marked dental phenotype, no facial dysmorphism), helping to decide which gene should be first investigated in HED/EDA.
Although severe facial anomalies are common in HPE, all of the patients with ZIC2 mutations had relatively normal faces, suggesting that ZIC2 mutations represent a large proportion of HPE cases without facial malformation.
Autosomal-recessive Schimke immuno-osseous dysplasia (SIOD) characterized by spondyloepiphyseal dysplasia, focal-segmental glomerulosclerosis (FSGS), T-cell immunodeficiency and facial dysmorphism is caused by defects in the SMARCAL1 gene.