MedGen

Spondylo-megaepiphyseal-metaphyseal dysplasia is a rare autosomal recessive skeletal dysplasia characterized by disproportionate short stature with a short and stiff neck and trunk; relatively long limbs that may show flexion contractures of the distal joints; delayed and impaired ossification of the vertebral bodies and the presence of large epiphyseal ossification centers and wide growth plates in the long tubular bones; and numerous pseudoepiphyses of the short tubular bones in hands and feet (summary by Hellemans et al., 2009). [from OMIM]

Any lethal congenital contracture syndrome in which the cause of the disease is a mutation in the ADGRG6 gene. [from MONDO]

Syndromic multisystem autoimmune disease due to Itch deficiency is a rare, genetic, systemic autoimmune disease characterized by failure to thrive, global developmental delay, distinctive craniofacial dysmorphism (relative macrocephaly, dolichocephaly, frontal bossing, orbital proptosis, flattened midface with a prominent occiput, low, posteriorly rotated ears, micrognatia), hepato- and/or splenomegaly, and multisystemic autoimmune disease involving the lungs, liver, gut and/or thyroid gland. [from ORDO]

Ruijs et al. (2003) reported a Moroccan boy with a chromosomal breakage who died of hepatocellular carcinoma at age 17 years. The boy was noted to have growth retardation at age 3 years; at age 7 he was found to have thoracic kyphosis, frontal bossing, and a delayed bone age of approximately 3 years. He underwent surgery for severe bilateral posterior subcapsular cataracts at age 14. Examination at age 15 showed short stature and low weight, with premature graying of scalp hair, small frontotemporal diameter, small deep-set eyes, bulbous nose with high nasal bridge, small upper lip, and micrognathia. In addition, he had thoracic kyphoscoliosis, sloping shoulders, mild pectus excavatum, moderate bilateral contractures of both elbows, bilateral clinodactyly, and pes planus. At age 17, he developed abdominal pain, and ultrasonography revealed a liver mass; biopsy confirmed hepatocellular carcinoma. Because of the advanced stage, no treatment was possible, and he died 2 months later. Although his parents were not known to be consanguineous, they originated from the same small Moroccan village. Lessel et al. (2014) studied 2 brothers from a nonconsanguineous Australian family of European ancestry who exhibited low body weight, micrognathia, triangular face, muscular atrophy, lipodystrophy, bilateral simian creases, delayed bone age, and mild joint restrictions in the fingers and elbows. In addition, both brothers developed early-onset hepatocellular carcinoma, at ages 16 and 14 years, respectively. The older brother died at age 18 from complications of acute fulminant hepatic failure. Analysis of patient tumor biopsies showed strong focal accumulations of cancer biomarkers as well as a high proliferative index compared to healthy liver or to cells from idiopathic hepatocellular carcinoma. [from OMIM]

Turnpenny-Fry syndrome (TPFS) is characterized by developmental delay, impaired intellectual development, impaired growth, and recognizable facial features that include frontal bossing, sparse hair, malar hypoplasia, small palpebral fissures and oral stoma, and dysplastic 'satyr' ears. Other common findings include feeding problems, constipation, and a range of brain, cardiac, vascular, and skeletal malformations (Turnpenny et al., 2018). [from OMIM]

A form of ectodermal dysplasia syndrome characterized by a short stature of prenatal onset, alopecia, ichthyosis, photophobia, ectrodactyly, seizures, scoliosis, multiple contractures, fusions of various bones (particularly elbows, carpals, metacarpals, and spine), intellectual disability, and facial dysmorphism (microdolichocephaly, madarosis, large ears and long nose). ACD syndrome overlaps with ichthyosis follicularis-alopecia-photophobia syndrome. [from ORDO]