Failure to thrive, and Polydactyly

Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013).There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, {218330}).For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (OMIM ).

SHORT-RIB THORACIC DYSPLASIA 8 WITH OR WITHOUT POLYDACTYLY; SRTD8 Is also known as srps6|short rib-polydactyly syndrome, type vi

• Short stature
• Failure to thrive
• Depressed nasal bridge
• Hepatomegaly
• Brachydactyly

SOURCES: OMIM MENDELIAN

McKusick-Kaufman syndrome is a very rare, genetic developmental disorder presenting in the neonatal period characterized by genitourinary malformations, polydactyly, and more rarely, congenital heart disease or gastrointestinal malformations.

MCKUSICK-KAUFMAN SYNDROME Is also known as kaufman-mckusick syndrome|hydrometrocolpos-postaxial polydactyly syndrome

• Intellectual disability
• Global developmental delay
• Short stature
• Failure to thrive
• Cleft palate

SOURCES: ORPHANET MENDELIAN

Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is a polymalfomative syndrome characterized by cutaneous capillary malformations, megalencephaly, cortical brain malformations (most distinctively polymicrogyria), abnormalities of somatic growth with body and brain asymmetry, developmental delay, and characteristic facial dysmorphism.

MEGALENCEPHALY-CAPILLARY MALFORMATION-POLYMICROGYRIA SYNDROME Is also known as megalencephaly-cutis marmorata telangiectatica congenita syndrome|macrocephaly-capillary malformation syndrome|mcmtc|mcap|megalencephaly-capillary malformation syndrome|macrocephaly-cutis marmorata telangiectatica congenita syndrome|mcm

• Intellectual disability
• Global developmental delay
• Neoplasm
• Failure to thrive
• Muscular hypotonia

SOURCES: ORPHANET MENDELIAN

BBS11 was diagnosed in members of a single Israeli Bedouin family based on the presence of at least 3 of the following features: obesity, polydactyly, renal anomalies, retinopathy, hypogonadism, and learning disabilities (Chiang et al., 2006).For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (OMIM ).

• Obesity
• Hypogonadism
• Polydactyly
• Abnormality of the kidney
• Retinopathy

SOURCES: OMIM MENDELIAN

Ornithine transcarbamylase deficiency is an X-linked inborn error of metabolism of the urea cycle which causes hyperammonemia. The disorder is treatable with supplemental dietary arginine and low protein diet.Urea cycle disorders are characterized by the triad of hyperammonemia, encephalopathy, and respiratory alkalosis. Five disorders involving different defects in the biosynthesis of the enzymes of the urea cycle have been described: OTC deficiency, carbamyl phosphate synthetase deficiency (OMIM ), argininosuccinate synthetase deficiency, or citrullinemia (OMIM ), argininosuccinate lyase deficiency (OMIM ), and arginase deficiency (OMIM ).

ORNITHINE TRANSCARBAMYLASE DEFICIENCY, HYPERAMMONEMIA DUE TO Is also known as ornithine carbamoyltransferase deficiency|otc deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Ataxia
• Growth delay

SOURCES: ORPHANET OMIM MENDELIAN

Autosomal dominant anomaly characterized by abnormal ovoid shape GRANULOCYTE nuclei and their clumping chromatin. Mutations in the LAMIN B receptor gene that results in reduced protein levels are associated with the disorder. Heterozygote individuals are healthy with normal granulocyte function while homozygote individuals occasionally have skeletal anomalies, developmental delay, and seizures.

• Intellectual disability
• Global developmental delay
• Hypertelorism
• Failure to thrive
• Strabismus

SOURCES: OMIM MESH MENDELIAN

Peroxisomal acyl-CoA oxidase deficiency is a rare neurodegenerative disorder that belongs to the group of inherited peroxisomal disorders and is characterized by hypotonia and seizures in the neonatal period and neurological regression in early infancy.

PEROXISOMAL ACYL-COA OXIDASE DEFICIENCY Is also known as pseudoneonatal adrenoleukodystrophy|pseudo-neonatal adrenoleukodystrophy|pseudo-nald|pseudoadrenoleukodystrophy|straight-chain acyl-coa oxidase deficiency

• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Hypertelorism

SOURCES: MESH ORPHANET OMIM MENDELIAN

NDMSBA is an autosomal recessive neurodevelopmental disorder characterized by infantile onset of progressive microcephaly and spasticity and severe global developmental delay resulting in profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy. Brain imaging may show myelinating abnormalities and white matter lesions consistent with a leukoencephalopathy, as well as structural anomalies, including thin corpus callosum, gyral abnormalities, and cerebral or cerebellar atrophy. Some patients die in early childhood (summary by Falik Zaccai et al., 2017 and Hall et al., 2017).

PLAA-ASSOCIATED NEURODEVELOPMENTAL DISORDER Is also known as plaand

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: OMIM ORPHANET MENDELIAN

CDG2L is an autosomal recessive multisystem disorder apparent from birth or early infancy. It is characterized by poor growth, gastrointestinal and liver abnormalities, delayed psychomotor development, hypotonia, recurrent infections, hematologic abnormalities, increased bleeding tendency, and hyperhidrosis or hyperkeratosis. More variable features include nonspecific dysmorphic facial features and cardiac septal defects. The disorder often results in death in infancy or the first years of life (summary by Rymen et al., 2015).For a general discussion of CDGs, see CDG1A (OMIM ) and CDG2A (OMIM ).

COG6-CGD Is also known as congenital disorder of glycosylation type 2l|cdg syndrome type iil|cdg-iil|cdg2l|congenital disorder of glycosylation type iil|cdgiil|cdg iil

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: OMIM ORPHANET MENDELIAN