sparse hair

Coats Plus Syndrome

Clinical Characteristics
Ocular Features: 

Retinal telangiectasia and exudates (Coats disease) occur in association with intracranial cysts, calcifications and extraneurologic manifestations in this condition.  Coats disease lesions may also occur in Labrune syndrome (614561) and, of course, in isolation.

Whereas simple Coats disease almost exclusively occurs unilaterally and in males, both sexes and both eyes may have Coats retinal lesions in this syndrome.

Systemic Features: 

As a result of intracranial calcifications, leukodystrophy and brain cysts, patients have a variety of neurologic signs including spasticity, ataxia, dystonia, cognitive decline, and seizures.  Vascular ectasias may also occur throughout the body such as the intestines, stomach, and in the liver increasing the risk of GI bleeding and portal hypertension with anemia and thrombocytopenia.  Some individuals have sparse hair, abnormal pigmentation of the skin, and dysplastic nails as well. 

Some extraretinal features are also found in patients with dyskeratosis congenita (127550), and in Labrune syndrome (614561).

Genetics

This autosomal recessive pleotropic disorder results from compound heterozygous mutations in the CTC1 gene (17p13.1).  Several patients with mutations in STN1 have also been reported.

Most cases of simple Coats disease occur sporadically.  No associated locus or mutation has been found.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment for the general condition has been reported.  Specific treatment for the retinal vascular and brain lesions might be of benefit.  Physical therapy and special education should be considered in selected patients.

References
Article Title: 

Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects. J Exp Med. 2016 Jul 25;213(8):1429-40

Simon AJ, Lev A, Zhang Y, Weiss B, Rylova A, Eyal E, Kol N, Barel O, Cesarkas K, Soudack M, Greenberg-Kushnir N, Rhodes M, Wiest DL, Schiby G, Barshack I, Katz S, Pras E, Poran H, Reznik-Wolf H, Ribakovsky E, Simon C, Hazou W, Sidi Y, Lahad A, Katzir H, Sagie S, Aqeilan HA, Glousker G, Amariglio N, Tzfati Y, Selig S, Rechavi G, Somech R. Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects. J Exp Med. 2016 Jul 25;213(8):1429-40.

PubMed ID: 
27432940

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Anderson BH, Kasher PR, Mayer J, Szynkiewicz M, Jenkinson EM, Bhaskar SS, Urquhart JE, Daly SB, Dickerson JE, O'Sullivan J, Leibundgut EO, Muter J, Abdel-Salem GM, Babul-Hirji R, Baxter P, Berger A, Bonafe L, Brunstom-Hernandez JE, Buckard JA, Chitayat D, Chong WK, Cordelli DM, Ferreira P, Fluss J, Forrest EH, Franzoni E, Garone C, Hammans SR, Houge G, Hughes I, Jacquemont S, Jeannet PY, Jefferson RJ, Kumar R, Kutschke G, Lundberg S, Lourenco CM, Mehta R, Naidu S, Nischal KK, Nunes L, Ounap K, Philippart M, Prabhakar P, Risen SR, Schiffmann R, Soh C, Stephenson JB, Stewart H, Stone J, Tolmie JL, van der Knaap MS, Vieira JP, Vilain CN, Wakeling EL, Wermenbol V, Whitney A, Lovell SC, Meyer S, Livingston JH, Baerlocher GM, Black GC, Rice GI, Crow YJ. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nat Genet. 2012 Jan 22;44(3):338-42.

PubMed ID: 
22267198

Developmental Delay with Short Stature, Dysmorphic Features, and Sparse Hair

Clinical Characteristics
Ocular Features: 

Patients may have downward-slanting lid fissures, hypertelorism, epicanthal folds, and sparse eyebrows and eyelashes.

Systemic Features: 

Patients have scaphocephaly with or without craniosynostosis and facial dysmorphism with a depressed nasal bridge and micrognathia.  Short stature, sparse hair, and developmental delay are characteristic.  Hypoplastic toenails and dental anomalies are present.  Brain imaging may show Dandy-Walker malformations and cerebellar vermis hypoplasia.  The kidneys may have focal interstitial nephritis and there may be intermittent hematuria and proteinuria in the presence of otherwise normal renal function.  Cardiac septal defects have been noted.

Genetics

Homozygous mutations in the DPH1 gene (17p13.3) are responsible for this disorder.  Two families have been reported with this condition. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

Matching two cohorts validates DPH1 as a gene responsible for autosomal recessive intellectual disability with short stature, craniofacial, and ectodermal anomalies

Loucks CM, Parboosingh JS, Shaheen R, Bernier FP, McLeod DR, Seidahmed MZ, Puffenberger EG, Ober C, Hegele RA, Boycott KM, Alkuraya FS, Innes AM. Matching two independent cohorts validates DPH1 as a gene responsible for autosomal recessive intellectual disability with short stature, craniofacial, and ectodermal anomalies. Hum Mutat. 2015 Oct;36(10):1015-9.

PubMed ID: 
26220823

Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families

Alazami AM, Patel N, Shamseldin HE, Anazi S, Al-Dosari MS, Alzahrani F, Hijazi H, Alshammari M, Aldahmesh MA, Salih MA, Faqeih E, Alhashem A, Bashiri FA, Al-Owain M, Kentab AY, Sogaty S, Al Tala S, Temsah MH, Tulbah M, Aljelaify RF, Alshahwan SA, Seidahmed MZ, Alhadid AA, Aldhalaan H, AlQallaf F, Kurdi W, Alfadhel M, Babay Z, Alsogheer M, Kaya N, Al-Hassnan ZN, Abdel-Salam GM, Al-Sannaa N, Al Mutairi F, El Khashab HY, Bohlega S, Jia X, Nguyen HC, Hammami R, Adly N, Mohamed JY, Abdulwahab F, Ibrahim N, Naim EA, Al-Younes B, Meyer BF, Hashem M, Shaheen R, Xiong Y, Abouelhoda M, Aldeeri AA, Monies DM, Alkuraya FS. Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. Cell Rep. 2015 Jan 13;10(2):148-61.

PubMed ID: 
25558065
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