Abstract
Disclosure: P. Jaisinghani: Consulting Fee; Self; Novo Nordisk. J. Pappas: None. We present a 35 year old female with cataracts, generalized seizures and oligodontia, referred to us for hair loss and elevated TSH. For over 10 years, patient had a diffuse hair loss which progressed to a focal patch of hair loss in the setting of prior use of keppra and seborrheic dermatitis. Patient has regular menses, and no symptoms of hyper/hypothyroidism or family history of thyroid disease. Patient established care with dermatology and scalp biopsy noted early androgenetic alopecia. Physical exam was notable for short stature, height 4'11, 98 lbs, BMI 19.8 kg/m², progeric appearance, facial hyperpigmented spot, hair thinning, palpable thyroid R>L. Laboratory evaluation included TSH 6.150 (0.450 - 4.500 uIU/mL), DHEAS 263 (84.8 - 378.0 ug/dL), total testosterone 15 (10 - 55 ng/dL), FSH 6.6 (Follicular phase 3.5 - 12.5 mIU/mL), LH 7.6 (Follicular phase 2.4 - 12.5 mIU/mL), estradiol 83 (Follicular phase 12.5 - 166.0 pg/mL). Thyroid US demonstrated smaller than average size left lobe measuring 2.93 cm x 0.84 cm x 1.36cm vs right lobe measured 4.34 cm x 0.90 cm x 1.62. Labs noted TSH 5.690 (0.450 - 4.500 uIU/mL), establishing subclinical hypothyroidism and negative thyroid antibodies. Clinical genetics evaluation included trio exome sequencing which revealed a de novo pathogenic variant p.(Ser54Leu) (TCG>TTG): c.161 C>T in exon 1 of the MAF gene (NM_005360.4) which establishes the diagnosis of a Ayme- Gripp syndrome (AGS). AGS is characterized by a triad of cataract, sensorineural hearing loss, and characteristic facial features in combination with neurodevelopmental abnormalities. 21 affected individuals from 19 families have been reported with AGS. Clinical features in our case characteristic of AGS included short stature, brachycephaly, midface hypoplasia, long philtrum and premature hair loss. Hypothyroidism was identified in childhood in 3/15 identified individuals who responded to thyroid hormone replacement therapy. For this patient, we will monitor thyroid function tests every 3-6 months and monitor for symptoms of hypothyroidism. Patient has been referred to cardiology and nephrology, and will continue to follow with genetics and dermatology. Our case further establishes the association of hypothyroidism with AGS. Our case demonstrates the value of expanding the differential of endocrinopathies to rare genetic conditions which are currently identifiable by clinically available genomic tests. Presentation: 6/1/2024